Serum-volatile organic compounds in the diagnostics of esophageal cancer.

The early diagnosis of esophageal cancer (EC) is extremely challenging due to a lack of effective diagnostic methods. The study presented herein aims to assess whether serum volatile organic compounds (VOCs) could be utilised as emerging diagnostic biomarkers for EC. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect VOCs in the serum samples of 55 patients with EC, with samples from 84 healthy controls (HCs) patients analysed as a comparison. All machine learning analyses were based on data from serum VOCs obtained by GC-IMS. A total of 33 substance peak heights were detected in all patient serum samples. The ROC analysis revealed that four machine learning models were effective in facilitating the diagnosis of EC. In addition, the random forests model for 5 VOCs had an AUC of 0.951, with sensitivities and specificities of 94.1 and 96.0%, respectively.

Active components and mechanisms of total flavonoids from Rhizoma Drynariae in enhancing cranial bone regeneration: An investigation employing serum pharmacochemistry and network pharmacology approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Drynariae, as the dried rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., is a traditional Chinese medicine for treating the injury and bone broken of falling and beating. Total flavonoids is considered as the major and effective compounds for the therapeutic efficacy of Rhizoma Drynariae. AIM OF THE STUDY: To explore the effect of total flavonoids from Rhizoma Drynariae (TFRD) on bone regeneration and the underlying mechanisms. MATERIALS AND METHODS: The effect of TFRD in various doses on bone reconstruction in cranial bone defect rats was explored in vivo. The active ingredients in TFRD-medicated serum were characterized by serum pharmacochemistry and integrated by network pharmacology analysis and target prediction. To elucidate the underlying mechanism of TFRD on bone regeneration, experimental validation in vitro was executed to assess the influence of different concentrations of TFRD-medicated serum on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). RESULTS: Micro-CT, histological examination, immunohistochemical analysis, and ELSA demonstrated that administration of TFRD could promote bone reconstruction in a rat cranial defect model. We identified 27 active components of TFRD using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Results from CCK8, ALP, and Alizarin Red S staining revealed that TFRD-medicated serum notably enhanced BMSCs proliferation and osteogenic differentiation. qRT-PCR and Western blot harvested results consistent with those predicted by network pharmacology, providing further evidence that TFRD activated the TGF-ß signaling pathway to benefit bone regeneration. CONCLUSION: The active components of TFRD modulate the TGF-ß signaling pathway to facilitate osteogenesis, thereby repairing cranial bone defects.

Identification of urinary volatile organic compounds as a potential non-invasive biomarker for esophageal cancer.

Early diagnosis of esophageal cancer (EC) is extremely challenging. The study presented herein aimed to assess whether urinary volatile organic compounds (VOCs) may be emerging diagnostic biomarkers for EC. Urine samples were collected from EC patients and healthy controls (HCs). Gas chromatography-ion mobility spectrometry (GC-IMS) was next utilised for volatile organic compound detection and predictive models were constructed using machine learning algorithms. ROC curve analysis indicated that an 8-VOCs based machine learning model could aid the diagnosis of EC, with the Random Forests having a maximum AUC of 0.874 and sensitivities and specificities of 84.2% and 90.6%, respectively. Urine VOC analysis aids in the diagnosis of EC.

The integrated production of hydrochar and methane from lignocellulosic fermentative residue coupling hydrothermal carbonization with anaerobic digestion.

The popularization of large-scale biogas project makes the disposal of fermentative residue an urgent issue to be solved. Hydrothermal carbonization (HTC) technology is suitable for treating wet biomass to produce carbonaceous materials. In this study, the solid residue from the two-phase anaerobic digestion (AD) was hydrothermally converted in the range of 180-240 °C, and the hydrochar and aqueous components were characterized for subsequent utilization. The heating values of hydrochar were indicated to be increased by 14.2% and 16.6% at 210 °C and 240 °C as compared with feedstock, and also the specific surface areas were 34.8 m2/g and 27.1 m2/g with 17.4- and 13.3-fold enhancement, respectively. The migration of elements such as S, Cl, K to aqueous phase was beneficial for fuel application. The mesoporous pores were dominant in hydrochars with ample oxygenated functional groups. In addition, the wastewater involved organic acids, phenols, and nitrogen-containing compounds, etc. Evaluating the biodegradability by AD, it was found that when the initial concentration was ≤8 g COD/L, the maximum methane yields up to 275.9 mL CH4/g CODremoval and 277.6 mL CH4/g CODremoval were obtained. The enhanced toxicity/inhibition of representative pollutants on microorganisms was significant at higher organic loading, which could be indicated in the microbial structure and diversity. As a conclusion, the integrated production of hydrochar and methane will provide an extended route for further processing of lignocellulosic fermentative residue.

