[Evaluation of efficacy of Dihuang Baoyuan Granules for diabetes mellitus and composition and in vivo distribution analysis based on UHPLC-LTQ-Orbitrap MS].

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.

Diagnostic accuracy of a liquid chromatography-tandem mass spectrometry assay in small hair samples for rifampin-resistant tuberculosis drug concentrations in a routine care setting.

BACKGROUND: Treatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure. METHODS: Small hair samples were collected from participants at various timepoints during directly observed RR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed qualitative determination (i.e., detection above limit of detection) of bedaquiline, linezolid, clofazimine, pretomanid, levofloxacin, moxifloxacin, pyrazinamide, isoniazid, ethambutol, ethionamide, and prothionamide in an LC-MS/MS index panel assay against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization were not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid (HIV/LTBI cohort) in Uganda. RESULTS: Among the 57 DR-TB patients (58% with pre-XDR/XDR-TB; 70% HIV-positive) contributing analyzable hair samples, the sensitivity of the investigational assay was 94% or higher for all drugs except ethionamide (58.5, 95% confidence interval [CI], 40.7-99.9). Assay specificity was low across all tested analytes within the DR-TB cohort; conversely, assay specificity was 100% for all drugs in the HIV/LTBI cohort. CONCLUSIONS: Hair drug concentrations reflect long-term exposure, and multiple successive regimens commonly employed in DR-TB treatment may result in apparent false-positive qualitative and falsely elevated quantitative hair drug levels when prior treatment histories within the hair growth window are not known.

Comparisons of microbiological characteristics and antibiotic resistance of Klebsiella pneumoniae isolates from urban rodents, shrews, and healthy people.

BACKGROUND: The comparisons of molecular characterization and antibiotic resistance of Klebsiella pneumoniae (KP) isolates from humans and other animal hosts are not well studied. Our goal was to compare the molecular epidemiology of KP strains that were isolated from urban rodents, shrews, and healthy people. RESULTS: K. pneumoniae (KP) isolates were isolated from fecal samples of rodents, shrews and healthy adults in 2015 in southern China. In total, 465 fecal samples were collected, of which 85 from rodents, 105 from shrews, and 275 from healthy adults. Antimicrobial susceptibility and production of extended-spectrum ß-lactamases (ESBL) of the isolates were tested. PCR-based methods were used to detect specific genes, including ESBL genes (blaTEM, blaSHV, and blaCTX-M) in ESBL-producing isolates, capsular serotypes (K1, K2, K5, K20, K54, and K57) in hypervirulent KPs (hvKPs), and virulence genes (magA, wcaG, rmpA, uge, kfu, and aerobactin) in hvKP isolates. Multilocus sequence type (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to exclude the homology of these isolates. The carriage rate of KP in urban rodents and shrews (78.42%) was higher than that in healthy adults (66.18%) (χ2 = 8.206, P = 0.004). The prevalence rates of ESBL-producing isolates among rodents, shrews, and humans were 7.94, 12.79, and 17.03%, respectively. The positive rates of CTX-M, TEM and SHV types in ESBL-producing isolates were 29.79, 27.66, and 17.02%, respectively. Serotype K1, K5, K20, and K57 were detected in both small mammals and humans. PFGE typing revealed thirty-six clusters. PFGE cluster A was clustered by samples of shrews and healthy adult, with a similarity of 88.4%. MLST typing revealed thirty-eight types. ST23 and ST35 were detected in samples of shrews and healthy adults. ST37 was detected in samples of 2 rodents and a healthy adult. CONCLUSIONS: Overlapping serotypes of hvKP were observed in both the animals and humans. The same PFGE or MLST types were also found in isolates derived humans, rodents and shrews. Therefore, urban rodents and shrews might play a certain role in the transmission of drug-resistant and hypervirulent KP.

Composition of gut and oropharynx bacterial communities in Rattus norvegicus and Suncus murinus in China.

