Family-based Helicobacter pylori infection control and management strategy and screen-and-treat strategy are highly cost-effective in preventing multiple upper gastrointestinal diseases in Chinese population at national level.

BACKGROUND: The overall benefits of the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management (FBCM) and screen-and-treat strategies in preventing multiple upper gastrointestinal diseases at national level in China have not been explored. We investigate the cost-effectiveness of these strategies in the whole Chinese population. MATERIALS AND METHODS: Decision trees and Markov models of H. pylori infection-related non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were developed to simulate the cost-effectiveness of these strategies in the whole 494 million households in China. The main outcomes include cost-effectiveness, life years (LY), quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). RESULTS: When compared with no-screen strategy, both FBCM and screen-and-treat strategies reduced the number of new cases of NUD, PUD, PUD-related deaths, and the prevalence of GC, and cancer-related deaths. The costs saved by these two strategies were $1467 million and $879 million, quality-adjusted life years gained were 227 million and 267 million, and life years gained were 59 million and 69 million, respectively. Cost-effectiveness analysis showed that FBCM strategy costs -$6.46/QALY and -$24.75/LY, and screen-and-treat strategy costs -$3.3/QALY and -$12.71/LY when compared with no-screen strategy. Compared to the FBCM strategy, the screen-and-treat strategy reduced the incidence of H. pylori-related diseases, added 40 million QALYs, and saved 10 million LYs, but at the increased cost of $588 million. Cost-effectiveness analysis showed that screen-and-treat strategy costs $14.88/QALY and $59.5/LY when compared with FBCM strategy. The robustness of the results was also verified. CONCLUSIONS: Both FBCM and screen-and-treat strategies are highly cost-effective in preventing NUD, PUD, and GC than the no-screen strategy in Chinese families at national level. As FBCM strategy is more practical and efficient, it is expected to play a more important role in preventing familial H. pylori infection and also serves as an excellent reference for other highly infected societies.

Which Drugs are More Effective in Preventing Familial Adenomatous Polyposis Progression Based on Network Meta-Analysis?

BACKGROUND: Familial adenomatous polyposis (FAP) is an inherited disorder. At present, an increasing number of medications are being employed to treat FAP; however, only a few have been assessed for their efficacy and safety. Therefore, this study aimed to conduct a network meta-analysis to compare the therapeutic outcomes and adverse drug reactions of all FAP-associated medications. METHOD: Six relevant databases were searched to identify pertinent randomized controlled trials (RCTs), and information on the dosage and frequency of various drugs was extracted. Additionally, data on changes in polyp counts and dimensions, as well as treatment-related adverse reactions for different medications were collected. The Bayesian method was employed to directly or indirectly compare the impact of different treatment regimens on changes in polyp numbers and diameters, and the safety of the drugs was investigated. RESULTS: CXB at 16 mg/kg/day significantly reduced polyp numbers. Celecoxib at 8 mg/kg/day and sulindac (150 mg twice daily) plus erlotinib (75 mg/day) were effective for tolerant FAP patients. Additionally, EPAFFA 2 g daily and sulindac (150 mg twice daily) plus erlotinib (75 mg/day) emerged as the most effective for reducing polyp size. CONCLUSION: The most effective treatment for reducing the number of colorectal polyps is celecoxib 16 mg/kg/day. On the other hand, a daily dosage of 2 g EPA-FFA demonstrates the best results in terms of decreasing colorectal polyp diameter.

Interaction of 17α-ethinylestradiol and methyltestosterone in western mosquitofish (Gambusia affinis) across two generations.

