Dedifferentiation-like reprogramming of degenerative nucleus pulposus cells into notochordal-like cells by defined factors.

The extensive degeneration of functional somatic cells and the depletion of endogenous stem/progenitor populations present significant challenges to tissue regeneration in degenerative diseases. Currently, a cellular reprogramming approach enabling directly generating corresponding progenitor populations from degenerative somatic cells remains elusive. The present study focused on intervertebral disc degeneration (IVDD) and identified a three-factor combination (OCT4, FOXA2, TBXT [OFT]) that could induce the dedifferentiation-like reprogramming of degenerative nucleus pulposus cells (dNPCs) toward induced notochordal-like cells (iNCs). Single-cell transcriptomics dissected the transitions of cell identity during reprogramming. Further, OCT4 was found to directly interact with bromodomain PHD-finger transcription factor to remodel the chromatin during the early phases, which was crucial for initiating this dedifferentiation-like reprogramming. In rat models, intradiscal injection of adeno-associated virus carrying OFT generated iNCs from in situ dNPCs and reversed IVDD. These results collectively present a proof-of-concept for dedifferentiation-like reprogramming of degenerated somatic cells into corresponding progenitors through the development of a factor-based strategy, providing a promising approach for regeneration in degenerative disc diseases.

Metastatic Small-Cell Lung Carcinoma Infiltrating the Heart: A Rare Case Diagnosed Using Imaging Data.

Small-cell lung carcinoma is a high-grade aggressive disease that occurs most commonly in bronchial lung cancer, and metastasis to the heart is extremely rare. The diagnosis of metastatic small-cell lung carcinoma infiltrating the heart remains challenging because of the variability of its clinical presentation. Hereinafter, we reported a case of a 41-year-old man who suffered from small-cell lung cancer that invaded the pulmonary artery. The patient presented with chest tightness, dry cough, and deterioration in exercise tolerance and diagnosed at his imaging data, who had an uneventful recovery after surgical resection of the masses.

Effect of High-Intensity vs Low-Intensity Noninvasive Positive Pressure Ventilation on the Need for Endotracheal Intubation in Patients With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease: The HAPPEN Randomized Clinical Trial.

Importance: The effect of high-intensity noninvasive positive pressure ventilation (NPPV) on the need for endotracheal intubation in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) is unknown. Objective: To determine whether the use of high-intensity NPPV vs low-intensity NPPV reduces the need for endotracheal intubation in patients with an acute exacerbation of COPD and hypercapnia. Design, Setting, and Participants: Randomized clinical trial conducted at 30 general respiratory non-intensive care unit wards of Chinese hospitals from January 3, 2019, to January 31, 2022; the last 90-day follow-up was on April 22, 2022. The included patients had an acute exacerbation of COPD and a Paco2 level greater than 45 mm Hg after receiving 6 hours of low-intensity NPPV. Interventions: Patients were randomized 1:1 to receive high-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume 10 mL/kg to 15 mL/kg of predicted body weight (n = 147) or to continue receiving low-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume of 6 mL/kg to 10 mL/kg of predicted body weight (n = 153). Patients in the low-intensity NPPV group who met the prespecified criteria for the need for endotracheal intubation were allowed to crossover to high-intensity NPPV. Main Outcomes and Measures: The primary outcome was the need for endotracheal intubation during hospitalization, which was defined by prespecified criteria. There were 15 prespecified secondary outcomes, including endotracheal intubation. Results: The trial was terminated by the data and safety monitoring board and the trial steering committee after an interim analysis of the first 300 patients. Among the 300 patients who completed the trial (mean age, 73 years [SD, 10 years]; 68% were men), all were included in the analysis. The primary outcome of meeting prespecified criteria for the need for endotracheal intubation occurred in 7 of 147 patients (4.8%) in the high-intensity NPPV group vs 21 of 153 (13.7%) in the low-intensity NPPV group (absolute difference, -9.0% [95% CI, -15.4% to -2.5%], 1-sided P = .004). However, rates of endotracheal intubation did not significantly differ between groups (3.4% [5/147] in the high-intensity NPPV group vs 3.9% [6/153] in the low-intensity NPPV group; absolute difference, -0.5% [95% CI, -4.8% to 3.7%], P = .81). Abdominal distension occurred more frequently in the high-intensity NPPV group (37.4% [55/147]) compared with the low-intensity NPPV group (25.5% [39/153]). Conclusions and Relevance: Patients with COPD and persistent hypercapnia in the high-intensity NPPV group (vs patients in the low-intensity NPPV group) were significantly less likely to meet criteria for the need for endotracheal intubation; however, patients in the low-intensity NPPV group were allowed to crossover to high-intensity NPPV, and the between-group rate of endotracheal intubation was not significantly different. Trial Registration: ClinicalTrials.gov Identifier: NCT02985918.