BACKGROUND: Rattus norvegicus and Suncus murinus are important reservoirs of zoonotic bacterial diseases. An understanding of the composition of gut and oropharynx bacteria in these animals is important for monitoring and preventing such diseases. We therefore examined gut and oropharynx bacterial composition in these animals in China. RESULTS: Proteobacteria, Firmicutes and Bacteroidetes were the most abundant phyla in faecal and throat swab samples of both animals. However, the composition of the bacterial community differed significantly between sample types and animal species. Firmicutes exhibited the highest relative abundance in throat swab samples of R. norvegicus, followed by Proteobacteria and Bacteroidetes. In throat swab specimens of S. murinus, Proteobacteria was the predominant phylum, followed by Firmicutes and Bacteroidetes. Firmicutes showed the highest relative abundance in faecal specimens of R. norvegicus, followed by Bacteroidetes and Proteobacteria. Firmicutes and Proteobacteria had almost equal abundance in faecal specimens of S. murinus, with Bacteroidetes accounting for only 3.07%. The family Streptococcaceae was most common in throat swab samples of R. norvegicus, while Prevotellaceae was most common in its faecal samples. Pseudomonadaceae was the predominant family in throat swab samples of S. murinus, while Enterobacteriaceae was most common in faecal samples. We annotated 33.28% sequences from faecal samples of S. murinus as potential human pathogenic bacteria, approximately 3.06-fold those in R. norvegicus. Potential pathogenic bacteria annotated in throat swab samples of S. murinus were 1.35-fold those in R. norvegicus. CONCLUSIONS: Bacterial composition of throat swabs and faecal samples from R. norvegicus differed from those of S. murinus. Both species carried various pathogenic bacteria, therefore both should be closely monitored in the future, especially for S. murinus.

Methicillin-resistant Staphylococcus aureus among urban rodents, house shrews, and patients in Guangzhou, Southern China.

BACKGROUND: The transmission of methicillin-resistant Staphylococcus aureus (MRSA) between humans and animals has been identified in a number of countries. In this study, MRSA in urban rodents and shrews in a community was investigated. Further, comparisons of MRSA isolates from rodents, shrews, and humans were conducted to evaluate the relationships of these isolates from different origins. RESULTS: Between 2015 and 2016, 397 oropharynx samples from 212 rodents and 185 shrews, and 8 MRSA isolates from hospital patients were collected. Twelve MRSA were isolated from the small mammals (3.0, 95%CI: 1.3-4.7%), including 11 isolates from rodents and one from a shrew. Three MRSA isolates from Rattus norvegicus were PVL-positive, and seven isolates were IEC-negative (one from Suncus murinus, five from Rattus norvegicus, and one from a patient). The spa type, MLST, and antimicrobial resistance patterns showed that the MRSA retrieved from rodents and shrews are likely related to human strains. CONCLUSION: MRSA derived from rodent shares similar antimicrobial resistance and molecular characteristics to those from humans, suggesting that urban rodents may play as maintenance host or vectors for MRSA which is important to human health.

Viral metagenomics of six bat species in close contact with humans in southern China.

Accumulating studies have shown that bats could harbor various important pathogenic viruses that could be transmitted to humans and other animals. Extensive metagenomic studies of different organs/tissues from bats have revealed a large number of novel or divergent viruses. To elucidate viral diversity and epidemiological and phylogenetic characteristics, six pooled fecal samples from bats were generated (based on bat species and geographic regions characteristic for virome analysis). These contained 500 fecal samples from six bat species, collected in four geographic regions. Metagenomic analysis revealed a plethora of divergent viruses originally found in bats. Multiple contigs from influenza A virus and coronaviruses in bats shared high identity with those from humans, suggesting possible cross-species transmission, whereas a number of contigs, whose sequences were taxonomically classifiable within Alphapapillomavirus, Betaretrovirus, Alpharetrovirus, Varicellovirus, Cyprinivirus, Chlorovirus and Cucumovirus had low identity to viruses in existing databases, which indicated possible evolution of novel viral species. None of the established caliciviruses and picornaviruses were found in the 500 fecal specimens. Papillomaviruses with high amino acid identity were found in Scotophilus kuhlii and Rhinolophus blythi, challenging the hypotheses regarding the strict host specificity and co-evolution of papillomaviruses. Phylogenetic analysis showed that four bat rotavirus A strains might be tentative G3 strains, according to the Rotavirus Classification Working Group classification.