The interactions between estrogen and androgen in aquatic animals remain largely unknown. In this study, two generations (F0 and F1) of western mosquitofish (Gambusia affinis) were continuously exposed to 17α-ethinylestradiol (EE2, 10 ng/L), methyltestosterone (MT, 10 ng/L (MTL); 50 ng/L (MTH)), and mixtures (EE2+MTL and EE2+MTH). Various endpoints, including sex ratio (phenotypic and genetic), secondary sex characteristics, gonadal histology, and transcriptional profile of genes, were examined. The results showed that G. affinis exposed to MTH and EE2+MTH had a > 89.7 % of phenotypic males in F1 generation, with 34.5 and 50.0 % of these males originated from genetic females, respectively. Moreover, females from F0 and F1 generations exposed to MTH and EE2+MTH exhibited masculinized anal fins and skeletons. The combined effect of MT and EE2 on most endpoints was dependent on MT. Furthermore, significant transcriptional alterations in certain target genes were observed in both the F0 and F1 generations by EE2 and MT alone and by mixtures, showing some degree of interactions. These findings that the effects of EE2+MTH were primarily on the phenotypic sex of G. affinis in offspring generation suggest that G. affinis under chronic exposure to the binary mixture contaminated water could have sex-biased populations.

An azole fungicide climbazole damages the gut-brain axis in the grass carp.

Azole antifungal climbazole has frequently been detected in aquatic environments and shows various effects in fish. However, the underlying mechanism of toxicity through the gut-brain axis of climbazole is unclear. Here, we investigated the effects of climbazole at environmental concentrations on the microbiota-intestine-brain axis in grass carp via histopathological observation, gene expression and biochemical analyses, and high-throughput sequencing of the 16 S rRNA. Results showed that exposure to 0.2 to 20 µg/L climbazole for 42 days significantly disrupted gut microbiota and caused brain neurotoxicity in grass carp. In this study, there was an alteration in the phylum and genus compositions in the gut microbiota following climbazole treatment, including reducing Fusobacteria (e.g., Cetobacterium) and increasing Actinobacteria (e.g., Nocardia). Climbazole disrupted intestinal microbial abundance, leading to increased levels of lipopolysaccharide and tumor necrosis factor-alpha in the gut, serum, and brain. They passed through the impaired intestinal barrier into the circulation and caused the destruction of the blood-brain barrier through the gut-brain axis, allowing them into the brain. In the brain, climbazole activated the nuclear factor kappaB pathway to increase inflammation, and suppressed the E2-related factor 2 pathway to produce oxidative damage, resulting in apoptosis, which promoted neuroinflammation and neuronal death. Besides, our results suggested that this neurotoxicity was caused by the breakdown of the microbiota-gut-brain axis, mediated by reduced concentrations of dopamine, short chain fatty acids, and intestinal microbial activity induced by climbazole.

ABTB1 facilitates the replication of influenza A virus by counteracting TRIM4-mediated degradation of viral NP protein.

Influenza A viruses (IAVs) continue to cause tremendous economic losses to the global animal industry and respiratory diseases and deaths among humans. The nuclear import of the vRNP complex, composed of polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), polymerase acidic protein (PA), nucleoprotein (NP), and viral RNA, is essential for the efficient replication of IAV. Host factors involved in this process can be targeted for the development of countermeasures against IAV infection. Here, we found that Ankyrin Repeat and BTB Domain Containing 1 (ABTB1) promotes the replication of IAV, and positively regulates the nuclear import of the vRNP complex. ABTB1 did not interact directly with NP, indicating that ABTB1 plays an indirect role in facilitating the nuclear import of the vRNP complex. Immunoprecipitation and mass spectrometry revealed that Tripartite Motif Containing 4 (TRIM4) interacts with ABTB1. We found that TRIM4 relies on its E3 ubiquitin ligase activity to inhibit the replication of IAV by targeting and degrading NP within the incoming vRNP complex as well as the newly synthesized NP. ABTB1 interacted with TRIM4, leading to TRIM4 degradation through the proteasome system. Notably, ABTB1-mediated degradation of TRIM4 blocked the effect of TRIM4 on NP stability, and largely counteracted the inhibitory effect of TRIM4 on IAV replication. Our findings define a novel role for ABTB1 in aiding the nuclear import of the vRNP complex of IAV by counteracting the destabilizing effect of TRIM4 on the viral NP protein.

