New evidence for a role of DANCR in cancers: a comprehensive review.

Cancer remains a leading cause of mortality and poses a substantial threat to public health. Studies have revealed that Long noncoding RNA DANCR is a cytoplasmic lncRNA whose aberrant expression plays a pivotal role in various cancer types. Within tumour biology, DANCR exerts regulatory control over crucial processes such as proliferation, invasion, metastasis, angiogenesis, inflammatory responses, cellular energy metabolism reprogramming, and apoptosis. By acting as a competitive endogenous RNA for miRNAs and by interacting with proteins and mRNAs at the molecular level, DANCR contributes significantly to cancer progression. Elevated DANCR levels have also been linked to heightened resistance to anticancer drugs. Moreover, the detection of circulating DANCR holds promise as a valuable biomarker for aiding in the clinical differentiation of different cancer types. This article offers a comprehensive review and elucidation of the primary functions and molecular mechanisms through which DANCR influences tumours.

Novel biallelic SASS6 variants associated with primary microcephaly and fetal growth restriction.

Primary microcephaly is characterized by a head circumference prenatally or at birth that falls below three standard deviations from age-, ethnic-, and sex-specific norms. Genetic defects are one of the underlying causes of primary microcephaly. Since 2014, five variants of the SASS6 gene have been identified as the cause of MCPH 14 in three reported families. In this study, we present the genetic findings of members of a nonconsanguineous Chinese couple with a history of microcephaly and fetal growth restriction (FGR) during their first pregnancy. Utilizing trio whole-exome sequencing, we identified compound heterozygous variants involving a frameshift NM_194292.3:c.450_453del p.(Lys150AsnfsTer7) variant and a splice region NM_194292.3:c.1674+3A>G variant within the SASS6 gene in the affected fetus. Moreover, reverse transcriptase-polymerase chain reaction from RNA of the mother's peripheral blood leukocytes revealed that the c.1674+3A>G variant led to the skipping of exon 14 and an inframe deletion. To the best of our knowledge, the association between FGR and SASS6-related microcephaly has not been reported, and our findings confirm the pivotal role of SASS6 in microcephaly pathogenesis and reveal an expanded view of the phenotype and mutation spectrum associated with this gene.

The promotion of the atrazine degradation mechanism by humic acid in a soil microbial electrochemical system.

The enhancing effects of anodes on the degradation of the organochlorine pesticide atrazine (ATR) in soil within microbial electrochemical systems (MES) have been extensively researched. However, the impact and underlying mechanisms of soil microbial electrochemical systems (MES) on ATR degradation, particularly under conditions involving the addition of humic acids (HAs), remain elusive. In this investigation, a soil MES supplemented with humic acids (HAs) was established to assess the promotional effects and mechanisms of HAs on ATR degradation, utilizing EEM-PARAFAC and SEM analyses. Results revealed that the maximum power density of the MES in soil increased by 150%, and the degradation efficiency of ATR improved by over 50% following the addition of HAs. Furthermore, HAs were found to facilitate efficient ATR degradation in the far-anode region by mediating extracellular electron transfer. The components identified as critical in promoting ATR degradation were Like-Protein and Like-Humic acid substances. Analysis of the microbial community structure indicated that the addition of HAs favored the evolution of the soil MES microbial community and the enrichment of electroactive microorganisms. In the ATR degradation process, the swift accumulation of Hydrocarbyl ATR (HYA) was identified as the primary cause for the rapid degradation of ATR in electron-rich conditions. Essentially, HA facilitates the reduction of ATR to HYA through mediated bonded electron transfer, thereby markedly enhancing the efficiency of ATR degradation.

Evaluation value and mechanism of ADRB2 and FCER1B gene polymorphisms in preterm infants with congenital respiratory diseases.

