KIAA1429 promotes gastric cancer progression by destabilizing RASD1 mRNA in an m6A-YTHDF2-dependent manner.

BACKGROUND: KIAA1429, a regulatory subunit of the N6-methyladenosine (m6A) methyltransferase complex, has been implicated in the progression of various cancers. However, the role of KIAA1429 in gastric cancer (GC) and its underlying mechanisms remain elusive. This study aimed to investigate the role of KIAA1429 in GC and to elucidate the underlying mechanisms. METHODS: The expression patterns and clinical relevance of KIAA1429 in GC were assessed using quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), and bioinformatic analysis. In vitro and in vivo loss- and gain-of-function assays, m6A dot blot assays, methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA-seq, MeRIP-qPCR, dual luciferase reporter assays, RNA stability assays, RNA immunoprecipitation (RIP) assays, and RNA pull-down assays were performed to investigate the biological functions and underlying molecular mechanisms of KIAA1429 in GC. RESULTS: Both the mRNA and protein expression of KIAA1429 were greater in GC tissues than in normal gastric tissues. High KIAA1429 expression correlated positively with poor prognosis in GC patients. KIAA1429 not only promoted GC cell proliferation, colony formation, G2/M cell cycle transition, migration, and invasion in vitro but also enhanced GC tumor growth and metastasis in vivo. Mechanistically, KIAA1429 increased the m6A level of RASD1 mRNA and enhanced its stability in an m6A-YTHDF2-dependent manner, thereby upregulating its expression. RASD1 knockdown partially rescued the KIAA1429 knockdown-induced impairment of pro­oncogenic ability in GC cells. The expression levels of KIAA1429 and RASD1 were negatively correlated in GC tissues. CONCLUSIONS: KIAA1429 plays a pro­oncogenic role in GC by downregulating RASD1 expression through destabilizing RASD1 mRNA in an m6A-YTHDF2-dependent manner. KIAA1429 may serve as a prognostic biomarker and therapeutic target for GC.

Unravelling the metabolic landscape of cutaneous melanoma: Insights from single-cell sequencing analysis and machine learning for prognostic assessment of lactate metabolism.

This manuscript presents a comprehensive investigation into the role of lactate metabolism-related genes as potential prognostic markers in skin cutaneous melanoma (SKCM). Bulk-transcriptome data from The Cancer Genome Atlas (TCGA) and GSE19234, GSE22153, and GSE65904 cohorts from GEO database were processed and harmonized to mitigate batch effects. Lactate metabolism scores were assigned to individual cells using the 'AUCell' package. Weighted Co-expression Network Analysis (WGCNA) was employed to identify gene modules correlated with lactate metabolism. Machine learning algorithms were applied to construct a prognostic model, and its performance was evaluated in multiple cohorts. Immune correlation, mutation analysis, and enrichment analysis were conducted to further characterize the prognostic model's biological implications. Finally, the function of key gene NDUFS7 was verified by cell experiments. Machine learning resulted in an optimal prognostic model, demonstrating significant prognostic value across various cohorts. In the different cohorts, the high-risk group showed a poor prognosis. Immune analysis indicated differences in immune cell infiltration and checkpoint gene expression between risk groups. Mutation analysis identified genes with high mutation loads in SKCM. Enrichment analysis unveiled enriched pathways and biological processes in high-risk SKCM patients. NDUFS7 was found to be a hub gene in the protein-protein interaction network. After the expression of NDUFS7 was reduced by siRNA knockdown, CCK-8, colony formation, transwell and wound healing tests showed that the activity, proliferation and migration of A375 and WM115 cell lines were significantly decreased. This study offers insights into the prognostic significance of lactate metabolism-related genes in SKCM.

HNRNPA2B1 stabilizes NFATC3 levels to potentiate its combined actions with FOSL1 to mediate vasculogenic mimicry in GBM cells.