Volatile organic compounds for early detection of prostate cancer from urine.

Prostate cancer (PCa) is one of the most common cancers in men worldwide. Early diagnosis of PCa is extremely challenging due to the lack of effective diagnostic methods. The study presented here aims to evaluate whether urine volatile organic compounds (VOCs) can be used as an emerging diagnostic biomarker for PCa. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect VOCs in urine samples from 66 patients with PCa and to comparatively analyze samples from 87 patients with non-cancerous controls (NCs). A total of 86 substance peak heights were detected in urine samples from all patients. Analysis using four machine learning algorithms suggested that the diagnosis of PCa could be effectively facilitated. Ultimately, diagnostic models were constructed based on the four VOCs selected. The AUC for the RF and SVM model were 0.955 and 0.981, respectively. Both the NN and DT diagnostic models also achieved an AUC of 0.8 or more, but their sensitivity or specificity was poor compared to the RF and SVM models.

Dual effects of ultrasound on fabrication of anodic aluminum oxide.

Ultrasound has been proven to enhance the mass transfer process and impact the fabrication of anodic aluminum oxide (AAO). However, the different effects of ultrasound propagating in different media make the specific target and process of ultrasound in AAO remain unclear, and the effects of ultrasound on AAO reported in previous studies are contradictory. These uncertainties have greatly limited the application of ultrasonic-assisted anodization (UAA) in practice. In this study, the bubble desorption and mass transfer enhancement effects were decoupled based on an anodizing system with focused ultrasound, such that the dual effects of ultrasound on different targets were distinguished. The results showed that ultrasound has the dual effects on AAO fabrication. Specifically, ultrasound focused on the anode has a nanopore-expansion effect on AAO, leading to a 12.24 % improvement in fabrication efficiency. This was attributed to the promotion of interfacial ion migration through ultrasonic-induced high-frequency vibrational bubble desorption. However, AAO nanopores were observed to shrink when ultrasound was focused on the electrolyte, accompanied by a 25.85 % reduction in fabrication efficiency. The effects of ultrasound on mass transfer through jet cavitation appeared to be the reason for this phenomenon. This study resolved the paradoxical phenomena of UAA in previous studies and is expected to guide AAO application in electrochemistry and surface treatments.

Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential.

Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.

CD36 regulates LPS-induced acute lung injury by promoting macrophages M1 polarization.

M1 polarization of macrophages works as a promoter in pathogenesis of acute lung injury / acute respiratory distress syndrome (ALI/ARDS) by the secretion of pro-inflammatory cytokines and recruiting other inflammatory cells. Lipopolysaccharide (LPS), a critical component of the wall of gram-negative bacteria, can induce M1 polarization and ALI. Recently, cluster of differentiation 36 (CD36) has been reported to be associated with inflammatory responses. However, it has not yet been clarified whether CD36 in macrophages is involved in LPS-induced ALI. Herein, we demonstrated that in macrophages, LPS-induced ALI was regulated by CD36. Loss of CD36 attenuated LPS-induced ALI by reducing M1 polarization. Mechanistically, CD36 promoted macrophage M1 polarization by regulating CD14 associated with TLR4 during LPS stimulation. The findings of this study, clarified the mechanism of LPS-induced ALI through CD36 in macrophages, which provides a potential target for the prevention and treatment of ALI.

Aryl hydrocarbon receptor nuclear translocator promotes the proliferation and invasion of clear cell renal cell carcinoma cells potentially by affecting the glycolytic pathway.

Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that has been reported to play a vital role in regulating glycolysis, angiogenesis and apoptosis. Recently, ARNT has been reported to a play role in pancreatic-islet function in type 2 diabetes. However, the role of ARNT in kidney cancer has not yet been investigated. In the present study, ARNT expression was detected in tissues from patients with renal cell carcinoma (RCC) and in RCC cell lines. Oncomine, The Cancer Genome Atlas and cBioPortal were used to investigate the roles of ARNT in RCC. Cell migration and invasion assays were used to explore the molecular mechanisms involved. It was found that ARNT protein expression was elevated both in tissues from patients with clear cell RCC (ccRCC) and in different RCC cell lines. ARNT disruption using siRNA knockdown inhibited the migratory abilities and cell proliferation, potentially by altering the glycolysis pathway in vitro, as evidenced by decreased M2 type acetone kinase, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 and hexokinase 2 expression. Taken together, the findings in the present study revealed a novel function of ARNT in ccRCC and indicated that ARNT promotes the proliferation and invasion of ccRCC, possibly through changes to the glycolytic pathway.

Comparison of methanogenic potential of wood vinegar with gradient loads in batch and continuous anaerobic digestion and microbial community analysis.

Anaerobic digestion (AD) of wood vinegar wastewater (WVWW) has considerable potential in energy recovery and sustainable development. WVWW contains abundant acetic acid and some refractory organics. Therefore, the batch and continuous AD of WVWW were investigated. The threshold value of the inhibitory concentration was obtained at a chemical oxygen demand (COD) of 4 g/L in batch AD. Three-dimensional electrolysis was adopted to improve the biodegradability of WVWW, and a reduction in the inhibitory rate from 38.2% to 4.9% and an increase in methane production by 53.8% were observed. The up-flow anaerobic sludge blanket reactor achieved an efficient conversion of methane at an organic loading rate (OLR) of <8.58 g COD/L·d. However, the OLR of 10.01 g COD/L·d decreased the methane production from 350.6 to 42.5 mL CH4/g CODfed. Aminicenantales, Acetobacterium, Anaerolineae, and SBR1031 were the dominant bacterial genera in continuous AD. Fewer genera with similar classifications were detected in the batch AD. In the archaea community, acetotrophic methanogens (Methanosaeta) dominated and increased continuously with increasing OLR. Microbial analysis revealed that toxic substances affected bacterial diversity and promoted the enrichment of Intestinimonas, Syntropobacter, and Propionicimonas at high OLRs. The continuous AD was most suitable for the energy recovery from WVWW.

Neuroprotective Effects of Fluoxetine Against Chronic Stress-Induced Neural Inflammation and Apoptosis: Involvement of the p38 Activity.

Depression is considered a widespread neuropsychiatric disease associated with neuronal injury within specific brain regions. Fluoxetine, a selective serotonin reuptake inhibitor, has been widely used in depressed patients. Recently, fluoxetine has demonstrated neuroprotective effects apart from the effect on serotonin. However, the underlying mechanism involved in this neuroprotection remains unclear, in particular, whether fluoxetine exerts antidepressant effects via protecting against neuronal injury. Here, we found that treatment with fluoxetine (10 mg/kg, i.p.) for 2 weeks ameliorated depression-like behaviors in a chronic unpredictable mild stress (CUMS)-induced rat model of depression and was accompanied with an alleviation of glia activation and inhibition of interleukin-1ß (IL-1ß), interferon gamma (IFN-γ), and tumor necrosis factor-α (TNF-α) expression in the hippocampal dentate gyrus (DG) region. Meanwhile, CUMS rats treated with fluoxetine showed reductions in neuronal apoptosis and a downregulation of the apoptotic protein Bax, cleaved caspase 3, and caspase 9 levels. These effects appear to involve a downregulation of p38 mitogen-activated protein kinase (MAPK) signaling within the DG hippocampus as the specific inhibitor of p38 MAPK, SB203580, significantly suppressed apoptosis, as well as ameliorated depressive behaviors resulting from CUMS exposure. Moreover, fluoxetine could rescue neuronal deterioration and depression-like phenotypes caused by overexpression of p38 in DG. This finding extends our knowledge on the antidepressant-like effects of fluoxetine, which appear to at least partially profit from neuroprotection against inflammation and neuronal apoptosis via downregulation of the p38 MAPK pathway. The neuroprotective mechanisms of fluoxetine may provide some novel therapeutic avenues for stress-related neurological diseases.