In this study, we observed the value of ADRB2 and FCER1B gene polymorphisms in evaluating congenital respiratory diseases in preterm infants (PTIs), analyzed their effects on airway smooth muscle cells (ASMCs), and preliminarily discussed the underlying mechanism. First, we placed 64 healthy PTIs (control group) and 45 PTIs with congenital respiratory diseases (research group) born at our hospital from April 2021 to June 2023 were selected as the research subjects. Through testing, we found that the carriers of AA genotype of the polymorphic marker rs1042713 of the ADRB2 gene and that of the rs569108 locus of the FCER1B gene were less in the research group compared with the control group (P<0.05). Preterm infants carrying the GG genotype had a 2.887-fold (P<0.05) increased risk of developing congenital respiratory disease under the recessive model at the rs1042713 locus of the ADRB2 gene. Under the dominant model, preterm infants who did not carry the AA genotype had a 3.070-fold (P<0.05) increased risk of developing congenital respiratory disease. Subsequently, the constructed abnormal expression vectors of ADRB2 and FCER1B were transfected into ASMCs to examine changes in cell activity and pyroptosis. We found that up-regulating ADRB2 and FCERIB expression promoted ASMC proliferation and inflammatory reactions, inhibited apoptosis, and accelerated pyroptosis (P<0.05); silencing their expression, however, led to the opposite effect. In conclusion, the ADRB2 and FCERIB gene polymorphisms are strongly correlated with congenital respiratory diseases, which can provide a reference for clinical evaluation of congenital respiratory diseases in PTIs.

Specific Short Tandem Repeat Loci Detection in Prenatal Diagnosis of Fetal Chromosomal Diseases.

It was to investigate the value of quantitative fluorescence PCR (QF-PCR) for the selection of specific short tandem repeat (STR) in prenatal diagnosis of fetal chromosomal diseases. Amniotic fluid (AF) and villus samples were obtained from 80 pregnant women at 16-20 weeks of gestation, and venous blood samples were obtained from 60 normal individuals to extract and prepare peripheral blood chromosome, AF cell chromosome, and villus cell chromosome samples for specific STR locus detection. It showed that the area ratio of AMX peak to AMY peak in the Genescan typing map of peripheral blood DNA of normal males was close to 1:1, while the Genescan typing map of peripheral blood DNA of normal females had only AMX peak and no AMY peak. Normal heterozygous individuals had an area ratio between 1 and 1.45 for venous blood, 1.002 and 1.27 for villous samples, and 1 and 1.35 for AF samples. The karyotype of a male fetus was 46, XY, inv [9] (p11: q13), and the structure of fetal chromosome 9 was inverted (interarm), and the site of structural inversion was band 1 in the short breech 1 region and band 3 in the long arm 1 region of chromosome 9. It suggested that QF-PCR can effectively identify the normal human body and cases by selecting specific STR locus detection, which has a good application value for prenatal diagnosis of fetal chromosomal diseases.

[Genetic analysis of an infant death due to a paternally derived FOXF1 somatic-gonadal mosaic variant].

OBJECTIVE: To investigate the genetic characteristics and cause of death for an infant with alveolar capillary dysplasia and pulmonary vein misalignment (ACD/MPV). METHODS: An infant with ACD/MPV diagnosed at the Affiliated Maternity and Child Health Care Hospital of Nantong University in September 2022 was selected as the study subject. Clinical data of the infant were collected. Whole exome sequencing (WES) was carried out to detect genetic variants in the skin tissue, and Sanger sequencing was performed for verifying the candidate variants in the parents. Droplet digital PCR (ddPCR) was used to determine the mosaicism ratio of the variant in different germ layer-derived samples from the father. RESULTS: The infant had died within 2 days after birth due to hypoxemia and respiratory distress. WES revealed that she has harbored a c.433C>T nonsense variant in exon 1 of the FOXF1 gene, which was unreported previously. Sanger sequencing has verified the variant in the infant, with her mother's locus being the wild-type and a minor variant peak noted in her father. ddPCR indicated that the mosaic ratio of the c.433C>T variant in the father's sperm was 27.18%, with the mosaic ratios of the variant in tissues originating from the three germ layers ranging from 11% to 28%. CONCLUSION: The c.433C>T variant derived from the paternal germline and somatic mosaicism of the FOXF1 gene had probably predisposed to the neonatal death of this infant. ddPCR is an effective method for detecting mosaic variants.