BACKGROUND: Vasculogenic mimicry (VM) is an enigmatic physiological feature that influences blood supply within glioblastoma (GBM) tumors for their sustained growth. Previous studies identify NFATC3, FOSL1 and HNRNPA2B1 as significant mediators of VEGFR2, a key player in vasculogenesis, and their molecular relationships may be crucial for VM in GBM. AIMS: The aim of this study was to understand how NFATC3, FOSL1 and HNRNPA2B1 collectively influence VM in GBM. METHODS: We have investigated the underlying gene regulatory mechanisms for VM in GBM cell lines U251 and U373 in vitro and in vivo. In vitro cell-based assays were performed to explore the role of NFATC3, FOSL1 and HNRNPA2B1 in GBM cell proliferation, VM and migration, in the context of RNA interference (RNAi)-mediated knockdown alongside corresponding controls. Western blotting and qRT-PCR assays were used to examine VEGFR2 expression levels. CO-IP was employed to detect protein-protein interactions, ChIP was used to detect DNA-protein complexes, and RIP was used to detect RNA-protein complexes. Histochemical staining was used to detect VM tube formation in vivo. RESULTS: Focusing on NFATC3, FOSL1 and HNRNPA2B1, we found each was significantly upregulated in GBM and positively correlated with VM-like cellular behaviors in U251 and U373 cell lines. Knockdown of NFATC3, FOSL1 or HNRNPA2B1 each resulted in decreased levels of VEGFR2, a key growth factor gene that drives VM, as well as the inhibition of proliferation, cell migration and extracorporeal VM activity. Chromatin immunoprecipitation (ChIP) studies and luciferase reporter gene assays revealed that NFATC3 binds to the promoter region of VEGFR2 to enhance VEGFR2 gene expression. Notably, FOSL1 interacts with NFATC3 as a co-factor to potentiate the DNA-binding capacity of NFATC3, resulting in enhanced VM-like cellular behaviors. Also, level of NFATC3 protein in cells was enhanced through HNRNPA2B1 binding of NFATC3 mRNA. Furthermore, RNAi-mediated silencing of NFATC3, FOSL1 and HNRNPA2B1 in GBM cells reduced their capacity for tumor formation and VM-like behaviors in vivo. CONCLUSION: Taken together, our findings identify NFATC3 as an important mediator of GBM tumor growth through its molecular and epistatic interactions with HNRNPA2B1 and FOSL1 to influence VEGFR2 expression and VM-like cellular behaviors.

Quercetin ameliorates Helicobacter pylori-induced gastric epithelial cell injury by regulating specificity protein 1/lipocalin 2 axis in gastritis.

Helicobacter pylori (HP) infection is the main cause of most cases of gastritis. Quercetin has been shown to have anti-inflammatory, anti-bacterial, and antiviral activities and has been demonstrated to be involved in HP-induced gastric mucosa injury. Moreover, the secretory protein lipocalin-2 (LCN2) was elevated in HP-infected gastric mucosa. Thus, this work aimed to study the interaction between quercetin and LCN2 in HP-triggered gastric injury during gastritis. Human gastric epithelial cell line GES-1 cells were exposed to HP for functional experiments. Cell viability, apoptosis, and inflammation were evaluated by cell counting kit-8, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Levels of genes and proteins were tested using quantitative reverse transcription polymerase chain reaction and western blotting analyses. The interaction between LCN2 and specificity protein 1 (SP1) was validated using chromatin immunoprecipitation assay and dual-luciferase reporter assay. Thereafter, we found quercetin treatment suppressed HP-induced GES-1 cell apoptotic and inflammatory injury and macrophage M1 polarization. LCN2 was highly expressed in HP-infected gastritis patients and HP-infected GES-1 cells, while quercetin reduced LCN2 expression in HP-infected GES-1 cells; moreover, LCN2 knockdown reversed HP-induced GES-1 cell injury and macrophage M1 polarization, and forced expression of LCN2 abolished the protective effects of quercetin on GES-1 cells under HP infection. Mechanistically, SP1 bound to LCN2 promoter and promoted its transcription. Also, SP1 overexpression counteracted the functions of quercetin on HP-stimulated GES-1 cells. In all, quercetin ameliorated HP-induced gastric epithelial cell apoptotic and inflammatory injuries, and macrophage M1 polarization via the SP1/LCN2 axis.