Preparation, Characterization, and Oral Bioavailability of Solid Dispersions of Cryptosporidium parvum Alternative Oxidase Inhibitors.

The phenylpyrazole derivative 5-amino-3-[1-cyano-2-(3-phenyl-1H-pyrazol-4-yl) vinyl]-1-phenyl-1H-pyrazole-4-carbonitrile (LN002), which was screened out through high-throughput molecular docking for the AOX target, exhibits promising efficacy against Cryptosporidium. However, its poor water solubility limits its oral bioavailability and therapeutic utility. In this study, solid dispersion agents were prepared by using HP-ß-CD and Soluplus® and characterized through differential scanning calorimetry, Fourier transform infrared, powder X-ray diffraction, and scanning electron microscopy. Physical and chemical characterization showed that the crystal morphology of LN002 transformed into an amorphous state, thus forming a solid dispersion of LN002. The solid dispersion prepared with an LN002/HP-ß-CD/Soluplus® mass ratio of 1:3:9 (w/w/w) exhibited significantly increased solubility and cumulative dissolution. Meanwhile, LN002 SDs showed good preservation stability under accelerated conditions of 25 °C and 75% relative humidity. The complexation of LN002 with HP-ß-CD and Soluplus® significantly improved water solubility, pharmacological properties, absorption, and bioavailability.

Reductive sequestration of Cr (VI) by phosphorylated nanoscale zerovalent iron.

The cracked phosphorylated nanoscale zerovalent iron (p-nZVI) has a strong electron selectivity towards the reductive removal of many heavy metal ions in waters. However, the unintended environmental risk after interactions with impurities or wastewater are not involved. Therefore, in this study, the phosphate group was successfully adsorbed into p-nZVI, and the cracked p-nZVI was successfully prepared with an optimal P/Fe ratio of 0.5%. The dosages of p-nZVI and temperatures were positively correlated with the removal rates. The removal process of Cr(VI) was more suitable by the Langmuir isothermal model（R2 > 0.99). The process of Cr (VI) (10, 20 and 40 mg/L) removal more fitted the pseudo first-order reaction model, while the process of Cr (VI) (60, 80 mg/L) removal more fitted the pseudo second-order reaction model. The Cr (VI) removal rates gradually decreased when the pH was increased. Dissolved oxygen slowed nanoiron reaction rates. The order of inhibition on the reactivity towards Cr(VI) was SiO32- > SO42- > PO43- > NO3- > HCO3-.The facilitation followed the order of Cd2+>Cu2+>Mg2+>Mn2+>Ca2+. Ca2+ showed an inhibitory effect, but all other cations showed different degrees of facilitation. The promotion effect is relatively similar in presence of Mn2+ or Mg2+. HA had a significant inhibitory effect. Environmental friendly p-nZVI had a good effect in simulated groundwater, seawater, river water and secondary effluent of the urban sewage treatment plant. The main pathway to remove Cr (VI) was in situ reduction by p-nZVI. The improved adsorption and reduction effect of p-nZVI on heavy metal ions in water was due to the structural change and the phosphate group.

Farmland phytoremediation in bibliometric analysis.