The Risk of Human Papillomavirus Infection for Spontaneous Abortion, Spontaneous Preterm Birth, and Pregnancy Rate of Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis.

AIMS: To estimate the impact of human papillomavirus (HPV) infection on spontaneous abortion, spontaneous preterm birth (sPTB), pregnancy rate of females undergoing assisted reproductive technologies (ART), and spontaneous abortion of ART pregnancy. METHODS: PubMed, Medline, Embase, and the Cochrane Library were searched until December 16, 2016. The OR or relative risk (RR) with its corresponding 95% CI were selected as effect size. Subgroup analysis of HPV genotype infection (high-risk HPV [HR-HPV] or indiscriminate genotype) was performed. Statistical analysis was conducted using STATA 12.0. RESULTS: Eighteen studies were included. Eight studies revealed no significant association between HPV infection and spontaneous abortion (OR 1.40, 95% CI 0.56-3.50). However, subgroup analysis showed indiscriminate genotype HPV infection increased the ratio of spontaneous abortion with OR of 2.24 (95% CI 1.37-3.65), while HR-HPV infection had no significant effect (OR 0.65, 95% CI 0.21-1.98). The results indicated that HR-HPV infection was a risk for sPTB with a pooled OR of 2.84 (95% CI 1.95-4.14). HPV infection was found to be independent of the ART-based clinical pregnancy rate (RR 1.04, 95% CI 0.64-1.70) and spontaneous abortion of ART pregnancy (RR 1.47, 95% CI 0.86-2.50). CONCLUSIONS: Indiscriminate HPV genotype infection can increase the risk of spontaneous abortion and HR-HPV infection was a risk factor for sPTB. However, there was not enough evidence to indicate the association between HPV infection and pregnancy rate of ART, and spontaneous abortion of ART pregnancy. Different genotypes of HPV infection may play a discrepant role in adverse pregnancy outcomes.

Development and Validation of a Quantitative, One-Step, Multiplex, Real-Time Reverse Transcriptase PCR Assay for Detection of Dengue and Chikungunya Viruses.

Dengue virus (DENV) and chikungunya virus (CHIKV) are important human pathogens with common transmission vectors and similar clinical presentations. Patient care may be impacted by the misdiagnosis of DENV and CHIKV in areas where both viruses cocirculate. In this study, we have developed and validated a one-step multiplex reverse transcriptase PCR (RT-PCR) to simultaneously detect, quantify, and differentiate between four DENV serotypes (pan-DENV) and chikungunya virus. The assay uses TaqMan technology, employing two forward primers, three reverse primers, and four fluorophore-labeled probes in a single-reaction format. Coextracted and coamplified RNA was used as an internal control (IC), and in vitro-transcribed DENV and CHIKV RNAs were used to generate standard curves for absolute quantification. The diagnostic 95% limits of detection (LOD) within the linear range were 50 and 60 RNA copies/reaction for DENV (serotypes 1 to 4) and CHIKV, respectively. Our assay was able to detect 53 different strains of DENV, representing four serotypes, and six strains of CHIKV. No cross-reactivity was observed with related flaviviruses and alphaviruses, To evaluate diagnostic sensitivity and specificity, 89 clinical samples positive or negative for DENV (serotypes 1 to 4) and CHIKV by the standard virus isolation method were tested in our assay. The multiplex RT-PCR assay showed 95% sensitivity and 100% specificity for DENV and 100% sensitivity and specificity for CHIKV. With an assay turnaround time of less than 2 h, including extraction of RNA, the multiplex quantitative RT-PCR assay provides rapid diagnosis for the differential detection of two clinically indistinguishable diseases, whose geographical occurrence is increasingly overlapping.

High prevalence and diversity of viruses of the subfamily Gammaherpesvirinae, family Herpesviridae, in fecal specimens from bats of different species in southern China.

Several studies have reported the detection of herpesviruses (HVs) in bats. However, the prevalence and phylogenetic characteristics of HVs in bats are still poorly understood. To elucidate the epidemiological characteristics of bat HVs in southern China, 520 fecal samples from eight bat species were collected in four geographic regions of southern China. Of these samples, 73 (14.0 %) tested positive for HVs using nested polymerase chain reaction assay. Phylogenetic analysis revealed a high degree of molecular diversity of HVs in bats of different species from different geographic regions. Our study provides evidence for co-evolution of bats and HVs.