PANoptosis-related signature in melanoma: Transcriptomic mapping and clinical prognostication.

Programmed cell death plays a pivotal role in maintaining tissue homeostasis, and recent advancements in cell biology have uncovered PANoptosis-a novel paradigm integrating pyroptosis, apoptosis, and necroptosis. This study investigates the implications of PANoptosis in melanoma, a formidable skin cancer known for its metastatic potential and resistance to conventional therapies. Leveraging bulk and single-cell transcriptome analyses, machine learning modeling, and immune correlation assessments, we unveil the molecular intricacies of PANoptosis in melanoma. Single-cell sequencing identifies diverse cell types involved in PANoptosis, while bulk transcriptome analysis reveals key gene sets correlated with PANoptosis. Machine learning algorithms construct a robust prognostic model, demonstrating consistent predictive power across diverse cohorts. Patients with different cohorts can be divided into high-risk and low-risk groups according to this PANoptosis score, with the high-risk group having a significantly worse prognosis. Immune correlation analyses unveil a link between PANoptosis and immunotherapy response, with potential therapeutic implications. Mutation analysis and enrichment studies provide insights into the mutational landscape associated with PANoptosis. Finally, we used cell experiments to verify the expression and function of key gene PARVA, showing that PARVA was highly expressed in melanoma cell lines, and after PARVA is knocked down, cell invasion, migration, and colony formation ability were significantly decreased. This study advances our understanding of PANoptosis in melanoma, offering a comprehensive framework for targeted therapeutic interventions and personalized medicine strategies in combating this aggressive malignancy.

Detection of botulinum neurotoxin A (BoNT/A) enzymatic activity by pregnancy test strips based on hCG-modified magnetic nanoparticles.

The detection of botulinum neurotoxin A (BoNT/A) endopeptidase activity by pregnancy test paper based on human chorionic gonadotropin (hCG)-functionalized peptide-modified magnetic nanoparticles (MNs) is described for the first time. HCG-functionalized SNAP-25 peptide substrate with hydrolysis recognition sites was optimally designed. HCG can be recognized by pregnancy test strips. BoNT/A light chain (BoNT-LcA) is the central part of the endopeptidase function in holotoxin, which can specifically hydrolyze SNAP-25 peptide to release the hCG-peptide probe, and the hCG-peptide probe released can be quantitatively detected by pregnancy test strips, achieving indirect determination of BoNT/A. By quantifying the T-line color intensity of test strips, the visual detection limit for BoNT-LcA is 12.5 pg/mL, and the linear range of detection for BoNT-LcA and BoNT/A holotoxin was 100 pg/mL to 1 ng/mL and 25 to 250 ng/mL. The ability of the method to quantify BoNT/A was validated in human serum samples. This method shows the potential for sensitive detecting BoNT/A and has prospects for the diagnosis and prognosis of clinical botulism.

eDNA reveals spatial homogenization of fish diversity in a mountain river affected by a reservoir cascade.

One of the main reasons for the decline in global freshwater biodiversity can be attributed to alterations in hydrological conditions resulting from dam construction. However, the majority of current research has focused on single or limited numbers of dams. Here, we carried out a seasonal fish survey, using environmental DNA (eDNA) method, on the Wujiang River mainstream (Tributaries of the Yangtze River, China) to investigate the impact of large-scale cascade hydropower development on changes in fish diversity patterns. eDNA survey revealed that native fish species have decreased in contrast to alien fish. There was also a shift in fish community structure, with declines of the dominant rheophilic fish species, an increase of the small-size fish species, and homogenization of species composition across reservoirs. Additionally, environmental factors, such as temperature, dissolved oxygen and reservoir age, had a significant effect on fish community diversity. This study provides basic information for the evaluation of the impact of cascade developments on fish diversity patterns.

