Large-scale prediction of stream water quality using an interpretable deep learning approach.

Deep learning methods, which have strong capabilities for mapping highly nonlinear relationships with acceptable calculation speed, have been increasingly applied for water quality prediction in recent studies. However, it is argued that the practicality of deep learning methods is limited due to the lack of physical mechanics to explain the prediction results of water quality changes. A knowledge gap exists in rationalizing the deep learning results for water quality predictions. To address this gap, an interpretable deep learning framework was established to predict the spatiotemporal variations of water quality parameters in a large spatial region. Mereological, land-use, and socioeconomic variables were adopted to predict the daily variations of stream water quality parameters across 138 sub-catchments in a total of over 575,250 km2 in southern China. The coefficients of determination of chemical oxygen demand (COD), total phosphorus (TP), and total nitrogen (TN) predictions were over 0.80, suggesting a satisfactory prediction performance. The model performance in terms of prediction accuracy could be improved by involving land-use and socioeconomic predictors in addition to hydrological variables. The SHapley Additive exPlanations method used in this study was demonstrated to be effective for interpreting the prediction results by identifying the significant variables and reasoning their influencing directions on the variation of each water quality parameter. The air temperature, proportion of forest area, grain production, population density, and proportion of urban area in each sub-catchment as well as the accumulated rainfall within the previous 3 days were identified as the most significant variables affecting the variations of dissolved oxygen, COD, ammoniacal nitrogen(NH3-N), TN, TP, and turbidity in the stream water in the case area, respectively.

Antidepressant Activity of Euparin: Involvement of Monoaminergic Neurotransmitters and SAT1/NMDAR2B/BDNF Signal Pathway.

Depression is the most significant risk factor for suicide, yet the causes are complex and disease mechanism remains unclear. The incidence and disability rate of depression are very high and the efficacy of some traditional antidepressants is not completely satisfactory. Recently, some studies have found that benzofurans have anti-oxidation and anti-monoamine oxidase properties, which are related to depression. Euparin is a monomer compound of benzofuran, previous work by our team found that it improves the behavior of depressed mice. However, additional antidepressant effects and mechanisms of Euparin have not been reported. In this study, the Chronic Unpredictable Mild Stress (CUMS) model of mice was used to further investigate the effect and mechanism of Euparin on depression. Results showed that Euparin (8, 16 and 32 mg/kg) reduced depression-like behavior in mice compared with the model group. Meanwhile, all doses of Euparin were found to increase the contents of monoamine neurotransmitter and decrease monoamine oxidase and reactive oxygen species (ROS) levels in brain of depression mice. Additionally, Euparin restored CUMS-induced decrease of Spermidine/Spermine N1-Acetyltransferase 1 (SAT1), N-methyl-D-aspartate receptor subtype 2B (NMDAR2B) and brain derived neurotrophic factor (BDNF) expression. These findings demonstrate that Euparin has antidepressant properties, and its mechanism involves the SAT1/NMDAR2B/BDNF signaling pathway.

Effect of different phosphorus concentrations on biodiesel production from Isochrysis zhangjiangensis under nitrogen sufficiency or deprivation condition.

The effects of two nitrogen (N) concentrations combining with three phosphorus (P) concentrations on Isochrysis zhangjiangensis growth and formation of fatty acid (FA) were investigated in this study. Biomass concentration, mass fraction, and productivity of FA in I. zhangjiangensis were low in N-deprived media. Under both N and P sufficiency conditions, the intake of P and N was 40 times and 4.7 times of the normal algal growth condition, respectively, indicating I. zhangjiangensis had the potential for removing P and N from high concentrated N and P salinity wastewater. This study also showed that P deficiency in N sufficient medium increased the FA content, however, the difference between P limitation and P deprivation was not significant (P > 0.05). In N sufficient and P limitation medium, FA productivity was the highest, with a composition suitable for biofuel, so, this condition was the optimal condition for biodiesel production from I. zhangjiangensis.

[Preparation and in vitro evaluation of arsenic trioxide glioma targeting drug delivery system loaded by PAMAM dendrimers co-modified with RGDyC and PEG].

