Scutellaria baicalensis Georgi alleviates Clostridium difficile associated diarrhea and its modulatory effects on the gut microbiota.

The growing incidence of Clostridium difficile associated diarrhea (CDAD) underscores the urgency for potent treatments. This research delves into the therapeutic potential of Scutellaria baicalensis Georgi (Lamiaceae) root (SR) in addressing CDAD and its influence on gut microbiota. Using a CDAD mouse model and fidaxomicin as a control, SR's impact was measured through diarrhea symptoms, colonic histopathology, and C. difficile toxin levels. Employing the PacBio platform, 16S rRNA full-length gene sequencing analyzed the gut microbial composition and the effect of SR. Results revealed SR considerably alleviated diarrhea during treatment and restoration phases, with a marked decrease in colonic inflammation. C. difficile toxin levels dropped significantly with SR treatment (P < 0.001). While SR didn't augment gut microbiota's overall abundance, it enhanced its diversity. It restored levels of Proteobacteria and Bacteroidetes, reduced Akkermansia spp. and Enterococcus spp. proportions, and modulated specific bacterial species' abundance. In essence, SR effectively mitigates CDAD symptoms, curtails inflammatory reactions, and beneficially restructures gut microbiota, suggesting its potential in advanced CDAD clinical intervention.

The whitening effect of cuscutin responsible for traditional use of Bergenia purpurascens.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots and rhizomes of Bergenia purpurascens (Hook. f. et Thomson) Engl., was used as a sunscreen to protect against ultraviolet rays in Tibet of China historically, but its skin whitening constituents and pharmacological effects of this plant remained unknown. AIM OF THE STUDY: To investigate the anti-melanogenesis effect of B. purpurascens in vitro and in vivo, and then explore the preliminary mechanism. MATERIALS AND METHODS: An ultraviolet B (UVB)-induced skin injury model of mice was used to verify the ameliorative effect of B. purpurascens extract (BPE) on ultraviolet damage. Then, alpha-melanocyte stimulating hormone (α-MSH)-induced murine melanoma cell line (B16F10) melanin generation model was further adopted to approval the effects of BPE and its bioactive compound, cuscutin, in vitro. Moreover, α-MSH stimulated melanogenesis model in zebrafish was employed to confirm the anti-pigmentation effect of cuscutin. Then, proteins expressions associated with melanin production were observed using western blotting assay to explore preliminary mechanism. RESULTS: BPE inhibited UVB-induced mice injury and restored skin barrier function observably in vivo. BPE and cuscutin suppressed the overproduction of melanin in α-MSH induced B16F10 significantly, in which cuscutin exhibited better effect than well-known whitening agent α-arbutin at same 10 µg/mL concentration. Moreover, the pigmentation of zebrafish embryo was decreased by cuscutin. Finally, cuscutin showed significant downregulation of expressions of tyrosinase (TYR) and tyrosinase related protein-1 (TRP-1), TRP-2 and microphthalmia-associated transcription factor (MITF) in the melanogenic signaling pathway. CONCLUSION: B. purpurascens extract and its major bioactive constituent, cuscutin, showed potent anti-melanogenesis and skin-whitening effect by targeting TYR and TRP-2 proteins for the first time, which supported its traditional use.

Combination of dimethylmethoxy chromanol and turmeric root extract synergically attenuates ultraviolet-induced oxidative damage by increasing endogenous antioxidants in HaCaT cells.