Endotoxin tolerance induced by Porphyromonas gingivalis lipopolysaccharide alters macrophage polarization.

Endotoxin tolerance refers to a state refractory to subsequent lipopolysaccharide (LPS) stimulations following a primary LPS exposure. To study the relationship between endotoxin tolerance and macrophage polarization, endotoxin tolerance was induced by 1 µg/mL LPS from the periodontal pathogen, Porphyromonas gingivalis (P. gingivalis), in peritoneal macrophages (PMs) and bone marrow-derived macrophages (BMDMs). Repeated P. gingivalis LPS challenges increased the quantities of CD206+ PMs, while the number of CD86+CD206+ PMs was reduced compared with the non-tolerant group (p < 0.05). However, there were no changes in BMDMs (p > 0.05). Down regulations of TNF-α, IL-12, nitric oxide and MMP-2 production, and upregulated IL-10, MMP-9 levels and arginase-1 activities occurred in tolerant PMs and BMDMs (p < 0.05). P. gingivalis LPS-tolerant PMs and BMDMs also enhanced scrape-wound healing abilities of 15p-1 cells (p < 0.05). Expressions of phospho-signal transducer and activator of transcription 6 (p-STAT6) and protein tyrosine phosphatase 1B (PTP1B) were increased, while p-MEK1/2 levels were downregulated in tolerant PMs and BMDMs (p < 0.05). IL-10 production in tolerant Stat6 knockdown RAW264.7 cells was lower than tolerant control cells (p < 0.05). P. gingivalis LPS-tolerant macrophages represented an intermediate state between M1/M2 polarization, which functioned as M2-like cells, and led to limited inflammatory responses and enhanced wound healing activities. The PTP1B-MEK1/2-STAT6 signaling pathway might be involved in the polarization of tolerant macrophages.

Correlation of the detection rate of upper GI cancer with artificial intelligence score: results from a multicenter trial (with video).

BACKGROUND AND AIMS: The quality of EGD is a prerequisite for a high detection rate of upper GI lesions, especially early gastric cancer. Our previous study showed that an artificial intelligence system, named intelligent detection endoscopic assistant (IDEA), could help to monitor blind spots and provide an operation score during EGD. Here, we verified the effectiveness of IDEA to help evaluate the quality of EGD in a large-scale multicenter trial. METHODS: Patients undergoing EGD in 12 hospitals were consecutively enrolled. All hospitals were equipped with IDEA developed using deep convolutional neural networks and long short-term memory. Patients were examined by EGD, and the results were recorded by IDEA. The primary outcome was the detection rate of upper GI cancer. Secondary outcomes were part scores, total scores, and endoscopic procedure time, which were analyzed by IDEA. RESULTS: A total of 17,787 patients were recruited. The total detection rate of cancer-positive cases was 1.50%, ranging from .60% to 3.94% in each hospital. The total detection rate of early cancer-positive cases was .36%, ranging from .00% to 1.58% in each hospital. The average total score analyzed by IDEA ranged from 64.87 ± 16.87 to 83.50 ± 9.57 in each hospital. The cancer detection rate in each hospital was positively correlated with total score (r = .775, P = .003). Similarly, the early cancer detection rate was positively correlated with total score (r = .756, P = .004). CONCLUSIONS: This multicenter trial confirmed that the quality of the EGD result is positively correlated with the detection rate of cancer, which can be monitored by IDEA. (Clinical trial registration number: ChiCTR2000029001.).

Hydroa vacciniforme-like lymphoproliferative disorder: A retrospective study on clinicopathological characteristics of 32 cases.

The clinicopathological features of 32 patients (17 females and 15 males) with a median age of 8 years (range, 1.5-21 years) from Southwestern China diagnosed with hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) were reviewed. At presentation, 6 patients showed only skin lesions, while 26 patients showed both skin lesions and systemic symptoms, including fever, lymphadenopathy and hepatosplenomegaly. As the disease progressed, systemic symptoms occurred in all patients. Follow-up data of 29 patients showed that 14 patients were still alive with disease with a median follow-up time of 22 months (range 3.6-71 months), and 15 patients died within a median follow-up of 6 months (range 0-60 months).