Prognostic effects of the gastric mucosal microbiota in gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors with a high incidence and mortality. Microbiota play a significant role in human health and disease. We aimed to investigate the prognostic value of the gastric microbiota in different stomach microhabitats. We used our previously published 16S rRNA gene sequence data. We retrospectively enrolled a cohort of 132 patients with GC with complete prognostic information and selected 78 normal tissues, 49 peritumoral tissues, and 112 tumoral tissues for microbiota analysis. Patients with different prognoses showed different gastric microbiota compositions and diversity. The association network of the abundant gastric microbiota was more complicated in patients with poor prognoses. In the peritumoral microhabitat of patients with good prognoses, Helicobacter was significantly increased, whereas Halomonas and Shewanella were significantly decreased relative to that in the peritumoral microhabitat of patients with poor prognoses. PiCRUSt analysis revealed that the peritumoral microbiota had more different Kyoto Encyclopedia of Genes and Genomes pathways than did the tumoral and normal microbiota. This study evaluated the long-term prognostic value of the gastric mucosal microbiota in patients with GC. These findings suggested that the characteristic alterations of the gastric mucosal microbiota may be markers for clinical outcomes in these patients.

Esophageal anthracosis occurred after treatment of esophageal tuberculosis secondary to mediastinal tuberculous lymphadenitis: a rare case report.

BACKGROUND: Anthracosis is a disease generally considered to be in the lungs resulting from exposure to industrial dust in the workplace. Esophageal anthracosis is a fairly rare phenomenon and shows a strong correlation with tuberculosis. Moreover, esophageal involvement in tuberculosis is also rare. We here present an extremely rare case in which follow-up gastroesophageal endoscopy revealed a mass with a sunken, black area in the center and raised ring-like pattern in the surrounding mucosa resembling malignant melanoma. Uncovering the patient's tuberculosis history finally avoided a misdiagnosis or overtreatment. CASE PRESENTATION: A 67-year-old male patient was admitted to the hospital due to "repeated chest pain for 1 month". Endoscopic ultrasonography and contrast-enhanced CT scans revealed a mass adjacent to the esophageal wall with unclear boundaries. Aspiration biopsy confirmed that esophageal tuberculosis was caused by nearby mediastinal tuberculous lymphadenitis. After a standard anti-tuberculosis treatment regimen, the patient achieved a favorable prognosis. The follow-up gastroesophageal endoscopy showed a sunken black lesion with elevated peripheral mucosa replacing the original tuberculous mass, which was thought to be anthracosis, a disease that rarely occurs in the esophagus. CONCLUSION: The diagnosis of tuberculosis should be taken into consideration when a submucosal mass appears in the middle part of the esophagus. Endoscopic ultrasonography can effectively contribute to a definite diagnosis. Moreover, this is the first case of esophageal anthracosis observed only 1 year after the treatment of tuberculosis, indicating esophageal anthracosis can be a short-term disease. The traction of the reduction of tubercular mediastinal lymph nodes after anti-tuberculosis treatment may create a circumstance for pigmentation or dust deposition.

Prospective study of a new endoscopic duodenal-jejunal bypass sleeve in obese patients with nonalcoholic fatty liver disease (with video).

OBJECTIVES: To evaluate the safety and efficacy of a new endoscopic duodenal-jejunal bypass sleeve (DJBS) in obese patients with nonalcoholic fatty liver disease (NAFLD), while in situ for 3 months, and at 6 months postexplantation. METHODS: Patients with obesity and NAFLD were enrolled in this single-center, prospective study, wherein the TONGEE DJBS (Tangji Medical, Hangzhou, China) was implanted for 3 months. Primary outcomes were weight loss and changes in hepatic steatosis. Secondary outcomes included changes in liver enzymes, glycemic control, and lipid profile and device safety. RESULTS: Twenty-six patients (age 35.2 ± 7.2 years; 61.5% women) underwent DJBS implantation. At 3 months, bodyweight change from baseline was -8.0 ± 3.6 kg (P < 0.001), corresponding to 8.9 ± 4.0% of total bodyweight. Hepatic steatosis significantly improved based on controlled attenuation parameter, hepatic steatosis index, and fatty liver index (P < 0.001). Liver enzymes, insulin resistance, and metabolic parameters were also improved. At 6 months postexplantation, weight loss and improvements in hepatic steatosis and liver enzyme levels remained statistically significant. Only one patient had a serious adverse event, namely, upper gastrointestinal hemorrhage. CONCLUSIONS: Three-month TONGEE DJBS implantation resulted in significant weight loss and improvement in hepatic steatosis, liver enzymes, insulin resistance, and metabolic parameters in obese patients with NAFLD. Randomized controlled trials are required to further elucidate these initial findings.