BACKGROUND: Repeated exposure to UV generates excessive reactive oxygen species (ROS) and damages the enzymatic antioxidant defense system including quinone oxidoreductase 1 (NQO1) and superoxide dismutase (SOD) in skin. Topical application of antioxidants may prevent the undesired damage of cellular proteins, lipids and DNA in skin. Dimethylmethoxy chromanol (DMC) is a bioinspired molecule, designed to be a structural analog to the γ-tocopherol that is naturally present in vegetables and plants. Turmeric root extract (TRE) is from a plant in South Asia extensively used as a food spice & vegetable, and its main components are turmerones. As both DMC and TRE are strong antioxidants with complementary antioxidation mechanisms, the aim of this study was to investigate the enhanced protective effects of their combination on oxidative damage in HaCaT cells following UVB exposure. MATERIALS AND METHODS: The effects of single and combined administrations of DMC and TRE on the SOD activity of HaCaT cells were evaluated by the SOD assay and qPCR. The NQO1 expression in the UVB-treated HaCaT cells was analyzed by the Western Blot. Furthermore, a clinical test involving 24 subjects was conducted to evaluate the in vivo antioxidation efficacies of the serum formulated with the combination of DMC and TRE at the optimal weight ratio. RESULTS: SOD assay showed that pretreating DMC or TRE alone could not preserve the impaired HaCaT SOD activity after UVB treatment. DMC and TRE at 1:1 weight ratio was the optimal combination to enhance the HaCaT SOD activity by approximately more than 1-fold compared with either of the single treated groups. No enhancement effect was observed at other mixing ratios. The 1:1 weight ratio was further proved to be optimal as this combination boosted the NQO1 expression by more than 50%, whereas no boosting effect was observed at other mixing ratios. The clinical test of the serum containing this optimal antioxidant combination demonstrated promising in vivo antioxidation efficacies after 4-week use, including 7.16% improvement in skin lightening, 18.29% reduction in skin redness, 35.68% decrease in TEWL, 19.05% increase in skin gloss and 32.04% enhancement in skin firmness. CONCLUSION: Collectively, our results indicated that the combination of DMC and TRE at 1:1 weight ratio attenuated the UV-induced oxidative damage by synergistically boosting endogenous antioxidant enzyme activity in HaCaT cells. Therefore, this optimal antioxidant combination is a promising treatment to boost skin antioxidation defense system.

Pharmacological investigation of indole alkaloids from Alstonia scholaris against chronic glomerulonephritis.

BACKGROUND: As one of the most commonly used folk medicines in "Dai" ethno-medicine system, Alstonia scholaris (l.) R. Br. has also been used for treat "water related diseases", such as chronic kidney disease. However, few study was reported for it on the intervention of chronic glomerulonephritis (CGN). PURPOSE: To investigate the effect and potential mechanism of indole alkaloids from A. scholaris leaves in ICR mice with adriamycin nephropathy, as well as providing experimental evidence for the further application. METHODS: ICR Mice were selected for injections of adriamycin (ADR) to induce the CGN model and administered total alkaloids (TA) and four main alkaloids continuously for 42 and 28 days, respectively. The pharmacological effects were indicated by serum, urine, and renal pathological observations. The targets and pathways of indole alkaloids on CGN intervention were predicted using the network pharmacology approach, and the immortalized mice glomerular podocyte (MPC5) cells model stimulated by ADR was subsequently selected to further verify this by western blotting and RT-qPCR methods. RESULTS: TA and four major compounds dramatically reduced the levels of urinary protein, serum urea nitrogen (BUN), and creatinine (CRE) in ADR - induced CGN mice, while increasing serum albumin (ALB) and total protein (TP) levels as well as ameliorating kidney damage. Moreover, four alkaloids effected on 33 major target proteins and 153 pathways in the CGN, among which, PI3K-Akt as the main pathway, an important pathway for kidney protection by network pharmacology prediction, and then the four target proteins - HRAS, CDK2, HSP90AA1, and KDR were screened. As a result, Val-and Epi can exert a protective effect on ADR-stimulated MPC5 cells injury at a concentration of 50 µM. Furthermore, the proteins and RNA expression of HRAS, HSP90AA1, and KDR were down-regulated, and CDK2 was up-regulated after the intervention of Val-and Epi, which were supported by Western blotting and RT-qPCR. Additionally, Val-and Epi inhibited ROS production in the MPC5 cells model. CONCLUSION: This study is the first to confirm the potential therapeutic effect of alkaloids from A. scholaris on CGN. TA with major bioactive components (vallesamine and 19­epi-scholaricine) could exert protective effects against the ADR-induced CGN by regulating four key proteins: HRAS, CDK2, HSP90AA1, and KDR of the PI3K-Akt pathway.