Arsenic trioxide (ATO) is an effective component of traditional Chinese medicine arsenic. The existing studies have shown its good inhibition and apoptosis ability on a variety of tumours. However, its toxicity and difficulties in the permeability into the blood brain barrier (BBB) has the limitation in the application of glioma treatment. Polyamide-amine dendrimer (PAMAM) is a synthetic polymer with many advantages, such as a good permeability, stability and biocompatibility. Additionally, the 5th generation of PAMAM is an ideal drug carrier due to its three-dimensional structure. In this study, the 5th generation of PAMAM co-modified with RGDyC and PEG, then confirmed by ¹H-NMR. The average particle size of nanoparticles was about 20 nm according to the nanoparticle size-potential analyser and transmission electron microscopy. in vitro release showed that the nanocarrier not only has the sustained release effect, but also some pH-sensitive properties. The cell results showed that PAMAM co-modified with RGDyC and PEGAM has a lower cytotoxicity than the non-modified group in vitro. Accordingly, the drug delivery system has a better anti-tumour effect across the blood brain barrier (BBB) in vitro, which further proves the tumour targeting of RGDyC.

Study on antidepressant effect and mechanism of self-made prescription of strengthening spleen and replenishing Qi / 中国药理学通报

Aim To explore the antidepressant effect and the mechanism of self-made prescription of strengthening spleen and replenishing Qi ( SMP-SS-RQ) . Methods The depression model of chronic un-predictable mild stress ( CUMS ) was established in mice. The animals were randomly divided into control group, model group, SMP-SSRQ low, middle and high dose groups (8, 16, 32 mg·kg-1), with 12 mice for each group. The control group and the model group were given the same volume of saline, and other groups were given corresponding dose of SMP-SSRQ. Animals of each group were administered by gavage twice a day for two weeks. Behavioral indexes of mice were deter-mined by open field experiment, sugar consumption test, forced swimming test and tail suspension test. Quantitative real-time PCR (qPCR) and Western blot were respectively performed to detect mRNA and pro-tein expression levels of Igsf11 , Pdia2 and Sec14 l2 inprefrontal cortex and hippocampus. Results Com-pared with model group, depressed mice' s horizontal mobile score, upright number and the sugar water pref-erence index increased and FST as well as TST de-creased in all SMP-SSRQ groups(P<0.05). The de-pression symptoms in mice were obviously improved by SMP-SSRQ therapy. Low and high doses of SMP-SSRQ significantly reduced mRNA and protein expression lev-el of Igsf11 , Pdia2 and Sec14 l2 in the prefrontal cortex and hippocampus of the depressed mice, presenting significant statistical difference compared with model group ( P<0.05 ) . Conclusions SMP-SSRQ can ef-fectively improve mouse depressive behavior, and its mechanism may be related to the down-regulation of Igsf11 , Pdia2 and Sec14 l2 in mouse prefrontal cortex and hippocampus.

[Effect of Baihu Guizhi decoction on characteristic methylation genes expression of pyretic arthralgia rat model].

To investigate the characteristic methylation genes of pyretic arthralgia model in hot and dampness environment and the regulation effect of Baihu Guizhi decoction on this characteristic methylation genes. Plantar injection of CFA was used in hot and dampness environment to induce the pyretic arthralgia rat models. From 15th day after modeling, Baihu Guizhi decoction was given for 30 days. Foot volume was detected every 4 days after modeling, and HE staining was used to detect the histopathology of all rats' ankle joint at day 45.MeDIP-Seq sequencing method was used to detect the methylation level of knee joint synovial, and the method of difference sets was used to screen the characteristic methylation genesinpyretic arthralgia models.The contents of IL-1ß, IL-17, TNF-α, EGF, IL-12p70, IL-4, IL-6 and IFN-γ in serum were measured by using suspension chips. The mRNA expression level of characteristic methylation genes was measured by qRT-PCR. The results suggested that as compared with adjuvant arthritis rat models(AA), the foot swelling and histopathology inpyretic arthralgia models (PA) were only slightly increased. As compared with normal group (NG), the wholegenome CpG island in both AA and PA groups was kept in a lower methylation state, furthermore, the methylation level was lowest in PA group; with 705 difference methylation genes in AA group and 2 418 difference methylation genes in PA group. As compared with AA, there were 1 287 difference methylation genes, including 974 down-regulated methylation genesand 313 up-regulated methylation genes. This difference methylation genes were mostly enriched in 32 KEGG pathways. Moreover, there were 52 characteristic methylation genes of PA models in promoter region, including 36 down-regulatedmethylation genes and 16 up-regulatedmethylation genes. After drug intervention, Baihu Guizhi decoction improved the foot swelling and pathological injury in PA models, significantly decreased the levels of IL-1ß, TNF-α, EGF, VEGF, IL-17, IL-12p70, inhibited the mRNA expression levels of down-regulated methylation genes AHCY and RPL3, and promoted the mRNA expression levels of up-regulated methylation gene Agxt. In conclusion, unique methylation changes of synovial genes were present in PA models, and Baihu Guizhi decoction may adjust the methylation level of PA's characteristic methylation genes to achieve the therapeutic effect of pyretic arthralgia.