Inhibitor of Differentiation 1 (ID1) Facilitates the Efficacy of Sorafenib in Non-Small Cell Lung Cancer Cells through Suppressing Epithelial to Mesenchymal Transition.

BACKGROUND Sorafenib, which is a multitargeted kinase inhibitor, has shown some antitumor effects in patients with non-small cell lung cancer (NSCLC). However, the potential target of sorafenib's antitumor activity is largely unknown. Moreover, definitive predictive biomarkers of benefit have rarely been reported. MATERIAL AND METHODS The alteration in inhibitor of differentiation 1 (ID1) expression in NSCLC cells with sorafenib treatment was detected by western blotting. The sensitivity of NSCLC cells to sorafenib was observed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay. Loss-of-function and gain-of-function experiments were performed to observe the role of ID1 expression in epithelial to mesenchymal transition (EMT) progression. RESULTS Initially, we observed that ID1 was downregulated in NSCLC cells treated with sorafenib. The response of NSCLC cells to sorafenib was inhibited by the transfection of small interfering RNAs (siRNAs) targeting ID1. In contrast, the transfection of ID1-overexpressing plasmids improved the response of NSCLC cells to sorafenib. Further experiments indicated that ID1 is expressed at high levels in epithelial H460 cells and expressed at low levels in mesenchymal H358 cells. Loss-of-function and gain-of-function experiments suggested that ID1 negatively regulates EMT in NSCLC. CONCLUSIONS The expression of ID1 is dose-dependently inhibited by sorafenib, and the overexpression of ID1 contributes to the antitumor activity of sorafenib by suppressing EMT development. Our results indicate that ID1 might be a potential target for the antitumor activity of sorafenib in NSCLC and that targeting ID1 is a feasible strategy to improve the sensitivity of NSCLC cells to sorafenib.

Acidogenic and methanogenic properties of corn straw silage: Regulation and microbial analysis of two-phase anaerobic digestion.

Corn straw silage (CSS) is one of the organic solid residues available for biogas production. The aim of this study was to investigate the possibility and optimal controlling strategy for anaerobic digestion (AD) of CSS. Four leaching bed reactors (LBR) were operated at different pH. Maximum volatile fatty acids (VFAs) concentration of 19.34 g/L was reached at pH 8.0 with acetic and propionic acids as dominant VFAs. The subsequent microbial analysis indicated that abundant bacteria were Firmicutes, Bacteroidetes and Proteobacteria. UASB as methanogenic reactor was integrated with the LBR. The organic loading rate (OLR) could reach 8 g COD/L·d with effective conversion of VFAs. Acetotrophic Methanosaeta and hydrogenotrophic Methanobacterium played major roles in methanogenic process. In the whole process, the results showed that methane yield of 143.4 mL CH4/g volatile solid (VS) was obtained. pH and OLR controls in two-phase AD were feasible for methane production from CSS.

Enhancing the anaerobic digestion of corn stover by chemical pretreatment with the black liquor from the paper industry.

In this work, black liquor as a waste from paper industry was used to pretreat corn stover before anaerobic digestion. The batch mode anaerobic digestion achieved a methane production up to 260.5 mL/g VS when the corn stover was pretreated the black liquor of 12 g NaOH/L alkalinity for 24 h, which was 59.1% higher than the control. In the semi-continuous mode anaerobic digestion, black liquor pretreatment increased the buffering capacity of the digestate to maintain suitable pH and total VFA/alkalinity ratio with no adverse effect resulted from the presence of ions. The structural and chemical changes of corn stover after the pretreatment were investigated to rationalize the enhanced performance of anaerobic digestion.

Association between bile acid metabolism and bone mineral density in postmenopausal women

OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.

Anticonvulsant effect of gentamicin on the seizures induced by kainic acid.