Detection of novel adenoviruses in fecal specimens from rodents and shrews in southern China.

The prevalence and phylogenetic characteristics of AdVs in rodents and shrews in China are still unknown. To explore the epidemiological characteristics of rodent and shrew AdVs in southern China, 255 fecal samples derived from four rodent species and 90 from shrews were collected in Xiamen and Guangzhou city of southern China. Amplification of a 314-324-bp fragment from the DNA polymerase gene of AdVs was attempted by using a nested PCR. Twenty-nine (11.4 %) specimens from rodents and one (1.1 %) specimen from shrews were tested positive for AdVs. Phylogenetic analysis revealed that nine samples from Rattus norvegicus in Guangzhou city between 2012 and 2013 might be the genuine AdV of R. norvegicus. The same putative AdV sequences were derived from samples of different host species from different/same places. A novel adenovirus was detected in Suncus murinus Linnaeus (SML/14GDGZ72) for the first time. Our findings provide new data on the prevalence and diversity of AdVs in rodents and shrews.

Pupillary capture following sutureless scleral-fixated intraocular lens in children with Marfan syndrome.

AIM: To compare the clinical outcomes between two approaches for sutureless scleral-fixated intraocular lens (SFIOL) in children with Marfan syndrome (MFS). METHODS: The study included 15 children (26 eyes) with lens subluxation due to MFS. These children underwent lensectomy, anterior vitrectomy, and sutureless SFIOL. According to the position of placement of intraocular lens (IOL) haptics, two study groups were reviewed for best corrected visual acuity (BCVA) and postoperative complications: group A, 14 eyes with haptics fixated at 2.0 mm from the limbus; group B, 12 eyes with the haptics fixated at 2.5 mm from the limbus. RESULTS: The mean axial length for all patients was 25.66±2.35 mm. Postoperative BCVA in logMAR were significant improved in both groups (0.77±0.32 to 0.17±0.12 in group A, 0.66±0.25 to 0.24±0.12 in group B, both P<0.001) while no significant difference between two groups (P>0.05). Pupillary capture was main postoperative complication, occurring between 3d and 18mo. It occurred in 7 eyes in group A and one eye in group B (P=0.02). CONCLUSION: Sutureless SFIOL is an effective treatment approach for lens subluxation in children with MFS. Pupillary capture is the main postoperative complication. Fixated IOL haptics at 2.5 mm from the limbus can reduce the occurrence of pupillary capture.

Facile magnetization of metal-organic framework MIL-101 for magnetic solid-phase extraction of polycyclic aromatic hydrocarbons in environmental water samples.

The unusual properties such as high surface area, good thermal stability, uniform structured nanoscale cavities and the availability of in-pore functionality and outer-surface modification make metal-organic frameworks (MOFs) attractive for diverse analytical applications. However, integration of MOFs with magnets for magnetic solid-phase extraction for analytical application has not been attempted so far. Here we show a facile magnetization of MOF MIL-101(Cr) for rapid magnetic solid-phase extraction of polycyclic aromatic hydrocarbons (PAHs) from environmental water samples. MIL-101 is attractive as a sorbent for solid-phase extraction of pollutants in aqueous solution due to its high surface area, large pores, accessible coordinative unsaturated sites, and excellent chemical and solvent stability. In situ magnetization of MIL-101 microcrystals as well as magnetic solid-phase extraction of PAHs was achieved simultaneously by simply mixing MIL-101 and silica-coated Fe(3)O(4) microparticles in a sample solution under sonication. Such MOF-based magnetic solid-phase extraction in combination with high-performance liquid chromatography gave the detection limits of 2.8-27.2 ng L(-1) and quantitation limits of 6.3-87.7 ng L(-1) for the PAHs. The relative standard deviations for intra- and inter-day analyses were in the range of 3.1-8.7% and 6.1-8.5%, respectively. The results showed that hydrophobic and π-π interactions between the PAHs and the framework terephthalic acid molecules, and the π-complexation between PAHs and the Lewis acid sites in the pores of MIL-101 play a significant role in the adsorption of PAHs.