Elevation of n-3/n-6 PUFAs ratio suppresses mTORC1 and prevents colorectal carcinogenesis associated with APC mutation.

Although epidemiological and preclinical studies have shown the preventative effect of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC), the underlying molecular mechanisms are not clear. In this study, we revealed that elevation of n-3/n-6 PUFAs ratio suppress the mechanistic target of rapamycin complex 1 (mTORC1) and prevent colorectal tumorigenesis. The transgenic expression of fat-1, a desaturase that catalyzes the conversion of n-6 to n-3 PUFAs and produces n-3 PUFAs endogenously, repressed colorectal tumor cell growth and remarkably reduced tumor burden, and alleviated anemia as well as hyperlipidemia in APCMin/+ (adenomatous polyposis coli) mice, a classic CRC model that best simulates most clinical cases. In contrast to arachidonic acid (AA, C20:4 n-6), either Docosahexaenoic acid (DHA, C22:6 n-3), eicosapentaenoic acid (EPA, C20:5 n-3), or a combination of DHA and AA, efficiently inhibited the proliferation of CRC cell lines and promoted apoptosis in these cells. The ectopic expression of fat-1 had similar effects in colon epithelial cells with APC depletion. Mechanistically, elevation of n-3/n-6 ratio suppressed mTORC1 activity in tumors of APCMin/+ mice, CRC cell lines with APC mutation, and in normal colon epithelial cells with APC depletion. In addition, elevation of n-3/n-6 ratio repressed mTORC1 activity and inhibited adipogenic differentiation in preadipocytes with APC knockdown, as well as alleviated hyperlipidemia in APCMin/+ mice. Taken together, our findings have provided novel insights into the potential mechanism by which increase in n-3/n-6 PUFAs ratio represses CRC development, and also a new rationale for utilizing n-3 PUFAs in CRC prevention and treatment.

Role of sufficient phosphorus in biodiesel production from diatom Phaeodactylum tricornutum.

In order to study the role of sufficient phosphorus (P) in biodiesel production by microalgae, Phaeodactylum tricornutum were cultivated in six different media treatments with combination of nitrogen (N) sufficiency/deprivation and phosphorus sufficiency/limitation/deprivation. Profiles of N and P, biomass, and fatty acids (FAs) content and compositions were measured during a 7-day cultivation period. The results showed that the FA content in microalgae biomass was promoted by P deprivation. However, statistical analysis showed that FA productivity had no significant difference (p = 0.63, >0.05) under the treatments of N deprivation with P sufficiency (N-P) and N deprivation with P deprivation (N-P-), indicating P sufficiency in N deprivation medium has little effect on increasing biodiesel productivity from P. triornutum. It was also found that the P absorption in N-P medium was 1.41 times higher than that in N sufficiency and P sufficiency (NP) medium. N deprivation with P limitation (N-P-l) was the optimal treatment for producing biodiesel from P. triornutum because of both the highest FA productivity and good biodiesel quality.

Role of oxidative stress in surgical cavernous nerve injury in a rat model.

This study investigates the role of oxidative stress in surgical cavernous nerve (CN) injury in a rat model. Eighty-four male Sprague-Dawley rats were randomly divided into three groups: group 1, sham-operated rats; group 2, bilateral CN-crushed rats; and group 3, bilateral CN-transection-and-sutured-immediately rats. Oxidative stress was evaluated by malondialdehyde levels, super oxide dismutase (SOD) activities, and glutathione peroxidase (GPX) activities in serum. Erectile function was assessed by CN electrostimulation at 3 months with mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure. Nerve injury was assessed by toluidine blue staining of CNs and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining of penile tissue. GPX protein expression and nitrotyrosine-3 (NT-3) levels in penile tissue were measured. Erectile function and the number of myelinated axons of CNs and NADPH-diaphorase-positive nerve fibers were statistically decreased between groups, from sham to crush to transection. For markers, both nerve-injury groups showed increased oxidative stress markers at early time points, with the transection group showing greater oxidative stress than the crushed group and values normalizing to sham levels by week 12. GPX expression and NT-3 levels in penile tissue were in concordance with the results of SOD and GPX. These results show that oxidative stress plays an important role in injured CNs, and different methods of CN injury can lead to different degrees of oxidative stress in a rat model.