Association between small nucleolar RNA host gene expression and survival outcome of colorectal cancer patients: A meta-analysis based on PRISMA and bioinformatics analysis.

Introduction: Growing evidence shows that long non-coding RNA small nucleolar RNA host genes (lncRNA SNHGs) enact an pivotal regulatory roles in the shorter survival outcome of colorectal cancer (CRC). However, no research has systematically evaluated the correlation among lncRNA SNHGs expression and survival outcome of CRC. This research indented to screen whether exist potential prognostic effect of lncRNA SNHGs in CRC patientss using comprehensive review and meta-analysis. Methods: Systematic searches were performed from the six relevant databases from inception to October 20, 2022. The quality of published papers was evaluated in details. We pooled the hazard ratios (HR) with 95% confidence interval (CI) through direct or indirect collection of effect sizes, and odds ratios (OR) with 95% CI by collecting effect sizes within articles. Detailed downstream signaling pathways of lncRNA SNHGs were summarized in detail. Results: 25 eligible publications including 2,342 patients were finally included to appraise the association of lncRNA SNHGs with prognosis of CRC. Elevated lncRNA SNHGs expression was revealed in colorectal tumor tissues. High lncSNHG expression means bad survival prognosis in CRC patients (HR=1.635, 95% CI: 1.405-1.864, P<0.001). Additionally, high lncRNA SNHGs expression was inclined to later TNM stage (OR=1.635, 95% CI: 1.405-1.864, P<0.001), distant lymph node invasion, distant organ metastasis, larger tumor diameter and poor pathological grade. Begg's funnel plot test using the Stata 12.0 software suggested that no significant heterogeneity was found. Conclusion: Elevated lncRNA SNHGs expression was revealed to be positively correlated to discontented CRC clinical outcome and lncRNA SNHG may act as a potential clinical prognostic index for CRC patients.

Characterization of immune landscape and development of a novel N7-methylguanine-related gene signature to aid therapy in recurrent aphthous stomatitis.

OBJECTIVES: Recurrent aphthous stomatitis (RAS) is the most common inflammatory disease of the oral mucosa resulting in an impaired life quality and even leading to tumors in susceptible populations. N7-Methylguanine (m7G) plays a vital role in various cellular activities but has not yet been investigated in RAS. We aimed at picturing the immune landscape and constructing an m7G-related gene signature, and investigating candidate drugs and gene-disease association to aid therapy for RAS. METHODS: For our study, m7G-related differentially expressed genes (DEGs) were screened. We outlined the immune microenvironment and studied the correlations between the m7G-related DEGs and immune cells/pathways. We performed functional enrichment analyses and constructed the protein-protein interaction (PPI) and multifactor regulatory network in RAS. The m7G-related hub genes were extracted to formulate the corresponding m7G predictive signature. RESULTS: We obtained 11 m7G-related DEGs and studied a comprehensive immune infiltration landscape, which indicated several immune markers as possible immunotherapeutic targets. The PPI and multifactor regulatory network was constructed and 4 hub genes (DDX58, IFI27, IFIT5, and PML) were identified, followed by validation of the corresponding m7G predictive signature for RAS. GO and KEGG analyses revealed the participation of JAK-STAT and several immune-related pathways. Finally, we suggested candidate drugs and gene-disease associations for potential RAS medical interventions. CONCLUSIONS: The present study pictured a comprehensive immune infiltration landscape and suggested that m7G played a vital role in RAS through immune-related pathways. This study provided new insight for the future investigation of the mechanisms and therapeutic strategies for RAS.

Photodynamic Inactivation of Bacteria and Biofilms with Benzoselenadiazole-Doped Metal-Organic Frameworks.