Phytoremediation is an environmentally friendly, economical, and sustainable technique for restoring farmland. It can remove heavy metals and organic pollutants from the soil through the implementation of hyperaccumulator plants. In recent years, it has garnered significant interest from academic and industrial sectors. This article screened 368 research papers from the Web of Science core collection database related to farmland phytoremediation and conducted a bibliometric analysis of the domain based on CiteSpace. The paper intuitively demonstrates the most influential countries, the most productive institutions, the most contributing groups of authors, and the primary sources of farmland phytoremediation research domain. The findings additionally indicate that the research hotspots include: (1) mechanisms and principles of phytoremediation, (2) the improvement of restoration efficiency, (3) the economic, ecological, and sustainable development of phytoremediation. The exploration of plants with potential to accumulate heavy metals and produce large amounts of biomass is the research frontier within the field of farmland phytoremediation. Additionally, this bibliometric analysis can help scholars willing to work in this research field by concisely understanding the overall research field and frontiers. With the continuous improvement of phytoremediation and its combination with other remediation technologies, the future of farmland remediation will have a promising prospect.

Effectiveness and Influencing Factors of Home-Center-Based Cardiac Rehabilitation as a Transitional Strategy for Acute Myocardial Infarction Patients.

Currently, providing patients, particularly those with acute myocardial infarction (AMI), with comprehensive cardiac rehabilitation (CR) has been challenging because of the inadequate availability of medical resources in developing countries. To ensure balance between disease instability and early rehabilitation, strategies for facilitating professional and comprehensive CR opportunities for patients with AMI must be explored.A prospective cohort study was carried out on 1,533 patients with AMI who were admitted to a tertiary hospital between July 2018 and October 2019. Following the principle of voluntarism, 286 patients with AMI participated in home-center-based CR (HCB group), whereas 1,247 patients received usual care (UC group). The primary endpoint of this study was the occurrence of cardiovascular events at 30 months after AMI. Moreover, the study analyzed factors that influence participation rate and effectiveness of the CR model.After analysis, a significant difference in the occurrence of cardiovascular endpoints between the HCB group and the UC group was observed (harzard ratio, 0.68 [95%CI, 0.51-0.91], P = 0.008), with participation in home-center-based CR being an independent influencing factor. Multivariate regression analysis revealed age, gender, smoking history, triglyceride levels, and ejection fraction as independent factors that influence participation rate. Female gender, peak oxygen uptake per kilogram body weight, and ventilation/carbon dioxide production slope were identified as factors that affect the effectiveness of the CR model.In the context of developing countries, this study demonstrates that the home-center-based CR model is efficient and analyzes factors that influence participation rate and effectiveness of the model. These findings provide practical insights for further development of CR programs.

Effect of Lacticaseibacillus paracasei K56 with galactooligosaccharide synbiotics on obese individuals: an in vitro fermentation model.

BACKGROUND: The use of synbiotics is emerging as a promising intervention strategy for regulating the gut microbiota and for preventing or reducing obesity, in comparison with the use of probiotics or prebiotics alone. A previous in vivo study revealed that Lacticaseibacillus paracasei K56 (L. paracasei K56) could alleviate obesity induced in high-fat-diet mice; however, the effect of the synbiotic combination of L. paracasei K56 and prebiotics in obese individuals has not been explored fully. RESULTS: The effect of prebiotics on the proliferation of L. paracasei K56 was determined by spectrophotometry. The results showed that polydextrose (PG), xylooligosaccharide (XOS), and galactooligosaccharide (GOS) had a greater potential to be used as substrates for L. paracasei K56 than three other prebiotics (melitose, stachyose, and mannan-oligosaccharide). An in vitro fermentation model based on the feces of ten obese female volunteers was then established. The results revealed that K56_GOS showed a significant increase in GOS degradation rate and short-chain fatty acid (SCFA) content, and a decrease in gas levels, compared with PG, XOS, GOS, K56_PG, and K56_XOS. Changes in these microbial biomarkers, including a significant increase in Bacteroidota, Bifidobacterium, Lactobacillus, Faecalibacterium, and Blautia and a decrease in the Firmicutes/Bacteroidota ratio and Escherichia-Shigella in the K56_GOS group, were associated with increased SCFA content and decreased gas levels. CONCLUSION: This study demonstrates the effect of the synbiotic combination of L. paracasei K56 and GOS on obese individuals and indicates its potential therapeutic role in obesity treatment. © 2024 Society of Chemical Industry.

siGCD: a web server to explore survival interaction of genes, cells and drugs in human cancers.