OBJECTIVE:  Epilepsy is a chronic neurological disorder affecting approximately 0.5-2% of the population worldwide. Gentamicin (GM) is an aminoglycoside antibiotic used to treat several types of bacterial infections. We investigate whether the administration of GM can reduce seizures in temporal lobe epilepsy (TLE). METHODS: The animal model of temporal lobe epilepsy (TLE) was established by kainic acid (KA) intrahippocampal injection. Behavioral test and Electroencephalography (EEG) recordings were performed to detect the effects of GM on the seizures triggered by KA injection in rats. Furthermore, immunofluorescence was used to investigate the influence of GM on the c-fos expression in the hippocampus. RESULTS:  Here we found that the intracerebroventricular administration of GM is able to prevent the seizures induced by intrahippocampal kainic acid (KA) injection. Behaviorally, the latent period to the first seizure was significantly prolonged by GM. GM can totally abolish the occurrence of stage IV or V seizures and prominently reduce the total seizure duration. Electrographic recording showed that the latent period to the first seizure, the number and duration of high-amplitude, high-frequency discharges were remarkably reduced by GM. Additionally, the expression of c-fos was significantly decreased in the ipsilateral hippocampus of KA-injected rats treated with GM compared with KA-injected rats treated with saline. CONCLUSION:  These findings could promote the understanding of the pharmacological effects of GM, enriching the application of gentamicin in clinical practice.

Parkinson's disease-like forelimb akinesia induced by BmK I, a sodium channel modulator.

Parkinson's disease (PD) is a neurodegenerative disorder and characterized by motor disabilities which are mostly linked with high levels of synchronous oscillations in the basal ganglia neurons. Voltage-gated sodium channels (VGSCs) play a vital role in the abnormal electrical activity of neurons in the globus pallidus (GP) and the subthalamic nucleus (STN) in PD. BmK I, a α-like toxin purified from the Chinese scorpion Buthus martensi Karsch, has been identified a site-3-specific modulator of VGSCs. The present study shows that forelimb akinesia can be induced by the injection of BmK I into the globus pallidus (GP) in rats. In addition, BmK I cannot produce neuronal damage in vivo and in vitro at 24h after treatment, indicating that the forelimb akinesia does not result from neuronal damage. Electrophysiological studies further revealed that the inactivated Na(+) currents were showed to be more vulnerably modulated by BmK I than the activated Na(+) currents in human neuron-like SHSY5Y cells. Furthermore, the modulation of BmK I on inactivation was preferentially attributed to fast inactivation rather than slow inactivation. Therefore, the PD-like forelimb akinesia may result from the modulation of sodium channels in neuron by BmK I. These findings not only suggest that BmK I may be an effective and novel molecule for the study of pathogenesis in PD but also support the idea that VGSCs play a crucial role in the motor disabilities in PD.

A new process for efficiently producing methane from waste activated sludge: alkaline pretreatment of sludge followed by treatment of fermentation liquid in an EGSB reactor.

In the literature the production of methane from waste activated sludge (WAS) was usually conducted in a continuous stirred tank reactor (CSTR) after sludge was pretreated. It was reported in our previous publication that compared with other pretreatment methods the methane production in CSTR could be significantly enhanced when sludge was pretreated by NaOH at pH 10 for 8 days. In order to further improve methane production, this study reported a new process for efficiently producing methane from sludge, that is, sludge was fermented at pH 10 for 8 days, which was adjusted by Ca(OH)(2), and then the fermentation liquid was treated in an expanded granular sludge bed (EGSB) for methane generation. First, for comparing the methane production observed in this study with that reported in the literature, the conventional operational model was applied to produce methane from the pH 10 pretreated sludge, that is, directly using the pH 10 pretreated sludge to produce methane in a CSTR. It was observed that the maximal methane production was only 0.61 m(3)CH(4)/m(3)-reactor/day. Then, the use of fermentation liquid of pH 10 pretreated sludge to produce methane in the reactors of up-flow anaerobic sludge bed (UASB), anaerobic sequencing batch reactor (ASBR) and EGSB was compared. The maximal methane production in UASB, ASBR, and EGSB reached 1.41, 3.01, and 12.43 m(3)CH(4)/m(3)-reactor/day, respectively. Finally, the mechanisms for EGSB exhibiting remarkably higher methane production were investigated by enzyme, adenosine-triphosphate (ATP), scanning electron microscope (SEM) and fluorescence in situ hybridization (FISH) analyses. It was found that the granular sludge in EGSB had the highest conversion efficiency of acetic acid to methane, and the greatest activity of hydrolysis and acidification enzymes and general physiology with much more Methanosarcinaceae.