Bacterial biofilms are difficult to treat due to their resistance to traditional antibiotics. Although photodynamic therapy (PDT) has made significant progress in biomedical applications, most photosensitizers have poor water solubility and can thus aggregate in hydrophilic environments, leading to the quenching of photosensitizing activity in PDT. Herein, a benzoselenadiazole-containing ligand was designed and synthesized to construct the zirconium (IV)-based benzoselenadiazole-doped metal-organic framework (Se-MOF). Characterizations revealed that Se-MOF is a type of UiO-68 topological framework with regular crystallinity and high porosity. Compared to the MOF without benzoselenadiazole, Se-MOF exhibited a higher 1O2 generation efficacy and could effectively kill Staphylococcus aureus bacteria under visible-light irradiation. Importantly, in vitro biofilm experiments confirmed that Se-MOF could efficiently inhibit the formation of bacteria biofilms upon visible-light exposure. This study provides a promising strategy for developing MOF-based PDT agents, facilitating their transformation into clinical photodynamic antibacterial applications.

Characterization of the chemical constituents and metabolic profile of Polygonum cuspidatum Sieb. et Zucc. in rat plasma, urine, and feces by ultra-high performance liquid chromatography coupled with Quadrupole-Exactive Orbitrap mass spectrometry.

Polygonum cuspidatum Sieb. et Zucc. is a traditional and popular Chinese medicine with a wide spectrum of pharmacological effects such as anti-bacterial, anti-inflammatory, and anti-tumor activities together with other health effects like lowering lipids, preventing diabetes, and regulating the immune system. It is of great significance to explore the complex chemical constituents and metabolic process of Polygonum cuspidatum in vivo to further clarify the effective substances. However, studies on its metabolism in vivo were not comprehensive in previous literature. In this study, ultra-high performance liquid chromatography coupled with Quadrupole-Exactive Orbitrap mass spectrometry was used to comprehensively identify the chemical constituents in Polygonum cuspidatum and further analyze its metabolic profile in rats. Compared with reference substances, various databases, and literature retrieval, 62 compounds were inferred from the Polygonum cuspidatum extract. Furthermore, a total of 119 compounds, including 44 prototype compounds and 75 metabolites, were annotated in rat plasma, urine, and feces. The main metabolic pathways of Polygonum cuspidatum in rats included hydrogenation reduction, hydroxylation, dehydration, methylation, sulfation, and glucuronidation. This is the first systematic study on the chemical constituents of Polygonum cuspidatum and its metabolic profile in vivo, which contributes to finding its bioactive components and seeking its therapeutic targets.

Pre-expanded muscle-sparing Latissimus Dorsi free flap: An ideal option for the reconstruction of extensive anterior knee contractures.

BACKGROUND: Extensive and complex contractures in the anterior knee area can pose a significant challenge for reconstruction due to insufficient skin and soft tissue coverage and poor cosmetic and functional outcomes using traditional methods. We presented our experience with pre-expanded muscle-sparing latissimus dorsi (LD) free flap as an alternative option for large-scale anterior knee reconstruction. METHODS: From January 2016 to December 2020, we applied this surgical technique in six patients with large postburn or post-traumatic contractures of the anterior knee. After tissue expansion of several months, the expanded muscle-sparing LD free flap was harvested and transferred to resurface the lesions. Operative procedures, postoperative complications, and long-term outcomes were evaluated. RESULTS: A total of six patients aged 7 to 32 years (mean: 20 years) were reconstructed successfully without any major complication. The flap ranged from 20 × 8 cm to 40 × 16 cm. All donor sites were primarily closed. Follow-up (range: 12 to 24 months) evaluation showed satisfactory results in both cosmetic and functional aspects. CONCLUSIONS: Pre-expanded muscle-sparing LD free flap is a reliable and effective choice for extensive anterior knee contracture reconstruction with satisfactory esthetic and functional outcome. It can provide substantial amount of soft tissue coverage with minimal complications and donor-site morbidity. Furthermore, it offers a good basis for next-step orthopedic surgery, such as total knee arthroplasty (TKA).

Influenza A virus use of BinCARD1 to facilitate the binding of viral NP to importin α7 is counteracted by TBK1-p62 axis-mediated autophagy.