Effect of starch-derived organic acids on the removal of polycyclic aromatic hydrocarbons in an aquaculture-sediment microbial fuel cell.

This study constructed sediment microbial fuel cells (SMFCs) for polycyclic aromatic hydrocarbons (PAHs) removal in contaminated aquaculture sediment. Starch, a waste deposited in aquaculture sediment, was employed as the co-substrate for electricity generation and PAHs removal, and the effect of starch-derived organic acids on SMFC performance was assessed. The results indicated that sufficient starch promoted PAHs removal (69.9% for naphthalene, 55.6% for acenaphthene, and 46.8% for pyrene) in dual-chamber SMFC, whereas excessive starch attenuated SMFC performance because the organic acids accumulation reduced anode pH, decreased species diversity, and changed the microbial communities. The electricity generation and PAHs removal were positively correlated (R > 0.96), and both of them were related to Macellibacteroides belonging to Bacteroidetes. However, a larger single-chamber SMFC device did not obtain enhanced PAHs removal owing to the restricted "effective range" of the anode. Hence, more challenges need to be addressed to realize the practical application of SMFC.

Application of microbial fuel cell technology to the remediation of compound heavy metal contamination in soil.

Exploring the removal rules of MFC on composite heavy metal pollution is very important for the future development and field application of MFC. We constructed a three-chamber soil MFC and the results showed that with the gradual deterioration of soil heavy metal contamination from single heavy metal to metals in different oxidation states (e.g., copper (II), lead (II), and chromium (III) compounds), the internal resistance of the soil MFC increased by 2.16-2.71 times, which significantly inhibited the power production performance of the MFC. After 59 days of remediation, the migration removal efficiencies of total Cu, total Cr and total Pb from the soil under composite conditions were 36.69%, 52.35% and 19.67%, respectively. The main removal mechanisms included both electromigration and diffusion, where electromigration contributed 74.41%, 31.48% and 97.67% to the removal of total Cu, Cr and Pb, respectively. The removal of composite heavy metals was affected by adsorption-desorption competition and synergism. The competition of Pb for specific adsorption sites in soil leads to the increase of mobility of Cr and Cu, which is conducive to migration and removal. The migration of Cu and Pb ions to the cathode inhibited the diffusion of Cr to the anode; however, it drove the synergistic migration of Pb ions to the cathode. For the heavy metals migrated from the soil into the catholyte, only Cu2+ with high redox potential is reduced to copper at the cathode.

A nationwide post-marketing survey of knowledge, attitudes and recommendations towards human papillomavirus vaccines among healthcare providers in China.

Since licensure of human papillomavirus (HPV) vaccine in mainland China, little research has been conducted about healthcare providers' (HCPs) understanding and recommendation of HPV vaccine. A multi-stage convenience sample of Chinese HCPs (N = 5270) were surveyed, involving obstetrician-gynecologists, HCPs from Division of Expanded Program on Immunization (DEPI), Community Health Center (CHC) and other non-HPV closely related professions. Binary logistic regression was conducted to explore factors associated with knowledge and recommendation behaviors. Overall, HCPs showed basic HPV/HPV vaccine knowledge with median (interquartile range) score at 9.5 (7.5-11.6) out of 16 and relatively high recommendation behavior (74.8%). Identified knowledge gaps among HCPs included risk factors of HPV infection, best time to vaccinate, prophylactic functions of HPV vaccine and especially classification of low-risk and high-risk types. Profession-specific analysis in individual knowledge item showed HCPs from CHC were suboptimal on HPV while obstetrician-gynecologists were less competent on HPV vaccine knowledge. Obstetrician-gynecologists also recommended vaccination less frequently than HCPs from DEPI and CHC. Besides being key predictors of recommendation practice (2.74, 95% CI: 2.34-3.21), knowledge shared independent determinants with recommendation behavior on age and ethnicity and additionally associated with education and title by itself. Findings highlight overall and profession-specific gaps on HPV and HPV vaccine knowledge and recommendation practice. Future education and training efforts should be profession-niche-targeting and focus much on HCPs with lower title or education background and from minorities.