Sinomenine Hydrochloride Can Ameliorate Benign Prostatic Hyperplasia by Lowering the 5α-Reductase 2 Level and Regulating the Balance between the Proliferation and Apoptosis of Cells.

Benign prostatic hyperplasia (BPH) is a chronic disease that affects the quality of life of older males. Sinomenine hydrochloride (SIN) is the major bioactive alkaloid isolated from the roots of the traditional Chinese medicinal plant Sinomenium acutum Rehderett Wilson. We wondered if the SIN administration exerted a regulatory effect on BPH and its potential mechanism of action. Mice with testosterone propionate-induced BPH subjected to bilateral orchiectomy were employed for in vivo experiments. A human BPH cell line (BPH-1) was employed for in vitro experiments. SIN administration inhibited the proliferation of BPH-1 cells (p < 0.05) by regulating the expression of androgen-related proteins (steroid 5-alpha reductase 2 (SRD5A2), androgen receptors, prostate-specific antigen), apoptosis-related proteins (B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)) and proliferation-related proteins (proliferating cell nuclear antigen (PCNA), mammalian target of rapamycin, inducible nitric oxide synthase) in vitro. SIN administration decreased the prostate-gland weight coefficient (p < 0.05) and improved the histological status of mice suffering from BPH. The regulatory effects of SIN administration on SRD5A2, an apoptosis-related protein (Bcl-2), and proliferation-related proteins (PCNA, matrix metalloproteinase-2) were consistent with in vitro data. SIN exerted a therapeutic effect against BPH probably related to lowering the SRD5A2 level and regulating the balance between the proliferation and apoptosis of cells. Our results provide an important theoretical basis for the development of plant medicines for BPH therapy.

Jatavaleridoids A-H, eight new iridoids from the roots and rhizomes of Valeriana jatamansi Jones.

Eight new iridoids, jatavaleridoids A-H (1-8), were isolated from the roots and rhizomes of Valeriana jatamansi. Their structures and absolute configurations were elucidated based on NMR and HRESIMS spectroscopic data, as well as quantum chemical calculation. Structurally, compounds 1-5 and 8 were rare iridoids with long-chain fatty acid esters at C-10. In addition, compound 7 showed cytotoxicity, while compounds 1 and 2 exhibited inhibition on NO production.

Cisapride versus Maren Pill for Functional Constipation: A Meta-Analysis.

Background: The efficacy and safety of cisapride in functional constipation (FC) remain unclear. This meta-analysis aimed at investigating the efficacy and safety of cisapride and Maren pill in the treatment of FC. Material and Methods. PubMed, Web of Science, Embase, Cochrane Library, WANFANG DATA, VIP, and CNKI databases were searched from inception to December 2021 for eligible comparative studies investigating the effects and safety of cisapride and Maren pill for FC. The primary outcome was the therapeutic effectiveness rate. The secondary outcomes were recurrence rate and incidence of adverse events. Results: A total of 526 studies were screened out by searching the electronic databases and by manually searching the relevant reference lists. According to the four-step process (identification, screening, eligibility, and inclusion) to select studies for meta-analysis, 521 articles were excluded. Finally, 5 studies with a total of 414 patients with FC were included in the quantitative analysis after sequential exclusion. The cisapride group had a significantly higher effectiveness rate than the control one (90.78% vs 64.97%, P < 0.05). The incidence of adverse events in the cisapride group was lower than that in the Maren pill group (10.08% vs 13.95%, P < 0.05). Similarly, the recurrence rate of the cisapride group was lower than that of the Maren pill group (32.31% vs 53.16%, P < 0.05). Conclusion: For FC patients, cisapride is more effective than Maren pill; the recurrence rate and adverse event rate are lower than the latter, which makes it a better choice. The combination of cisapride and Maren pill is a direction of future research studies, which may increase the efficiency and reduce the dosage of cisapride.

Exploring the type and strength of nonlinearity in water quality responses to nutrient loading reduction in shallow eutrophic water bodies: Insights from a large number of numerical simulations.