As a major component of the viral ribonucleoprotein (vRNP) complex in influenza A virus (IAV), nucleoprotein (NP) interacts with isoforms of importin α family members, leading to the import of itself  and vRNP complex into the nucleus, a process pivotal in the replication cycle of IAV. In this study, we found that BinCARD1, an isoform of Bcl10-interacting protein with CARD (BinCARD), was leveraged by IAV for efficient viral replication. BinCARD1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex activity. Moreover, we found that BinCARD1 interacted with NP to promote NP binding to importin α7, an adaptor in the host nuclear import pathway. However, we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3, and that TBK1 appeared to degrade BinCARD1. We showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage, which was recognized by the TBK1-p62 axis for autophagic degradation. Overall, our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication, and two mechanisms in the host defense system are triggered-innate immune signaling and autophagic degradation-to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.

Systematic Identification, Fragmentation Pattern, And Metabolic Pathways of Hyperoside in Rat Plasma, Urine, And Feces by UPLC-Q-Exactive Orbitrap MS.

Hyperoside is a natural flavonol glycoside, which has antioxidation, antitumor, and anticancer activities together with other healthy effects like improving cardiovascular function, protecting the liver, and regulating the immune system. It is a popular compound used in the traditional Chinese medicine and different studies on hyperoside are present in the literature. However, studies on the metabolism of hyperoside in vivo were not comprehensive. In this study, UPLC-Q-Exactive Orbitrap MS technology was used to establish a rapid and comprehensive analysis strategy to explore the metabolites and metabolic process of hyperoside in rats. The metabolites of hyperoside were systematically identified in rat plasma, urine, and feces. According to the hyperoside standard substance and relevant works of literature, a total of 33 metabolites were identified, including 16 in plasma, 31 in urine, and 14 in feces. Among them, the metabolites quercetin and dihydroquercetin were unambiguously confirmed by comparison with standard substances. In addition, 13 metabolites had not been reported in hyperoside metabolism-related articles at present. The metabolic reactions of hyperoside in vivo were further explored, including phase I metabolism (hydroxylation, dehydroxylation, glycoside hydrolysis, hydrogenation, and hydration) and phase II metabolism (methylation, acetylation, sulfation, and glucuronide conjugation). The fragment ions of hyperoside and its metabolites were usually produced by glucoside bond hydrolysis, the neutral loss of (CO + OH), COH, CO, O, and Retro-Diels Alder (RDA) cleavage. In conclusion, this study comprehensively characterized the metabolism of hyperoside in rats, providing a basis for exploring its various biological activities.

Transgenerational effects of androstadienedione and androstenedione at environmentally relevant concentrations in zebrafish (Danio rerio).

Androgens androstadienedione (ADD) and androstenedione (AED) are predominant steroid hormones in surface water, and can disrupt the endocrine system in fish. However, little is known about the transgenerational effects of ADD and AED in fish. In the present study, F0 generation was exposed to ADD and AED from 21 to 144 days post-fertilization (dpf) at nominal concentrations of 5 (L), 50 (M) and 500 (H) ng L-1, and F1 generation was domesticated in clear water for 144 dpf. The sex ratio, histology and transcription in F0 and F1 generations were examined. In the F0 generation, ADD and AED tended to be estrogenic in zebrafish, resulting in female biased zebrafish populations. In the F1 generation, ADD at the H level caused 63.5% females, while AED at the H level resulted in 78.7% males. In brain, ADD and AED had similar effects on circadian rhythm in the F0 and F1 generations. In the F1 eleutheroembryos, transcriptomic analysis indicated that neuromast hair cell related biological processes (BPs) were overlapped in the ADD and AED groups. Taken together, ADD and AED at environmentally relevant concentrations had transgenerational effects on sex differentiation and transcription in zebrafish.

Cyclophosphamide affects eye development and locomotion in zebrafish (Danio rerio).