Effect of Exogenous Plant Growth Regulators and Rejuvenation Measures on the Endogenous Hormone and Enzyme Activity Responses of Acer mono Maxim in Cuttage Rooting.

The cuttage rooting method for Acer species is difficult to achieve a good efficacy as trees maintain good characteristics at the rejuvenation stage, thus improving the rooting of Acer species. The addition of exogenous hormones and rejuvenation can improve the rooting effect of cuttings; however, the specific regulatory mechanism is still unclear. Here, Acer mono Maxim rejuvenation and non-rejuvenation cuttings were used as test subjects, to investigate the effects of exogenous hormones on the activities of endogenous hormones and antioxidant enzymes in the rooting process of young cuttings. The results showed that exogenous growth-regulating substances significantly improved the rooting rate of A. mono. Exogenous hormones naphthylacetic acid (NAA) + indolebutyric acid (IBA) increased the initial levels of the endogenous hormones, indoleacetic acid (IAA) and abscisic acid (ABA), and the enzyme activities of peroxidase (POD) and polyphenol oxidase (PPO). Rejuvenation treatment prolonged the time of increase in ABA content and indoleacetic acid oxidase (IAAO) activity at the root primordium induction stage, while increasing trans-zeatin riboside (ZR) content and decreasing POD enzyme activity in cuttings. These results demonstrate that A. mono cuttings can achieve the purpose of improving the rooting rate by adding the exogenous hormone (NAA + IBA), which is closely related to the changes of endogenous hormone content and enzyme activity, and these changes of A. mono rejuvenation cuttings are different from non-rejuvenation cuttings.

Bypassing large submucosal vessels during peroral endoscopic myotomy reduces operative time and intraoperative blood loss in patients with achalasia.

OBJECTIVE: Peroral endoscopic myotomy (POEM), a relatively, minimally invasive endoscopic procedure, is the first-line treatment for achalasia. The aim of this study is to compare procedure-related parameters and clinical outcomes between bypassing and performing prophylactic electrocoagulation of large submucosal vessels during POEM. METHODS: We retrospectively enrolled 112 patients with achalasia who had undergone POEM at our hospital between April 2017 and March 2023. Large submucosal vessels were bypassed to avoid injury during submucosal tunneling in the bypass group; whereas, large submucosal vessels were prophylactically treated by electrocoagulation in prophylactic electrocoagulation group. Procedure-related parameters, Eckardt score, and complications were compared between the two groups. RESULTS: The bypass group showed a significant reduction in the operative time and amount of intraoperative blood loss than prophylactic electrocoagulation group (37.11 ± 9.96 min vs. 58.80 ± 17.90 min, and 1 [interquartile range: 1-2] mL vs. 5 [interquartile range: 3-8] mL; P < 0.001). Eleven (17.5%) and 44 (89.8%) patients in the bypass and prophylactic electrocoagulation groups, respectively, required hemostatic forceps (P < 0.001). Furthermore, lower operative and hospitalization costs were recorded in the bypass group than those in prophylactic electrocoagulation group (P < 0.05). No statistically significant difference was found between the two groups in terms of submucosal tunnel length, myotomy length, clinical efficacy, or complications. CONCLUSIONS: Bypassing large submucosal vessels during POEM can reduce the operative duration and intraoperative blood loss, with no difference in clinical outcomes than the prophylactic electrocoagulation treatment.

A MSALL quantitative method for the determination of Poloxamer 188 in rat plasma by UHPLC-Q-TOF/MS and its application to pharmacokinetic study.