Reducing the load of nutrients is essential to improve water quality while water quality may not respond to the load reduction in a linear way. Despite nonlinear water quality responses being widely mentioned by studies, there is a lack of comprehensive assessment on the extent and type of nonlinear responses considering the seasonal changes. This study aimed to measure the strength of nonlinearity of theoretically possible water quality responses and explore their potential types in shallow eutrophic water bodies. Hereto, we generated 14,710 numerical water body cases that describe the water quality processes using the Environmental Fluid Dynamics Code (EFDC) and applied eight load reduction scenarios on each water body case. Inflows are simplified from Lake Dianchi. The climate conditions consider three cases: Lake Dianchi, Wissahickon Creek, and Famosa Slough. We then developed a nonlinearity strength indicator to quantify the strength and frequency of nonlinear water quality responses. Based on the quantification of nonlinearity, we clustered all the samples of water quality responses using K-Means, an unsupervised Machine Learning algorithm, to find the potential types of nonlinear water quality responses for TN (total nitrogen), TP (total phosphorus), and Chla (chlorophyll a). Results show linear or near-linear response types account for 90%, 69%, and 20% of TN, TP, and Chla samples respectively. TP and Chla could perform more types of nonlinearity. Representative nonlinear water quality responses include disproportional improvement, peak change (disappear, move forwards or afterward), and seasonal deterioration of TN after load reduction. This study would contribute to the current understanding of nonlinear water quality responses to load reduction and provide a basis to study under which conditions the nonlinear responses may emerge.

Effect of midwife intervention coupled with acupressure on the vaginal delivery rate and negative emotion in parturients with scarred uterus re-pregnancy.

OBJECTIVE: To investigate the effect of midwife intervention coupled with acupressure on the vaginal delivery rate and negative emotion in parturients with scarred uterus re-pregnancy. METHODS: A total of 85 parturients with scarred uterus re-pregnancy who agreed to trial-produce vaginally after assessment were analyzed retrospectively. Parturients were divided into the research group (43 parturients) who received midwife intervention coupled with acupressure and the control group (42 parturients) who received routine nursing intervention. The delivery mode, birth process time, postpartum hemorrhage, maternal and infant outcomes, negative emotion improvement, intrapartum pain score and family care satisfaction of parturients between the two groups were compared. RESULTS: Parturients in the research group had higher spontaneous vaginal delivery rate (67.44% vs. 45.24%, P<0.05), lower rates of lateral episiotomy, puerperal infection and neonatal asphyxia (all P<0.05), compared with the control group. No difference in vaginal midwifery rate was found (P>0.05). Shorter first stage of labor and second stage of labor (both P<0.001) and less postpartum 2 h and 24 h hemorrhage were found in the research group than in the control group (both P<0.05). After intervention, parturients in the research group versus those in the control group showed lower visual analogue scale scores in the incubation period and active period and negative emotion (Hamilton anxiety (HAMA) scale, and Hamilton depression (HAMD) scale) scores (all P<0.05) and greater nursing satisfaction (P<0.05). CONCLUSION: Midwife intervention coupled with acupressure can alleviate the degree of anxiety and depression in parturients with scarred uterus re-pregnancy, accelerate the progress of labor, relieve pain, increase spontaneous vaginal delivery rate, and improve maternal and infant outcomes.

GHRH expression plasmid improves osteoporosis and skin damage in aged mice.