Cyclophosphamide (CP) is a broad-spectrum anticancer drug and has been frequently detected in aquatic environments due to its incomplete removal by wastewater treatment facilities and slow degradation in waters. Its toxicity in fish remains largely unknown. In this study, zebrafish eggs <4 h post fertilization (hpf) were exposed to CP at the concentrations from 0.5 to 50.0 µg/L until 168 hpf, and its toxicity was evaluated by biochemical, transcriptomic, and behavioral approaches. The results showed that malformation and mortality rates increased with CP concentrations. The 7-day malformation EC50 and mortality (LC30) by CP were calculated to be 86.8 µg/L and 7.5 mg/L, respectively. Inhibited startle response (light to dark) (a minimal of 19%) and reduced swimming velocity (a minimal of 30%) were observed in the CP-exposed larvae. The thicknesses of retinal ganglion layer, inner plexiform layer, and inner nuclear layer in the retina were increased after exposure to CP. Meanwhile, exposure to CP increased karyorrhexis and karyolysis in the liver tissue. Transcriptomic analysis identified 607 differentially expressed genes (DEGs) (159 up-regulated and 448 down-regulated). A significant reduction in the transcripts of sgk1 (the FoxO pathway), jun (the MAPK pathway), and diabloa (apoptosis pathway) were observed in the CP-treated larvae. This study has demonstrated that low concentrations of CP cause malformation, reduced swimming capacity, histopathological alterations in the retina and liver tissues, and interference on transcriptional expressions of key genes associated with different pathways. The ecological risk of CP and other anticancer drugs to aquatic organisms merits future investigation.

Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat.

BACKGROUND: Plantaginis Semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but its pharmacological mechanism remains unclear. This study investigated the therapeutic mechanism of Plantaginis Semen extract on potassium oxonate -induced HUA rats based on a lipidomics approach. METHODS: A model of HUA was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis Semen groups (n = 7). The Plantaginis Semen groups were treated orally with Plantaginis Semen, 0.9375, 1.875  or 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were  measured using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used for the serum lipidomics analysis, multivariate statistical analysis and independent samples t-test were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors were determined by quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: Compared with the model group, the levels of serum UA, Cr, TG and TNF-α were significantly (p < 0.05) decreased in benzbromarone and three Plantaginis Semen groups. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was  most affected. These perturbations  were partially restored via treatment of benzbromarone and Plantaginis Semen. Additionally, the mRNA expression levels of urate anion transporter 1 (URAT1) and phosphatidylinositol 3-kinase/protein kinases B (PI3K/Akt) were significantly decreased (p < 0.01) after treatment with benzbromarone and high dose of Plantaginis Semen. CONCLUSIONS: Plantaginis Semen had significant effects on anti-HUA, anti-inflammatory and renal protection. It attenuated potassium oxonate-induced HUA through regulation of lipid metabolism disorder.

Divergent effects of hydrological alteration and nutrient addition on greenhouse gas emissions in the water level fluctuation zone of the Three Gorges Reservoir, China.

Changes in global rainfall patterns and construction of artificial dams have led to widespread alteration of hydrological processes in riparian ecosystems. At the same time, many riparian ecosystems, such as those associated with the Yangtze, are being subjected to enhanced inputs of nitrogen (N) and phosphorus (P) due to intensified agricultural activity in surrounding uplands. Together, these environmental changes may alter the magnitude and direction of greenhouse gasses (GHGs) fluxes from riparian soils. We conducted an in situ experiment combined with quantitative PCR approach (qPCR) to elucidate the effects of hydrological alterations (continuous flooding (CF), periodic flooding (PF), and no flooding (NF)) and nutrient addition (N addition (urea, 100 kg N ha-1 y-1), P addition (P2O5, 20 kg ha-1y-1), N + P addition, and control (CK)) on three major GHGs including carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) fluxes as well as the underlying mechanisms. Our results showed that hydrological alterations greatly affected GHGs emissions, possibly by altering soil moisture, soil organic C, and C:N ratios. The CF, with higher soil moisture and lower C:N ratio, increased CH4 emissions 13-fold and reduced CO2 and N2O emissions by 37.3% and 72.2% averaged over the growing seasons compared with no flooding. PF enhanced CH4 emissions 5.7-fold and decreased N2O emissions by 69.0% in comparison with no flooding. Nutrient additions had no significant effect on CO2 or CH4 flux, but P addition significantly lowered N2O flux. Interactions between hydrological alterations and nutrient additions were not detected for any GHGs. As a result, hydrological alterations and nutrient additions affected the global warming potential (GWP) of growing season GHG budgets on a 100-year time horizon, mainly by changing the CO2 emissions. CF reduced GWP from 597 to 439 g CO2-eq m-2, and N + P addition enhanced GWP from 489 to 625 g CO2-eq m-2. The qPCR analysis revealed that decreased CH4 oxidation potential may lead to the enrichment of CH4 emissions under the hydrological alterations, and reduced nitrification and denitrification potential contributed to the reduction of N2O fluxes under all the treatments. Our study indicates that continuous flooding could curb the contribution of riparian GHGs fluxes to global warming but that the combination of N and P additions may increase the greenhouse effect mainly by regulating the CO2 emissions of growing season in riparian ecosystem.