Poloxamer (PL)188 is a commonly used pharmaceutical excipient with unique physicochemical properties. In this study, an MSALL quantitative method for the determination of PL188 in rat plasma by UHPLC-Q-TOF/MS was developed and validated. PL188 was analyzed on PLRP-S reversed-phase column (50 × 4.6 mm, 8 µm, 1,000 Å) with mobile phase 0.1% formic acid-water and 0.1% formic acid in acetonitrile-isopropanol (2:3, v/v). The liner range was 0.1-10.0 µg/ml. A pharmacokinetic study was performed on rats at a dose of 5 mg/kg by intravenous injection. The pharmacokinetic parameters of intravenous injection were as follows: half-life was 2.0 ± 1.1 h, volume of distribution was 5.1 ± 3.2 L/kg, area under the concentration-time curve was 3.0 ± 0.6 µg/L h and clearance was 1.7 ± 0.3 L/h/kg. The results indicated that PL188 could be rapidly distributed to tissues with a high clearance rate. This study can provide a good reference for the further study of PL188.

Multiple resistance to ALS-inhibiting and PPO-inhibiting herbicides in Chenopodium album L. from China.

Common lambsquarters (Chenopodium album L.) is a broadleaf weed that can severely damage soybean fields. Two C. album populations (1744 and 1731) suspected resistant to imazethapyr were investigated for resistance levels to imazethapyr, thifensulfuron-methyl, and fomesafen and their resistance mechanisms were investigated. Whole-plant dose-response assays revealed that, compared to the susceptible (S) population, the 1744 population was 16.5-fold resistant to imazethapyr, slightly resistant to thifensulfuron-methyl (resistance index [R/S], <3). The 1731 population was 18.8-fold resistant to imazethapyr, 2.9-fold resistant to thifensulfuron-methyl, and 5.1-fold resistant to fomesafen. In vitro acetolactate synthase (ALS) assays showed 17.1-fold and 19.3-fold resistance levels of 1744 and 1731 populations to imazethapyr respectively. ALS gene sequence analysis identified Ala122Thr amino acid substitution in the 1744 population and Ser653Thr amino acid substitution in the 1731 population. No mutations of the protoporphyrinogen oxidase (PPO) gene were detected. However, pre-treatment with malathion reversed fomesafen resistance, suggesting nontarget-site resistance mechanisms likely play a role in the 1731 population.

Deficiency in the anti-apoptotic protein DJ-1 promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via p53.

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1-/- mice, DJ-1-/-p53-/- mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1-/- mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.

Vitamin D status and vitamin D receptor genotypes in celiac disease: a meta-analysis.

BACKGROUND: There have been various articles reporting relationship between Vitamin D (VitD) and celiac disease (CeD), but results remain controversial. This study aimed to conduct a meta-analysis to systematically review and quantify the relationship between VitD and CeD. Moreover, difference in Vitamin D Receptor (VDR) genotypes between CeD patients and controls was also analyzed. METHODS: Articles published until July 20, 2019 in the PubMed, MEDLINE, and EMBASE databases were searched. According to the inclusion and exclusion criteria, relevant statistical data were collated and extracted, which were finally analyzed by STATA15.1. RESULTS: 27 articles and 28 sets of data were included. It showed that average 25(OH)D level in CeD patients was 8.36 nmol/L lower than controls (Weighted Mean Difference (WMD) = -8.36, 95% CI = [-14.63, -2.09] nmol/L). After gluten-free diet treatment, we found that average 25(OH)D level in treated patients was 15.6 nmol/L higher than untreated patients (WMD = 15.6, 95% CI = [5.96, 25.23] nmol/L). In addition, 25(OH)D level in treated patients was close to healthy controls (WMD = -2.82, 95% CI = [-6.45, 0.73] nmol/L). However, genetic polymorphism analysis showed that there is no difference in VDR genotypes between CeD and control. CONCLUSIONS: CeD had decreased serum 25(OH)D levels, which returned to normal after treatment, suggesting that VitD may play a role in the development of CeD. The directionality of this association cannot be confirmed from cross-sectional studies. Demonstration of a causal role of VitD deficiency in CeD development in future studies could have important therapeutic implications.

Enhanced luminescence of Si(111) surface by localized surface plasmons of silver islands.