[Optimization of Formulation of Panax notoginseng Saponins Transfersomes].

OBJECTIVE: To optimize the formulation of Panax notoginseng saponins (PNS) transfersomes. METHODS: PNS transfersomes were prepared by film hydration-dispersion process. Based on the entrapment efficiency (EE) of ginsenoside Rg1 and ginsenoside Rb1, the effects of formulated quantity of sodium deoxycholate and cholesterol, the relative ion strength and pH value of hydration liquid were investigated. The formulation of PNS transfersomes were optimized by single-factor experiment and uniform design experiment. The in vitro characteristics of the optimized transfersomes were evaluated. RESULTS: The optimum formulation were as follows: egg phospholipid 0.45 g, cholesterol 0.05 g,vitamin E 0.01 g, sodium deoxycholate 0.119 g, PNS 0.1 g,10 mL of hydration liquid with pH at 4.75 (a mixture of 0.1 mol/L citric acid solution and 0.2 mol/L disodium orthophosphate solution, which corresponded to appropriate ion strength). The optimized PNS transfersomes had an average size of (121.8 ± 3.9) nm with a PDI of 0.136 ± 0.007 and a Zeta potential of (-8. 24 ± 0. 63) mV. The EE of ginsenoside Rg1 and ginsenoside Rb1 was 88.0% and 98.7% respectively. CONCLUSION: The formulation of PNS transfersomes can be optimized by uniform design experiment combined with single-factor experiment.

Inhibition of endometrial cancer by n-3 polyunsaturated fatty acids in preclinical models.

Although preclinical and epidemiologic studies have shown the importance of n-3 polyunsaturated fatty acids (PUFA) in the prevention of hormone-responsive cancers such as breast cancer, evidence of the association between n-3 PUFAs and endometrial cancer risk is limited and no previous study has examined the effect of n-3 PUFAs on endometrial cancer in cellular and animal models. In this study, we demonstrated that docosahexenoic acid (DHA) dose- and time-dependently inhibited endometrial cancer cell proliferation, colony formation, and migration and promoted apoptosis. Dietary n-3 PUFAs efficiently prevented endometrial cancer cell growth in xenograft models. Moreover, ectopic expression of fat-1, a desaturase, catalyzed the conversion of n-6 to n-3 PUFAs and produced n-3 PUFAs endogenously, also suppressed endometrial tumor cell growth and migration, and potentiated apoptosis in endometrial cancer cell lines. Interestingly, implanted endometrial cancer cells were unable to grow in fat-1 transgenic SCID mice. Further study revealed that mTOR signaling, which plays an essential role in cell proliferation and endometrial tumorigenesis, is a target of n-3 PUFAs. Exogenous or endogenous n-3 PUFAs efficiently suppressed both mTOR complex 1 (mTORC1) and mTORC2 in vitro and in vivo. Moreover, both dietary n-3 PUFAs and transgenic expression of fat-1 in mice effectively repressed mTORC1/2 signaling and endometrial growth elicited by unopposed estrogen. Taken together, our findings provide comprehensive preclinical evidences that n-3 PUFAs efficiently prevent endometrial cancer and establish mTORC1/2 as a target of n-3 PUFAs.

[Study on relations between characteristics of traditional chinese medicine body constitutions and syndromes in COPD patients].

The specific theoretical system of traditional Chinese medicine(TCM) body constitutions had beening gradually founded, which showed TCM body constitutions comprehensively and introduced the clinical treatment. According to TCM body constitutions, it was benefit to recognize and prevent diseases through investigating the susceptible body and discussing the relation between constitutions and syndromes, and since TCM body constitutions leaded the characteristic of susceptibility and tendency of diseases and the body was stable but changed later. TCM body constitutions of 498 COPDs were diagnosed by questionnaires and the relation between the constitutions and syndromes were analyzed. The result showed that the constitutions of Qi asthenia, of phlegm-dampness and of damp-heat were common constitutions in COPDs. There was a significant correlation between TCM body constitutions and syndromes. Thus, during different period of COPD taking the treatment of adjusting the constitutions especially biased constitutions and combining "recognizing constitutions" and "recognizing syndromes" are benefit to increase the effect of prevention and treatment, and are significant to decrease the incidence and prevalence.