Development and evaluation of a predictive nomogram for survival in heat stroke patients: a retrospective cohort study.

BACKGROUND: This study aimed to establish an effective nomogram to predict the survival of heat stroke (HS) based on risk factors. METHODS: This was a retrospective, observational multicenter cohort study. We analyzed patients diagnosed with HS, who were treated between May 1 and September 30, 2018 at 15 tertiary hospitals from 11 cities in Northern China. RESULTS: Among the 175 patients, 32 patients (18.29%) died before hospital discharge. After the univariate analysis, mechanical ventilation, initial mean arterial pressure <70 mmHg, maximum heart rate, lab results on day 1 (white blood cell count, alanine aminotransferase, creatinine), and Glasgow admission prediction score were included in multivariate analysis. Multivariate Cox regression showed that invasive ventilation, initial mean arterial pressure <70 mmHg (1 mmHg=0.133 kPa), and Glasgow admission prediction score were independent risk factors for HS. The nomogram was established for predicting 7-d and 14-d survival in the training cohort. The nomogram exhibited a concordance index (C-index) of 0.880 (95% confidence interval [95% CI] 0.831-0.930) by bootstrapping validation (B=1,000). Furthermore, the nomogram performed better when predicting 14-d survival, compared to 7-d survival. The prognostic index cut-off value was set at 2.085, according to the operating characteristic curve for overall survival prediction. The model showed good calibration ability in the internal and external validation datasets. CONCLUSION: A novel nomogram, integrated with prognostic factors, was proposed; it was highly predictive of the survival in HS patients.

catena-Poly[[[triaqua-europium(III)]-µ-(1H-benzimidazole-5,6-dicarboxyl-ato-κO:O)-µ-(1H,3H-benzimidazol-3-ium-5,6-dicarboxyl-ato-κO:O,O)] dihydrate].

In the title one-dimensional coordination polymer, {[Eu(C(9)H(4)N(2)O(4))(C(9)H(5)N(2)O(4))(H(2)O)(3)]·2H(2)O}(n), one of the 1H-benzimidazole-5,6-dicarboxyl-ate (Hbdc) ligands is protonated at the imidazole group (H(2)bdc). The Eu(III) ion is eight-coordinated by two O atoms from two Hbdc ligands, three O atoms from two H(2)bdc ligands and three water mol-ecules, showing a distorted square-anti-prismatic geometry. The Eu(III) ions are bridged by the carboxyl-ate groups of the Hbdc and H(2)bdc ligands, forming a chain along [110], with an Eu⋯Eu separation of 5.4594 (3) Å. These chains are further connected by inter-molecular O-H⋯O, N-H⋯O and N-H⋯N hydrogen bonds, as well as π-π inter-actions between the imidazole and benzene rings [centroid-centroid distances = 3.558 (3), 3.906 (2), 3.397 (3), 3.796 (2) and 3.898 (2) Å], into a three-dimensional supra-molecular network.

Poly[µ-aqua-diaqua(µ(3)-1H-benzimid-azole-5-carboxylato-κN:O,O')(µ(2)-1H-benzimidazole-5-carboxylato-κN:O:O')-µ(5)-sulfato-µ(4)-sulfato-tri-cadmium].

The asymmetric unit of the title compound, [Cd(3)(C(8)H(5)N(2)O(2))(2)(SO(4))(2)(H(2)O)(3)](n), contains three Cd(II) ions, two sulfate anions, two 1H-benzimidazole-5-carboxyl-ate (H(2)bic) ligands and three coordinated water mol-ecules. One Cd(II) ion is six-coordinated and exhibits a distorted octa-hedral geometry, while the other two Cd(II) ions are seven-coordinated, displaying a distorted penta-gonal-bipyramidal geometry. The Cd(II) ions are bridged by two types of sulfate anions, producing inorganic chains along [100]. These chains are further connected by the H(2)bic ligands, leading to a three-dimensional framework. N-H⋯O and O-H⋯O hydrogen bonds and π-π inter-actions between the imidazole and benzene rings [centroid-centroid distances = 3.953 (2), 3.507 (2), 3.407 (2) and 3.561 (2) Å] further stabilize the crystal structure.