The hormone secretion of GHRH-GH-IGF-1 axis in animals was decreased as aging. These hormones play an important role in maintaining bone mass and bone structure, and also affect the normal structure and function of the skin. We used plasmid-based technology to deliver growth hormone releasing hormone (GHRH) to elderly mice. In the current study, 80 and 120 µg/kg pVAX-GHRH plasmid expression plasmid were injected into old mice, the serum GHRH and insulin-like growth factor-1(IGF-1) content were increased within three weeks (P < 0.05). In the groups of 80 and 120 µg/kg plasmid, the content of procollagen type I N-terminal pro-peptide (PINP) in the serum was increased(P < 0.05), and the content of C-terminal telopeptides of type I collagen (CTX-1) in the serum was reduced significantly (P < 0.05). Furthermore, the expression of osteoprotegerin (OPG) and osteocalcin (OCN) in the femur also was increased(P < 0.05). The bone mineral density(BMD)、trabecular bone volume (BV/TV) and trabecular number(Tb.N) of mouse femur were increased significantly (P < 0.05) and trabecular separation(Tb.Sp) was decreased(P < 0.05). There were more trabecular bones in the bone marrow cavity and the trabecular bones are thicker in the groups of 80 and 120 µg/kg plasmid relative to control. The superoxide dismutase (SOD) content in the skin was increased(P < 0.05), and the malondialdehyde (MDA) content was reduced significantly (P < 0.05). Meanwhile, the skin moisture content also increased significantly(P < 0.05). Moreover, the expression of matrix metalloproteinase 3(MMP3) and matrix metalloproteinase 9(MMP9) was decreased in the skin(P < 0.05). The thickness of the dermis and epidermis of the skin had increased significantly(P < 0.05). Skin structure is more dense and complete in the two groups. These results indicate that 80 and 120 µg/kg plasmid-mediated GHRH supplementation can improve osteoporosis and skin aging in aged mice.

[Study on the Relationship between First-Time Complementary Feeding Practice and the Nutritional Status of Infants and Young Children in the Multi-Ethnic Rural Areas of Sichuan Province].

OBJECTIVE: To evaluate the current status of first food supplement and the nutrition of infants and young children in rural areas inhabited by people of Han, Tibetan, and Yi ethnicities in Sichuan Province, and to explore the relationship between the first ever feeding of food supplement and the nutritional status. METHODS: Using a multi-stage randomized cluster sampling method, we selected 2 Han counties, 2 Tibetan counties and 2 Yi counties in rural areas of Sichuan Province. These counties were previously defined as economically poor counties, but had since been lifted out of poverty. They were selected for this study before they came out of poverty. Infants and young children of 12-24 months old and their main caregivers from these counties were the subjects of the study. Structured questionnaires were used to collect information concerning the sociodemographic characteristics of infants and young children and their caregivers, and the first complementary feeding for infants and young children. Infant and young children weight scales and length/height tapes were used to collect the weight and length/height data of infants and young children. Unconditional logistic regression was used to analyze the correlation between the behavior of giving supplementary food for the first time to infants and young children and their nutritional status. RESULTS: A total of 1117 pairs of infants and children and their caregivers were investigated. Regarding the time of first supplementary food addition, nearly half of the caregivers in Han areas started adding supplementary food when the infants were 6 months old, accounting for 43.07% (171/397). Most of the caregivers in Yi and Tibetan areas started giving infants and young children supplementary food when they were less than 6 months old, accounting for 77.18% (301/390) and 47.58% (157/330), respectively. In terms of the types of supplementary food added for the first time, caregivers in Han areas mainly used homemade rice cereal, accounting for 41.56% (165/397), caregivers in Tibetan areas mainly used meat, vegetables or fruits and other complementary foods, accounting for 42.12% (139/330), and caregivers in Yi areas mainly used homemade rice cereal, accounting for 46.41% (181/390). The overall malnutrition rate of infants and young children was 28.83% (322/1117) and the malnutrition rate of infants and young children in Han, Tibetan, and Yi areas were 10.58% (42/397), 24.85 (82/330), and 50.77 (198/390), respectively. The regression analysis results show that after controlling for confounding factors, compared with Han areas, it is more likely for infants and young children in Yi areas to be malnourished ( OR=9.49, 95% CI 6.00-15.00). Compared with adding other types of complementary foods for the first time, infants and young children given iron-fortified rice cereal had a lower risk of malnutrition ( OR=0.54, 95% CI0.29-0.99). CONCLUSION: The multi-ethnic rural areas of Sichuan Province had problems that supplementary foods are added too early, and that the types of supplementary foods added for the first time were not appropriate. In addition, the nutritional status of local infants and young children in these areas was causing concerns. The malnutrition problem of infants and young children was especially prominent in the Yi ethnic areas. Adding iron-fortified rice cereal for the first time could reduce the possibility of malnutrition in infants and young children to a certain extent. It is recommended that attention should be given to the health education intervention of the first supplementary food for infants and young children to effectively improve the nutritional status of infants and young children in these areas.