It is pivotal and remains challenge for cancer precision treatment to identify the survival outcome interactions between genes, cells and drugs. Here, we present siGCD, a web-based tool for analysis and visualization of the survival interaction of Genes, Cells and Drugs in human cancers. siGCD utilizes the cancer heterogeneity to simulate the manipulated gene expression, cell infiltration and drug treatment, which overcomes the data and experimental limitations. To illustrate the performance of siGCD, we identified the survival interaction partners of EGFR (gene level), T cells (cell level) and sorafenib (drug level), and our prediction was consistent with previous reports. Moreover, we validate the synergistic effect of regorafenib and glyburide, and found that glyburide could significantly improve the regorafenib response. These results demonstrate that siGCD could benefit cancer precision medicine in a wide range of advantageous application scenarios including gene regulatory network construction, immune cell regulatory gene identification, drug (especially multiple target drugs) response biomarker screening and combination therapeutic design.

Immune index: A gene and cell prognostic signature for immunotherapy response prediction in hepatocellular carcinoma.

The heterogeneity of tumor immune microenvironment (TIME) plays important roles in the development and immunotherapy response of hepatocellular carcinoma (HCC). Using machine learning algorithms, we introduced the immune index (IMI), a prognostic model based on the HCC immune landscape. We found that IMI low HCCs were enriched in stem cell and proliferating signatures, and yielded more TP53 mutation and 17p loss compared with IMI high HCCs. More importantly, patients with high IMI exhibited better immune-checkpoint blockade (ICB) response. To facilitate clinical application, we employed machine learning algorithms to develop a gene model of the IMI (IMIG), which contained 10 genes. According to our HCC cohort examination and single-cell level analysis, we found that IMIG high HCCs exhibited favorable survival outcomes and high levels of NK and CD8+ T cells infiltration. Finally, after coculture with autologous tumor infiltrating lymphocytes, IMIG high tumor cells exhibited a better response to nivolumab treatment. Collectively, the IMI and IMIG may serve as powerful tools for the prognosis, classification and ICB treatment response prediction of HCC.

Efficacy and safety of non-prostanoid prostacyclin receptor agonist for pulmonary hypertension: A meta-analysis.

BACKGROUND: Oral non-prostanoid prostacyclin receptor agonists therapies have been recommended for pulmonary arterial hypertension in many countries. OBJECTIVE: We aimed to evaluate the specific impact of non-prostanoid prostacyclin receptor agonists on pulmonary hypertension and to explore the influence of study characteristics on results. METHODS: PubMed, Embase, and ClinicalTrials.gov were systematically searched from inception to July 12, 2022. Randomized controlled trials comparing non-prostanoid prostacyclin receptor agonists administration with placebo for treating pulmonary hypertension were included. Two researchers independently selected eligible studies, assessed the bias risk and extracted related data. RevMan5.1 was used for performing the statistical analysis and the assessment of bias risk of the enrolled studies. PROSPERO registered number CRD42022304172. RESULTS: Seven trials involving 1727 patients were included. Pooled analyses indicated non-prostanoid prostacyclin receptor agonists significantly reduced clinical worsening events (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.54 to 0.74), increased 6-min walk distance (mean difference [MD], 10 m; 95% CI, 3-17 m), decreased pulmonary vascular resistance (MD, -121 dyn s/cm5; 95% CI, -172 to -69 dyn s/cm5) and increased cardiac index (MD, 0.38 L/min/m2; 95% CI, 0.26-0.50 L/min/m2) compared with the control. No significant differences in all-cause mortality (RR, 0.86; 95% CI, 0.26 to 2.78), NYHA/WHO functional class (RR, 1.16; 95% CI, 0.61 to 2.18), mean pulmonary artery pressure (MD, -0.88 mmHg; 95% CI, -2.20 to 0.44 mmHg), right atrial pressure (MD, 0.66 mmHg; 95% CI, -0.59 to 1.90 mmHg) and total adverse events (RR, 1.05; 95% CI, 0.99 to 1.10) were found between non-prostanoid prostacyclin receptor agonists group and control group. CONCLUSION: Non-prostanoid prostacyclin receptor agonists treatment exerted benefits on clinical worsening, pulmonary vascular resistance, and cardiac index in pulmonary hypertension patients, without increasing the incidence of total adverse events.