Effects of cathode/anode electron accumulation on soil microbial fuel cell power generation and heavy metal removal.

Microbial fuel cells (MFCs) with different electrode configurations were constructed to study the mechanism of influence of multiple current paths on their electrical performance and the removal of heavy metals in soil. Three types of MFCs were constructed, namely, double anode-single cathode (DASC), single anode-dual cathode (SADC), and single anode-single cathode (SASC). The total electricity generation of the three kinds of MFC was similar: 143.44 × 10-3 mW, 114.90 × 10-3 mW, and 132.50 × 10-3 mW, respectively. However, the maximum voltage and cathode current density produced by a single current path differed significantly. The corresponding values were 0.27, 0.23, and 0.42 V and 0.130, 0.122, and 0.096 A/m 2, respectively. The SASC had the best electricity generation performance. Based on a limited reduction rate of oxygen at the cathode, the accumulation of cathode electrons was facilitated by the construction of multiple current paths in the MFC, which significantly increased the cathode electron transfer resistance and limited the electricity generation performance of the MFC. However, at the same time, the construction of multiple current paths promoted output of more electrons in the anode, reducing the retention of anode electrons and anode electron transfer resistance. The heavy metal removal efficiencies of SASC, DASC, and SADC were 2.68, 2.18, and 1.70 times that of the open circuit group, respectively. The migration of heavy metals in the soil depended mainly on the internal electric field intensity of the MFC rather than the total electricity generation. As the internal electric field intensity increased, the removal efficiency of heavy metals in the MFC increased.

Overcoming chemotherapy resistance using pH-sensitive hollow MnO2 nanoshells that target the hypoxic tumor microenvironment of metastasized oral squamous cell carcinoma.

BACKGROUND: Smart nanoscale drug delivery systems that target acidic tumor microenvironments (TME) could offer controlled release of drugs and modulate the hypoxic TME to enhance cancer therapy. The majority of previously reported MnO2 nanostructures are nanoparticles, nanosheets, or nanocomposites incorporated with other types of nanoparticles, which may not offer the most effective method for drug loading or for the controlled release of therapeutic payloads. Previous studies have designed MnO2 nanoshells that achieve tumor-specific and enhanced combination therapy for localized advanced cancer. However, the therapeutic effect of MnO2 nanoshells on metastatic cancer is still uncertain. RESULT: Here, intelligent "theranostic" platforms were synthesized based on hollow mesoporous MnO2 (H-MnO2) nanoshells that were loaded with chemotherapy agents docetaxel and cisplatin (TP) to form H-MnO2-PEG/TP nanoshells, which were designed to alleviate tumor hypoxia, attenuate angiogenesis, trigger the dissolution of Mn2+, and synergize the efficacy of first-class anticancer chemotherapy. The obtained H-MnO2-PEG/TP nanoshells decomposed in the acidic TME, releasing the loaded drugs (TP) and simultaneously attenuated tumor hypoxia and hypoxia-inducible factor-1α (HIF-1α) expression by inducing endogenous tumor hydrogen peroxide (H2O2) decomposition. In vitro experiments showed that compared with the control group, the proliferation, colony formation and migration ability of CAL27 and SCC7 cells were significantly reduced in H-MnO2-PEG/TP group, while cell apoptosis was enhanced, and the expression of hypoxia-inducible factor-1α(HIF-1α) was down-regulated. In vivo experiments showed that tumor to normal organ uptake ratio (T/N ratio) of mice in H-MnO2-PEG/TP group was significantly higher than that in TP group alone (without the nanoparticle), and tumor growth was partially delayed. In the H-MnO2-PEG/TP treatment group, HE staining showed that most of the tumor cells were severely damaged, and TUNEL assay showed cell apoptosis was up-regulated. He staining of renal and liver sections showed no obvious fibrosis, necrosis or hypertrophy, indicating good biosafety. Fluorescence staining showed that HIF-1α expression was decreased, suggesting that the accumulation of MnO2 in the tumor caused the decomposition of H2O2 into O2 and alleviated the hypoxia of the tumor. CONCLUSION: In conclusion, a remarkable in vivo and in vitro synergistic therapeutic effect is achieved through the combination of TP chemotherapy, which simultaneously triggered a series of antiangiogenic and oxidative antitumor reactions.