Nano-selenium controlled cadmium accumulation and improved photosynthesis in indica rice cultivated in lead and cadmium combined paddy soils.

Selenium nanoparticles (Se NPs) are less toxic and more biocompatible than selenite or selenate. However, studies involving spraying with Se NPs for reducing accumulation of cadmium (Cd) and lead (Pb) in rice grains have been rarely reported as yet. Herein, indica rice seedlings cultivated in Cd+Pb-spiked paddy soils (denoted as positive control) were sprayed with Se NPs sols for four times from tillering to booting stage. Compared to positive control, 50-100 µmol/L Se NPs downregulated Cd transporters-related genes such as OsLCT1, OsHMA2 and OsCCX2 in leaves and OsLCT1, OsPCR1 and OsCCX2 genes in node I at filling stage. Meanwhile, Se-binding protein 1 was distinctly elevated, involving the repression of Cd and Pb transportation to rice grains. Se NPs also differentially improved RuBP carboxylase and chlorophylls especially some key genes and proteins involving photosynthetic system. Besides, 25-50 µmol/L Se NPs diminished reactive oxygen species overproduction from NADPH oxidases whereas boosted glutathione peroxidase, reducing protein carbonylation in rice seedlings. However, the antioxidant isozymes and oxidatively modified proteins were slightly rebounded at 100 µmol/L. Se contents were noticeably elevated and confirmed to exist as selenomethionine in the rice grains following all the treatments by Se NPs. Thus, the optimal dosage of Se NPs for foliar application is 50 µmol/L, which significantly decreased Cd accumulation, improved photosynthesis and Se enrichment whereas caused no distinct reduction of Pb in the grains. Thus, an appropriate dosage of Se NPs can be conducted to decrease Cd accumulation, improve photosynthesis, and organic Se contents in rice grains.

Endocrine disrupting effects of binary mixtures of 17ß-estradiol and testosterone in adult female western mosquitofish (Gambusia affinis).

Androgens and estrogens often co-exist in aquatic environments and pose potential risks to fish populations. However, little is known about the endocrine disrupting effects of the mixture of androgens and estrogens in fish. In this study, transcriptional level of target genes related to the hypothalamic-pituitary-gonadal-liver (HPGL) axis, sex hormone level, VTG protein concentration, histology and secondary sex characteristic were assessed in the ovaries and livers of adult female western mosquitofish (Gambusia affinis) exposed to 17ß-estradiol (E2), testosterone (T), and mixtures of E2 and T for 91 days. The results showed that the transcriptional expression of cytochrome P450, family 19, subfamily A, polypeptide 1a (Cyp19a1a) was suppressed in the 200 ng/L T treatment and the 50 ng/L E2 + 200 ng/L T treatment in the ovaries. Steroidogenic acute regulatory protein (Star) and Cyp11a1 showed a similar expression pattern in the T treatment to its corresponding T + E2 mixtures. In the ovaries, the concentrations of 17ß-estradiol and testosterone were decreased in most treatments compared with the solvent control. VTG protein was induced in all steroid treatment. However, exposure to T or E2 + T mixture did not cause the abnormal cells of the ovaries and livers and an extension of the anal fins in female G. affinis. This study demonstrates that chronic exposure to E2, T and their mixtures affects the transcripts of genes in the HPGL axis, steroid hormone level and VTG protein concentration in the ovaries and livers, but fails to cause the histopathological effect of the ovaries and livers and alter the morphology of the anal fins in G. affinis.