Short-term effect of particulate matter on lung function and impulse oscillometry system (IOS) parameters of chronic obstructive pulmonary disease (COPD) in Beijing, China.

OBJECTIVE: This study aimed to evaluate the associations between particulate matter (PM), lung function and Impulse Oscillometry System (IOS) parameters in chronic obstructive pulmonary disease (COPD) patients and identity effects between different regions in Beijing, China. METHODS: In this retrospective study, we recruited 1348 outpatients who visited hospitals between January 2016 and December 2019. Ambient air pollutant data were obtained from the central monitoring stations nearest the participants' residential addresses. We analyzed the effect of particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) exposure on lung function and IOS parameters using a multiple linear regression model, adjusting for sex, smoking history, education level, age, body mass index (BMI), mean temperature, and relative humidity . RESULTS: The results showed a relationship between PM2.5, lung function and IOS parameters. An increase of 10 µg/m3 in PM2.5 was associated with a decline of 2.083% (95% CI: -3.047 to - 1.103) in forced expiratory volume in one second /predict (FEV1%pred), a decline of 193 ml/s (95% CI: -258 to - 43) in peak expiratory flow (PEF), a decline of 0.932% (95% CI: -1.518 to - 0.342) in maximal mid-expiratory flow (MMEF); an increase of 0.732 Hz (95% CI: 0.313 to 1.148) in resonant frequency (Fres), an increase of 36 kpa/(ml/s) (95% CI: 14 to 57) in impedance at 5 Hz (Z5) and an increase of 31 kpa/(ml/s) (95% CI: 2 to 54) in respiratory impedance at 5 Hz (R5). Compared to patients in the central district, those in the southern district had lower FEV1/FVC, FEV1%pred, PEF, FEF75%, MMEF, X5, and higher Fres, Z5 and R5 (p < 0.05). CONCLUSION: Short-term exposure to PM2.5 was associated with reductions in lung function indices and an increase in IOS results in patients with COPD. The heavier the PM2.5, the more severe of COPD.

B-Raf inhibitor vemurafenib counteracts sulfur mustard-induced epidermal impairment through MAPK/ERK signaling.

The chemical warfare agent sulfur mustard (SM) causes severe cutaneous lesions characterized by epidermal cell death, apoptosis, and inflammation. At present, the molecular mechanisms underlying SM-induced injury are not well understood, and there is no standard treatment protocol for SM-exposed patients. Here, we conducted a high-content screening of the Food and Drug Administration (FDA)-approved drug library of 1018 compounds against SM injury on an immortal human keratinocyte HaCaT cell line, focusing on cell survival. We found that the B-Raf inhibitor vemurafenib had an apparent therapeutic effect on HaCaT cells and resisted SM toxicity. Other tested B-Raf inhibitors, both type-I (dabrafenib and encorafenib) and type-II (RAF265 and AZ628), also exhibited potent therapeutic effects on SM-exposed HaCaT cells. Both SM and vemurafenib triggered extracellular signal-related kinase (ERK) activation. The therapeutic effect of vemurafenib in HaCaT cells during SM injury was ERK-dependent, indicating a specific role of ERK in keratinocyte regulatory mechanisms. Furthermore, vemurafenib partially improved cutaneous damage in a mouse ear vesicant model. Collectively, our results provide evidence that the B-Raf inhibitor vemurafenib is a potential therapeutic agent against SM injury, and oncogenic B-Raf might be an exciting new therapeutic target following exposure to mustard vesicating agents.

Cardiac lipoma in left ventricle: A rare case diagnosed using imaging data.