Simultaneous enhancement of heavy metal removal and electricity generation in soil microbial fuel cell.

As an environmentally sustainable bioelectrochemical technology, the microbial fuel cell (MFC) has attracted great attention. In this study, a three-chamber MFC (TC-MFC) was enhanced with different auxiliary reagents to remove heavy metals from soil. The results showed that the removal efficiency of heavy metals from soil increased with increasing auxiliary reagent concentration. When 1 mol/L citric acid, HCl, or acetic acid were used as an auxiliary reagent, the total copper (500 mg/kg) removal efficiency after 74 days of TC-MFC treatment was 3.89, 5.01 and 2.01 times that of the control group, respectively. The highest soil electrical conductivity (15.29 ms/cm), ionic heavy metal content (94.78%), electricity generation performance (363.04 mW h), and desorption stability of heavy metals were obtained when using 1 mol/L HCl as an auxiliary reagent, indicating that HCl was more suitable for the remediation of heavy metals in soil using a TC-MFC. Correlation analysis showed that the electricity generation of the TC-MFC was linearly related to the removal efficiency of heavy metals from soil (R2 = 0.9296). At the same time, higher content of ionic heavy metals in the soil led to better migration of heavy metals under the internal electric field of the TC-MFC.

Correlation between the Glasgow-Blatchford score, shock index, and Forrest classification in patients with peptic ulcer bleeding

Background/aim: To investigate the correlation between the Glasgow-Blatchford score, shock index, and Forrest classification in patients with peptic ulcer bleeding (PUB). Materials and methods: A total of 955 patients with PUB were assessed using the Glasgow-Blatchford score and shock index, as well as the Forrest classification based on their gastroscopy results. The correlation between the Glasgow-Blatchford score and shock index was determined using scatter plot analysis, and the correlation between the Glasgow-Blatchford score or shock index and Forrest classification was determined using Spearman's analysis. Results: Both the Glasgow-Blatchford score and shock index showed the highest values in patients with Forrest class IIa. The Glasgow- Blatchford score was significantly higher than patients with Forrest class Ib/IIc/III (P < 0.05), and the shock index was significantly higher than patients with Forrest class Ib/IIb/III (P < 0.05). A positive correlation was observed between the Glasgow-Blatchford score and shock index, at r = 0.427 (P < 0.001). A negative correlation was observed between the Glasgow-Blatchford score and Forrest classification, at r = ­0.111 (P < 0.01), and between the shock index and Forrest classification, at r = ­0.138 (P < 0.01). Conclusion: A moderate correlation was observed between the Glasgow-Blatchford score and shock index in patients with PUB, and the correlation between the Forrest classification and Glasgow-Blatchford score or shock index was relatively low.

Whole genome assembly and functional portrait of hypervirulent extensively drug-resistant NDM-1 and KPC-2 co-producing Klebsiella pneumoniae of capsular serotype K2 and ST86.