Outbreak of febrile respiratory illness associated with adenovirus 11a infection in a Singapore military training cAMP.

Outbreak cases of acute respiratory disease (ARD) associated with subspecies B2 human adenovirus 11a (HAdV-11a) infection were detected during 2005 in a military basic training camp in Singapore. The Singapore HAdV-11a strain is highly similar to other Asian strains of HAdV-11, including strain QS-DLL, which is responsible for the recently described 2006 outbreak of ARD in China.

Genome sequences of human adenovirus 14 isolates from mild respiratory cases and a fatal pneumonia, isolated during 2006-2007 epidemics in North America.

BACKGROUND: Human adenovirus 14 (HAdV-14) is a recognized causative agent of epidemic febrile respiratory illness (FRI). Last reported in Eurasia in 1963, this virus has since been conspicuously absent in broad surveys, and was never isolated in North America despite inclusion of specific tests for this serotype in surveillance methods. In 2006 and 2007, this virus suddenly emerged in North America, causing high attack rate epidemics of FRI and, in some cases, severe pneumonias and occasional fatalities. Some outbreaks have been relatively mild, with low rates of progression beyond uncomplicated FRI, while other outbreaks have involved high rates of more serious outcomes. METHODOLOGY AND FINDINGS: In this paper we present the complete genomic sequence of this emerging pathogen, and compare genomic sequences of isolates from both mild and severe outbreaks. We also compare the genome sequences of the recent isolates with those of the prototype HAdV-14 that circulated in Eurasia 30 years ago and the closely related sequence of HAdV-11a, which has been circulating in southeast Asia. CONCLUSIONS: The data suggest that the currently circulating strain of HAdV-14 is closely related to the historically recognized prototype throughout its genome, though it does display a couple of potentially functional mutations in the fiber knob and E1A genes. There are no polymorphisms that suggest an obvious explanation for the divergence in severity between outbreak events, suggesting that differences in outcome are more likely environmental or host determined rather than viral genetics.

catena-Poly[silver(I)-µ-acridine-9-carboxyl-ato-κN:O,O'].

In the title coordination polymer, [Ag(C(14)H(8)NO(2))](n), the Ag(I) cation is coordinated by two O atoms and one N atom from two symmetry-related acridine-9-carboxyl-ate ligands in a distorted trigonal-planar geometry. The metal atoms are connected by the ligands to form chains running parallel to the b axis. π-π stacking inter-actions [centroid-to-centroid distances 3.757 (2)-3.820 (2) Å] and weak Ag⋯O inter-actions further link the chains to form a layer network parallel to the ab plane. The Ag(I) cation is disordered over two positions, with refined site-occupancy factors of 0.73 (3):0.27 (3).

STEAP1 facilitates metastasis and epithelial-mesenchymal transition of lung adenocarcinoma via the JAK2/STAT3 signaling pathway.

Six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a relatively newly identified gene target from prostate cancer, breast cancer, and gastric cancer. However, functions of STEAP1 in lung adenocarcinoma (LUAD) are still unknown. In the present study, we explored the molecular and cellular mechanisms of STEAP1 in LUAD. Western blot and Q-PCR were conducted to detect the protein and mRNA expressions respectively. The cell proliferation was tested by CCK8 assay. The effects of STEAP1 on the metastasis and epithelial-mesenchymal transition (EMT) of LUAD were evaluated by EdU assay, wound healing assay, and transwell migratory assay. H1650, H358, HCC827, H1299, H23, A549, H1693 were selected as human LUAD cell lines in the study. Results have shown that STEAP1 expression was up-regulated in LUAD cells compared with normal lung epithelial cells. Knockdowning of STEAP1 suppressed the proliferation, migration, and invasion of LUAD epithelial cells. Importantly, after comparing the proliferation, migration, and invasion of LUAD to the corresponding control groups treated in STAT3 inhibitor ADZ1480, we found that STEAP1 regulates EMT via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. In conclusion, STEAP1 can serve as a therapeutic target, and it may have important clinical implications for LUAD treatment.