Lipomas occuring within the heart are rare tumors, and invasive cardiac lipomas are even rare. Hereinafter we reported a case of a 51-year-old woman with a left ventricular transmural invasive lipoma, and summarized the imaging characteristics and main sites of it. Comprehensive imaging investigations appears valuable for early detection, intraoperative monitoring, and postoperative follow-up of invasive cardiac lipomas.

Metabolite Identification of Isopropoxy Benzene Guanidine in Rat Liver Microsomes by Using UHPLC-Q-TOF-MS/MS.

Isopropoxy benzene guanidine (IBG) is a guanidine derivative with antibacterial activity against multidrug-resistant bacteria. A few studies have revealed the metabolism of IBG in animals. The aim of the current study was to identify potential metabolic pathways and metabolites of IBG. The detection and characterization of metabolites were performed with high-performance liquid chromatography tandem mass spectrometry (UHPLC-Q-TOF-MS/MS). Seven metabolites were identified from the microsomal incubated samples by using the UHPLC-Q-TOF-MS/MS system. The metabolic pathways of IBG in the rat liver microsomes involved O-dealkylation, oxygenation, cyclization, and hydrolysis. Hydroxylation was the main metabolic pathway of IBG in the liver microsomes. This research investigated the in vitro metabolism of IBG to provide a basis for the further pharmacology and toxicology of this compound.

Preparation and Antimicrobial Activity of a Film-Forming Polyhexamethylene Biguanide Teat Disinfectant.

Bovine mastitis caused by infectious pathogens can lead to a decline in production performance and an increase in elimination rate, resulting in huge losses to the dairy industry. This study aims to prepare a novel dairy cow teat disinfectant with polyhexamethylene biguanide (PHMB) as the main bactericidal component and to evaluate its bactericidal activity in vitro and its disinfection effect in dairy cow teats. PHMB disinfectant with a concentration of 3 g/L was prepared with PVA-1788, propylene glycol and glycerol as excipients. When the dilution ratio is 1:4800 and the action time is 5 min, the PHMB teat disinfectant can reduce the four types of bacteria (S. agalactiae ATCC 12386, S. dysgalactiae ATCC 35666, S. aureus ATCC 6538, and E. coli ATCC 8099) by 99.99%. PHMB teat disinfectant applied on the skin of rabbits with four bacteria types achieved an average log10 reduction greater than 4. After 30 s of PHMB teat disinfectant dipping, the bacteria of cow teats were counted prior to disinfection. The mean log10 reduction in bacteria on the skin surface of 12 cows ranged from 0.99 to 3.52 after applying the PHMB teat disinfectant for 10 min. After 12 h, the PHMB teat disinfectant achieved an average log10 reduction in bacteria from 0.27 to 0.68 (compared with that prior to disinfection). These results suggested that PHMB teat disinfection has the potential to prevent and treat mastitis-causing bacteria in dairy herds.

Deep learning applications for the accurate identification of low-transcriptional activity drugs and their mechanism of actions.

Analysis of drug-induced expression profiles facilitated comprehensive understanding of drug properties. However, many compounds exhibit weak transcription responses though they mostly possess definite pharmacological effects. Actually, as a representative example, over 66.4% of 312,438 molecular signatures in the Library of Integrated Cellular Signatures (LINCS) database exhibit low-transcriptional activities (i.e. TAS-low signatures). When computing the association between TAS-low signatures with shared mechanism of actions (MOAs), commonly used algorithms showed inadequate performance with an average area under receiver operating characteristic curve (AUROC) of 0.55, but the computation accuracy of the same task can be improved by our developed tool Genetic profile activity relationship (GPAR) with an average AUROC of 0.68. Up to 36 out of 74 TAS-low MOAs were well trained with AUROC ≥ 0.7 by GPAR, higher than those by other approaches. Further studies showed that GPAR benefited from the size of training samples more significantly than other approaches. Lastly, in biological validation of the MOA prediction for a TAS-low drug Tropisetron, we found an unreported mechanism that Tropisetron can bind to the glucocorticoid receptor. This study indicated that GPAR can serve as an effective approach for the accurate identification of low-transcriptional activity drugs and their MOAs, thus providing a good tool for drug repurposing with both TAS-low and TAS-high signatures.