[Application of oscillating chemical fingerprint technology combined with mathematical analysis method in quality control analysis of traditional Chinese medicine and food].

Oscillating chemical fingerprint is a nonlinear dynamic fingerprint technology that reflects the overall redox activity of the entire system based on potential-time changes in multi-stage chemical reactions. This article summarizes the application of oscillating chemical fingerprint technology combined with mathematical analysis method in the qualitative and quantitative analysis of traditional Chinese medicine and food in recent years, including similarity analysis, principal component analysis, cluster analysis and other qua-litative analysis methods, as well as linear, logarithmic, exponential, polynomial, multivariate analysis and other quantitative analysis methods, so as to provide meaningful information for further quality control analysis of the oscillation chemical fingerprint technology in the field of traditional Chinese medicine and food.

Interplay between male reproductive system dysfunction and the therapeutic effect of flavonoids.

Male infertility has affected many families around the world. However, due to the mechanism underlying male reproductive system dysfunction are not completely elucidated, the use of drugs for male reproductive system dysfunction treatment only insignificant higher pregnancy outcomes, low-quality evidence suggests that clinical pregnancy rates may increase. Therefore, the focus in the future will be on developing more viable treatment options to prevent or treatment of male reproductive system dysfunction and achieve the purpose of improving fertility. Interestingly, natural products, as the potential inhibitors for the treatment of male reproductive system dysfunction, have shown a good therapeutic effect. Among many natural products, flavonoids have been extensively investigated for the treatment of male reproductive system dysfunction, such as testicular structural disruption, spermatogenesis disturbance and sperm quality decline. Flavonoids have been reported to have antioxidant, anti-inflammatory, immune stimulating, anti-apoptotic, anticarcinogenic, anti-allergic and antiviral activities, investigating for the treatment of male reproductive system dysfunction. In this review, we evaluate the therapeutic effects of flavonoids on male reproductive system dysfunction under different cellular scenarios and summarize the therapeutic strategies of flavonoids based on the aforementioned retrospective analysis. In the end, we describe some perspective research areas relevant to the application of flavonoids in the treatment of male reproductive system dysfunction.

[Qualitative and quantitative analysis of Rhodobryum giganteum by using nonlinear oscillating chemical fingerprint technique].

A new method for qualitative and quantitative analysis of Rhodobryum giganteum by using the nonlinear oscillating chemical was established for improving the quality control standard of R. giganteum. Its potential(E)/time(t) curve was recorded by electrochemical workstation in the oscillation reaction system of BrO~-_3-Ce(SO_4)_2-H_2SO_4-malonic acid/tartaric acid. The nonlinear oscillating chemical fingerprints were investigated for repeatability, and it was found that the RSD values of the four characteristic parameters of R. giganteum were less than 4.1%, indicating a good repeatability and high precision of this experiment. After optimizing the experimental parameters such as particle size, rotation speed and temperature, a new method based on nonlinear oscillating chemical was used for qualitative and quantitative analysis of R. giganteum. The results showed that there was a good linear relationship between the induction time/the period of oscillation and the dosage of herbs(0.1-1.1 g), with the relative coefficients of 0.978 and 0.975, respectively. Besides, the highest potential showed a nonlinear relationship with the dosage of herbs, with the relative coefficient of 0.999. This method was also used to discriminate the R. giganteum and R. roseum. They were similar in appearance, but their fingerprints were quite different. Independent sample t test results showed that there were significant differences in the oscillation time, the maximum amplitude and the induction time, providing a basis for the identification of the basic sources of Herba Rhodobryi Rasei.

Magnetic effervescent tablet-assisted ionic liquid dispersive liquid-liquid microextraction of selenium for speciation in foods and beverages.