Study on relations between characteristics of traditional chinese medicine body constitutions and syndromes in COPD patients / 中国中药杂志

The specific theoretical system of traditional Chinese medicine(TCM) body constitutions had beening gradually founded, which showed TCM body constitutions comprehensively and introduced the clinical treatment. According to TCM body constitutions, it was benefit to recognize and prevent diseases through investigating the susceptible body and discussing the relation between constitutions and syndromes, and since TCM body constitutions leaded the characteristic of susceptibility and tendency of diseases and the body was stable but changed later. TCM body constitutions of 498 COPDs were diagnosed by questionnaires and the relation between the constitutions and syndromes were analyzed. The result showed that the constitutions of Qi asthenia, of phlegm-dampness and of damp-heat were common constitutions in COPDs. There was a significant correlation between TCM body constitutions and syndromes. Thus, during different period of COPD taking the treatment of adjusting the constitutions especially biased constitutions and combining "recognizing constitutions" and "recognizing syndromes" are benefit to increase the effect of prevention and treatment, and are significant to decrease the incidence and prevalence.

[Determination of vitexin-rhamnoside in Beagle dog plasma and preliminary pharmacokinetics of Yixintong sustained release tablets].

OBJECTIVE: To develop an HPLC method to determine vitexin-rhamnoside in plasma of Beagle dogs and study the pharmacokinetics and bioavailability of Yixintong sustained release tablets in Beagle dogs. METHOD: A newly-developed HPLC method using C18 column and methanol-acetonitrile-tetrahydrogenfuran-0.5% acetic acid (1:1:19.4:78.6) as mobile phase was validated, and then was employed to determine vitexin-rhamnoside in plasma of Beagle dogs after oral administration of Yixintong sustained release tablets and general tablets. The main pharmacokinetic parameters were estimated by pharmacokinetic program 3p87. The non-compartmental pharmacokinetic parameters were also calculated on basis of the statistic moment theory. RESULT: The pharmacokinetic profiles of Yixintong sustained release tablets and the general tablets were fitted to a one-and two-compartment open model, respectively. The T1/2, Tmax, AUC0-infinity and MRT for Yixintong sustained release tablets were 5.22 h, 4.0 h, 6,792.75 ng x h x mL(-1) and 8.4 h, respectively, compared with 8.94 h, 1.0 h, 5,880.4 ng x h x mL(-1) and 6.1 h for the general tablets. The relative bioavailability of the Yixintong sustained release tablets was 115.5% in Beagle dogs. CONCLUSION: The sustained-release characteristic of Yixintong sustained release tablets were confirmed by pharmacokinetic study.

[Effects of pirarubicin chemotherapy combined with hyperthermia on gastric cancer in vitro].

OBJECTIVE: To evaluate the effect of pirarubicin (THP) in combination with hyperthermia on gastric cancer tissues in vitro and explore the underlying mechanisms. METHODS: In vitro three-dimensional culture models were established with tissue biopsies from 36 patients with pathologically confirmed gastric cancer. The tumor cell viability was measured by MTS-PMS assay, and HE staining was used to study the histomorphological changes of the tissues following chemotherapy and hyperthermia. RESULTS: Synergistic tumor cell-killing effects of cisplatin, THP, and mitomycin with hyperthermia was observed in the tumor tissues (P=0.000), and THP exhibited stronger cytotoxic effects than the other drugs. Histomorphological study suggested strong killing effects of THP on the tumor tissues, which displayed disrupted tissue structure, cellular degradation and necrosis, karyopyknosis and karyolysis, with cytoplasm loss. The anti-tumor effects of THP were associated with clinical staging and pathological grading of the tumors (P=0.000), but not with the patients' gender, age, tumor size and preoperative CEA levels (P>0.05). CONCLUSION: Pirarubicin shows good synergistic effects with hyperthermia, and the cytotoxicity of pirarubicin against gastric cancer tissue is enhanced considerably by mild hyperthermia. THP can be a potential therapeutic drug for intraperitoneal chemohyperthermia.

[Research progress on oral prolonged-release preparation of traditional Chinese medicine].

This paper reviews the lastest progress on oral prolonged-release preparation of traditional Chinese medicine. Four materials, include component, effective parts, single drug, and compound drugs of traditiong Chinese medicine, have been used to produce oral prolonged-release preparation. The main contents are study of preparation and evaluation of in vitro release. There are also some research works on integrative evaluation, pharmacokinetics and pharmacological activity of the prolonged-release preparation. It believes that the study on oral prolonged-release preparation of traditional Chinese medicine will have good prospect.