Site prioritization and performance assessment of groundwater monitoring network by using information-based methodology.

The arbitrary distribution of groundwater monitoring sites and the redundancy of observation data restrict the ability of monitoring network to provide reliable and effective data information. The purpose of this study is aimed at finding a quantitative method to screen ideal monitoring locations and evaluate the efficiency of the monitoring network. In terms of site selection, we use hydrogeological information, monitoring density and monitoring location to select the suitable site to monitor groundwater quality, understand the temporal trends and identify the abnormal signals of pollution sources. To evaluate the efficiency of monitoring network we used the groundwater quality data for consecutive years to evaluate the groundwater monitoring network based on information entropy and principal component analysis (PCA). The results show that the optimized groundwater monitoring network is comprised of 10 monitoring wells. The efficiency evaluation results of information entropy and PCA are basically consistent. The maximum mutual information (T) and comprehensive index of monitoring site (Laiguangying) were 1.29 and 3.25 respectively, while the minimum T and comprehensive index of monitoring site (Jinzhan) were 1.05 and -0.36 respectively, and the data efficiency was low. This study provides a good example for optimizing a groundwater pollution monitoring network.

Modeling drug mechanism of action with large scale gene-expression profiles using GPAR, an artificial intelligence platform.

BACKGROUND: Querying drug-induced gene expression profiles with machine learning method is an effective way for revealing drug mechanism of actions (MOAs), which is strongly supported by the growth of large scale and high-throughput gene expression databases. However, due to the lack of code-free and user friendly applications, it is not easy for biologists and pharmacologists to model MOAs with state-of-art deep learning approach. RESULTS: In this work, a newly developed online collaborative tool, Genetic profile-activity relationship (GPAR) was built to help modeling and predicting MOAs easily via deep learning. The users can use GPAR to customize their training sets to train self-defined MOA prediction models, to evaluate the model performances and to make further predictions automatically. Cross-validation tests show GPAR outperforms Gene set enrichment analysis in predicting MOAs. CONCLUSION: GPAR can serve as a better approach in MOAs prediction, which may facilitate researchers to generate more reliable MOA hypothesis.

Reduced D-Serine Release May Contribute to Impairment of Long-Term Potentiation by Corticosterone in the Perforant Path-Dentate Gyrus.

Long-term potentiation (LTP) is a neurobiological mechanism of cognitive function, and the N-methyl-D-aspartate (NMDA) receptors is fundamental for LTP. Previous studies showed that over activation of NMDA receptors may be a crucial cause of LTP and cognitive impairment induced by stress or corticosterone. However, other studies showed that the function of NMDA receptors is insufficient since the NMDA receptors co-agonist D-serine could improve stress-induced cognitive impairment. The purpose of this study is to clarify whether over activation of NMDA receptors or hypofunction of NMDA receptors is involved in hippocampal impairment of LTP by corticosterone and the underlying mechanisms. Results showed that hippocampal LTP and object location recognition memory were impaired in corticosterone-treated mice. Corticosterone increased the glutamate level in hippocampal tissues, neither NMDA receptors antagonist nor its subtype antagonists alleviated impairment of LTP, while enhancing the function of NMDA receptors by D-serine did alleviate impairment of LTP by corticosterone, suggesting that hypofunction of NMDA receptors might be one of the main reasons for impairment of LTP by corticosterone. Further results showed that the level of D-serine and its precursor L-serine did not change. D-serine release-related protein Na+-independent alanine-serine-cysteine transporter-1 (ASC-1) in the cell membrane was decreased and increasing D-serine release by the selective activator of ASC-1 antiporter activity alleviated impairment of LTP by corticosterone. Taken together, this study demonstrates that hypofunction of NMDA receptors may be involved in impairment of LTP by corticosterone and reduced D-serine release may be an important reason for its hypofunction, which is an important complement to existing mechanisms of corticosterone-induced LTP and cognitive impairment.