A novel, simple and rapid method based on magnetic effervescent tablet-assisted ionic liquid dispersive liquid-liquid microextraction (MEA-IL-DLLME) followed by graphite furnace atomic absorption spectrometry (GFAAS) determination was established for the speciation of selenium in various food and beverage samples. In the procedure, a special magnetic effervescent tablet containing CO2 sources (sodium carbonate and sodium dihydrogenphosphate), ionic liquids and Fe3O4 magnetic nanoparticles (MNPs) was used to combine extractant dispersion and magnetic recovery procedures into a single step. The parameters influencing the microextraction efficiency, such as pH of the sample solution, volume of ionic liquid, amount of MNPs, concentration of the chelating agent, salt effect and matrix effect were investigated and optimised. Under the optimised conditions, the limits of detection (LODs) for Se(IV) were 0.021 µg l(-)(1) and the linear dynamic range was 0.05-5.0 µg l(-)(1). The relative standard deviation for seven replicate measurements of 1.0 µg l(-)(1) of Se(IV) was 2.9%. The accuracy of the developed method was evaluated by analysis of the standard reference materials (GBW10016 tea, GBW10017 milk powder, GBW10043 Liaoning rice, GBW10046 Henan wheat, GBW10048 celery). The proposed method was successfully applied to food and beverage samples including black tea, milk powder, mushroom, soybean, bamboo shoots, energy drink, bottled water, carbonated drink and mineral water for the speciation of Se(IV) and Se(VI) with satisfactory relative recoveries (92.0-108.1%).

Endocrine Disruption throughout the Hypothalamus-Pituitary-Gonadal-Liver (HPGL) Axis in Marine Medaka (Oryzias melastigma) Chronically Exposed to the Antifouling and Chemopreventive Agent, 3,3'-Diindolylmethane (DIM).

Despite being proposed as a promising antifouling and chemopreventive agent, the environmental risks of 3,3'-diindolylmethane (DIM) are scarcely investigated. Therefore, this study used adult marine medaka (Oryzias melastigma) as a model organism to examine the toxicological effects and underlying mechanism of DIM throughout the hypothalamus-pituitary-gonadal-liver (HPGL) axis following 28 days of exposure to low DIM concentrations (0 and 8.46 µg/L). The results showed that altered gene transcription in the hypothalamus, pituitary, and gonads contributed to the great imbalance in hormone homeostasis. The lowered estradiol (E2)/testosterone (T) and E2/11-keto-testosterone (11-KT) ratios in female plasma resulted in decreased synthesis and levels of vitellogenin (VTG) and choriogenin in the liver and plasma, and vice versa in males. Subsequently, VTG and choriogenin deficiency blocked the reproductive function of the ovary as indicated by decreased fecundity and offspring viability, whereas in male medaka, DIM mainly targeted the liver and induced severe vacuolization. Proteomic profiling of plasma revealed that the sex-specific susceptibility to DIM could be attributed to the increased detoxification and oxidative defense in males. Overall, this study identified the endocrine disruption and reproductive impairment potency of DIM and first elucidated its mechanisms of action in medaka. The differential responses to DIM (estrogenic activities in the male but antiestrogenic activities in the female) provided sensitive biomarkers characteristic of each sex. Considering the chemical stability and potent endocrine disturbance at low concentration, the application of DIM either as an antifouling or chemopreventive agent should be approached with caution in marine environments.

Chronic Exposure of Marine Medaka (Oryzias melastigma) to 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) Reveals Its Mechanism of Action in Endocrine Disruption via the Hypothalamus-Pituitary-Gonadal-Liver (HPGL) Axis.