OBJECTIVES: To characterize an emergent carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) strain, NUHL30457, which co-produces NDM-1 and KPC-2 carbapenemases. METHODS: We performed WGS analysis on a clinical carbapenemase-producing hypervirulent K. pneumoniae (CP-hvKP) strain NUHL30457. Sequence data were analysed using comparative genomics and phylogenetics. WGS was used to perform MLST, capsular genotyping and identification of virulence and antimicrobial resistance genes. The virulence of NUHL30457 was analysed by serum killing assay, neutrophil phagocytosis and mouse lethality assay. RESULTS: The NUHL30457 strain was carbapenem resistant and belonged to ST86 and serotype K2. A significant increase in resistance to serum killing and antiphagocytosis was found in the NUHL30457 strain compared with the reference strain. The murine lethality assay showed an LD50 of 2.5 × 102 cfu for the NUHL30457 strain, indicating hypervirulence. WGS revealed that NUHL30457 has a single 5.3 Mb chromosome (57.53% G + C content) and four plasmids in the range 49.2-215.7 kb. The incompatibility group (Inc)N plasmid p30457-4 carried the blaNDM-1 and qnrS1 genes. The IncFII(K) plasmid p30457-3 also carried an array of resistance elements, including blaCTX-M-65, blaTEM-1 and blaKPC-2. The IncHI1/IncFIB plasmid p30457-1, which carried virulence genes, was identical to a pLVPK plasmid reported previously. CONCLUSIONS: To the best of our knowledge, this is the first report to isolate an ST86 hvKP strain that co-produces NDM-1 and KPC-2 carbapenemase. Further investigation is required to reinforce our understanding of the epidemiology and virulence mechanisms of this clinically significant CP-hvKP.

Analysis of cardiovascular risk factors associated with serum testosterone levels according to the US 2011-2012 National Health and Nutrition Examination Survey.

OBJECTIVE: To investigate associations between cardiovascular disease risk factors, including fasting glucose, cholesterol, high density lipoprotein cholesterol (HDL-c), LDL-c, blood pressure, body mass index (BMI), C-peptide, creatinine kinase, smoking, alcohol use, physical activity, C-reactive protein as well as homocysteine levels and cardiovascular events. METHODS: Data from 1545 men aged ≥40 years, with testosterone deficiency (TD) (<300 ng/dL) and non-TD (≥300 ng/dL) which were extracted from the National Health and Nutrition Examination Survey database 2011-2012 and analyzed. RESULTS: Multivariate logistic regression analysis showed positive associations between TD and BMI (≥35 vs. < 18.5: OR = 2.51, 95% CI: 1.19-5.32, p = .016), HDL-c (<0.91 vs. ≥0.91: OR = 1.60, 95% CI: 1.14-2.24, p = .006) and diabetes (diabetes vs. non-diabetes: OR = 1.48, 95% CI: 1.14-1.92, p = .004) as well as negative associations between TD and metabolic equivalent scores (≥12 vs. <12: OR = 0.69, 95% CI: 0.52-0.91, p = .009) and smoking (Ever vs. never: OR = 0.69, 95% CI: 0.51-0.94, p = .018). Furthermore, total serum testosterone levels were lower in patients with heart failure (p = .04) and angina/angina pectoris (p = .001) compared with subjects without these cardiac problems. CONCLUSION: Low serum testosterone was associated with multiple risk factors for CHD.

Regioselective C-C cross-coupling of 1,2,4-thiadiazoles with maleimides through iridium-catalyzed C-H activation.

A regioselective C-C cross-coupling of 1,2,4-thiadiazoles with maleimides through iridium catalysis was developed. This transformation tactically linked the 1,2,4-thiadiazoles and succinimides together, and the novel molecules formed may have potential biological activity.

C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis.

The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. C11 was a selective FGFR1 inhibitor with an IC50 of 19 nM among a panel of 20 tyrosine kinases. C11 inhibited cell proliferation in various tumors, particularly bladder cancer and breast cancer. C11 also inhibited breast cancer MDA-MB-231 cell migration and invasion via suppression of FGFR1 phosphorylation and its downstream signaling pathway. Suppression of matrix metalloproteinases 2/9 (MMP2/9) was associated with the anti-motility activity of C11. Furthermore, the anti-angiogenesis activity of C11 was verified in endothelial cells and chicken chorioallantoic membranes (CAMs). C11 inhibited the migration and tube formation of HMEC-1 endothelial cells and inhibited angiogenesis in a CAM assay. In sum, C11 is a novel selective FGFR1 inhibitor that exhibits potent activity against breast cancer metastasis and angiogenesis.