The role of silver localized surface plasmons (LSPs) on the luminescence of a Si(111)-(7 × 7) surface has been investigated by scanning tunneling microscopy (STM) with a silver tip at 77 K. On a bare Si(111)-(7 × 7) surface, a characteristic peak at 1.85 eV dominates the STM-induced luminescence spectrum, although the luminescence intensity is extremely weak. Once Ag atoms are deposited onto the Si surface to form islands with a few atomic layers, it is found that the intensity of the characteristic peak from the Si surface underneath the Ag islands is significantly enhanced by about one order. In addition to the luminescence from the Si surface, light emission originating from the irradiation decay of the Ag plasmons is also detected. Such great enhancement of the luminescence from the Si surface is attributed to the strong coupling between the surface states of the Si and the LSPs of the Ag islands.

Ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry method for quantifying polymer poloxamer 124 and its application to pharmacokinetic study.

Poloxamer is a commonly used pharmaceutical excipient. It is a high molecular polymer formed using polypropylene oxide and polyethylene oxide units. Specifically, poloxamer 124 is one of the smaller molecular weight in the poloxamer series; however, its pharmacokinetic behaviors in vivo are still unclear. In this study, a method for quantifying poloxamer 124 in rat plasma through ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry was developed. The intravenous dosage of PL124 was 10 mg/kg. Plasma was collected at different times. The calibration curve was linear in the range of 0.1-5 µg/mL for the poloxamer 124 (r ≥ 0.9956) with the lower limit of quantitation of 0.1 µg/ml. The relative standard deviation of the intraday and interday precisions was below 8.0%, and the relative error of the accuracy was within ±12.0%. The extraction recovery, matrix effect, and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of poloxamer 124 in rats. Results indicated that poloxamer 124 could be rapidly absorbed and eliminated through caudal vein injection. This study is helpful for the further study of poloxamer 124.

Tissue Distribution Study of Poloxamer188 in Rats by Ultra-High-Performance Liquid Chromatography Quadrupole Time of Flight/Mass Spectrometry with MSALL-Based Approach.

Poloxamer188 (PL188), as one of the most commonly used pharmaceutical excipients, has unique physicochemical properties and good biocompatibility, and so is playing an increasingly extensive role in the field of medicine. Currently, there are few studies on the tissue distribution of PL188 in vivo. In this study, the LC-MS method based on MSALL technique of quadrupole time of flight mass spectrometry for absolute quantitative analysis of poloxamer 188 in biological substrates was established for the first time. The tissue distribution of poloxamer188 in SD rats were studied using the established quantitative analysis method. To explore the distribution of PL188 in organs and tissues, PL188 was administered via rat tail vein at a dose of 5 mg/kg. Eight kinds of tissues including heart, liver, spleen, lung, kidney, stomach, muscle and brain of rats were collected at 0.25 h, 1 h and 4 h after administration. Tissue distributions showed the highest level was observed in kidney, then in stomach, which indicated PL188 mainly bioaccumulated in the kidney. This study can provide references for the further study of PL188.

Hypouricaemic and nephroprotective effects of Poria cocos in hyperuricemic mice by up-regulating ATP-binding cassette super-family G member 2.

CONTEXT: Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action. OBJECTIVE: To examine hypouricaemic action of Poria coco. MATERIALS AND METHODS: Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed. RESULTS: P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 µmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 µmol/L (p < 0.01) by PCE and 69 ± 23, 63 ± 15 and 62 ± 20 µmol/L (p < 0.01) by PCW, respectively. According to SCrs, BUNs and H&E staining, PCE and PCW partially attenuated renal dysfunction caused by HUA. They presented no negative effects on ALT, AST and ALP activities. They elevated ABCG2 (ATP-binding cassette super-family G member 2) mRNA and protein expression in comparison to HUA control. In molecular docking, compound 267, 277, 13824, 15730 and 5759 were predicted as the top bioactives of P. cocos against HUA, which even presented better scores than the positive compound, oestrone 3-sulfate. DISCUSSION AND CONCLUSIONS: This paper demonstrated the hypouricaemic and nephroprotective effects of P. cocos in hyperuricemic mice by up-regulating ABCG2. These results may be useful for the development of a hypouricaemic agent.