In this study, marine medaka (Oryzias melastigma) were chronically exposed for 28 days to environmentally realistic concentrations of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) (0, 0.76, 2.45, and 9.86 µg/L), the active ingredient in commercial antifouling agent SeaNine 211. Alterations of the hypothalamus-pituitary-gonadal-liver (HPGL) axis were investigated across diverse levels of biological organization to reveal the underlying mechanisms of its endocrine disruptive effects. Gene transcription analysis showed that DCOIT had positive regulatory effects mainly in male HPGL axis with lesser extent in females. The stimulated steroidogenic activities resulted in increased concentrations of steroid hormones, including estradiol (E2), testosterone (T), and 11-KT-testosterone (11-KT), in the plasma of both sexes, leading to an imbalance in hormone homeostasis and increased E2/T ratio. The relatively estrogenic intracellular environment in both sexes induced the hepatic synthesis and increased the liver and plasma content of vitellogenin (VTG) or choriogenin. Furthermore, parental exposure to DCOIT transgenerationally impaired the viability of offspring, as supported by a decrease in hatching and swimming activity. Overall, the present results elucidated the estrogenic mechanisms along HPGL axis for the endocrine disruptive effects of DCOIT. The reproductive impairments of DCOIT at environmentally realistic concentrations highlights the need for more comprehensive investigations of its potential ecological risks.

Application of the QUAL2K model to design an ecological purification scheme for treated effluent of a wastewater treatment plant.

Treated effluent from wastewater treatment plants has become an important source of excess nutrients causing eutrophication in water. In this study, an ecological purification method was used to further treat eutrophic water. A three-season ecological purification scheme which comprised an emergent plant (Eme.), a submerged plant (Sub.) and a novel biological rope (Bio.), was designed for the treated effluent canal of a wastewater treatment plant. The removal parameters determined from the experiment were input into a QUAL2K model to simulate downstream water quality of the treated effluent canal. Respective removal rates of total nitrogen and total phosphorus of the Eme., Sub. and Bio. were 32.48-37.33% and 31.63-39.86% in summer, 14.12-33.61% and 17.74-23.80% in autumn, and 14.13-18.03% and 10.05-12.75% in winter, with 1-day reaction time. Optimal combinations for summer, autumn/spring, and winter are Eme. + Bio., Eme. + Bio. + Sub., and Sub. + Bio., respectively. Simulated load reduction rates of total nitrogen and total phosphorus for the treated effluent canal were 42.64-78.40% and 30.98-78.29%, respectively, year round with 2.5-day reaction time. This study provides an efficient evaluation and design method for ecological purification engineering.

Calculation of permissible load capacity and establishment of total amount control in the Wujin River Catchment--a tributary of Taihu Lake, China.

The deterioration of water quality in Taihu Lake, China, has caused widespread concern in recent years. The primary pollution sources of Taihu Lake are its inflow rivers. Effective environmental water management strategies need to be implemented in these rivers to improve the water quality of Taihu Lake and to promote sustainable development in the region. In this study, the QUAL2K model is used in conjunction with the trial and error approach to assess permissible load capacities for the Wujin River (a major tributary of Taihu Lake) in terms of COD, NH3-N, TN, and TP. Results show that permissible annual loads for these pollutants are 5216.31, 491.71, 948.53, and 104.38 t, respectively. This suggests that COD, NH3-N, TN, and TP loads in the Wujin River catchment need to be reduced by 13.35, 27.26, 47.75, and 37.08 %, respectively, to satisfy national water quality objectives. Total amount control measures are proposed to control and reduce pollution loads of the Wujin River catchment. The method applied in this study should provide a sound basis for water environmental management decision-making.

Circadian clock, cancer, and chemotherapy.

The circadian clock is a global regulatory system that interfaces with most other regulatory systems and pathways in mammalian organisms. Investigations of the circadian clock-DNA damage response connections have revealed that nucleotide excision repair, DNA damage checkpoints, and apoptosis are appreciably influenced by the clock. Although several epidemiological studies in humans and a limited number of genetic studies in mouse model systems have indicated that clock disruption may predispose mammals to cancer, well-controlled genetic studies in mice have not supported the commonly held view that circadian clock disruption is a cancer risk factor. In fact, in the appropriate genetic background, clock disruption may instead aid in cancer regression by promoting intrinsic and extrinsic apoptosis. Finally, the clock may affect the efficacy of cancer treatment (chronochemotherapy) by modulating the pharmacokinetics and pharmacodynamics of chemotherapeutic drugs as well as the activity of the DNA repair enzymes that repair the DNA damage caused by anticancer drugs.