New insight into the negative impact of imidazolium-based ionic liquid [C10mim]Cl on Hela cells: From membrane damage to biochemical alterations.

As an alternative to volatile organic solvents, ionic liquids (ILs) are known as "green solvents", and widely used in industrial applications. However, due to their high solubility and stability, ILs have tendency to persist in the water environment, thus having potential negative impacts on the aquatic ecosystem. For assessing the environmental risks of ILs, a fundamental understanding of the toxic effects and mechanisms of ILs is needed. Here we evaluated the cytotoxicity of 1-methyl-3-decylimidazolium chloride ([C10mim]Cl) and elucidated the main toxic mechanism of [C10mim]Cl in human cervical carcinoma (Hela) cells. Microstructural analysis revealed that [C10mim]Cl exposure caused the cell membrane breakage, swollen and vacuolated mitochondria, and spherical cytoskeletal structure. Cytotoxicity assays found that [C10mim]Cl exposure increased ROS production, decreased mitochondrial membrane potential, induced cell apoptosis and cell cycle arrest. These results indicated that [C10mim]Cl could induce damage to cellular membrane structure, affect the integrity of cell ultrastructure, cause the oxidative damage and ultimately lead to the inhibition of cell proliferation. Moreover, alterations of biochemical information including the increased ratios of unsaturated fatty acid and carbonyl groups to lipid, and lipid to protein, and the decreased ratios of Amide I to Amide II, and α-helix to ß-sheet were observed in [C10mim]Cl treated cells, suggesting that [C10mim]Cl could affect the structure of membrane lipid alkyl chain and cell membrane fluidity, promote the lipid peroxidation and alter the protein secondary structure. The findings from this work demonstrated that membrane structure is the key target, and membrane damage is involved in [C10mim]Cl induced cytotoxicity.

Bidirectional Genetic Control of Phenotypic Heterogeneity and Its Implication for Cancer Drug Resistance.

Negative genetic regulators of phenotypic heterogeneity, or phenotypic capacitors/stabilizers, elevate population average fitness by limiting deviation from the optimal phenotype and increase the efficacy of natural selection by enhancing the phenotypic differences among genotypes. Stabilizers can presumably be switched off to release phenotypic heterogeneity in the face of extreme or fluctuating environments to ensure population survival. This task could, however, also be achieved by positive genetic regulators of phenotypic heterogeneity, or "phenotypic diversifiers," as shown by recently reported evidence that a bacterial divisome factor enhances antibiotic resistance. We hypothesized that such active creation of phenotypic heterogeneity by diversifiers, which is functionally independent of stabilizers, is more common than previously recognized. Using morphological phenotypic data from 4,718 single-gene knockout strains of Saccharomyces cerevisiae, we systematically identified 324 stabilizers and 160 diversifiers and constructed a bipartite network between these genes and the morphological traits they control. Further analyses showed that, compared with stabilizers, diversifiers tended to be weaker and more promiscuous (regulating more traits) regulators targeting traits unrelated to fitness. Moreover, there is a general division of labor between stabilizers and diversifiers. Finally, by incorporating NCI-60 human cancer cell line anticancer drug screening data, we found that human one-to-one orthologs of yeast diversifiers/stabilizers likely regulate the anticancer drug resistance of human cancer cell lines, suggesting that these orthologs are potential targets for auxiliary treatments. Our study therefore highlights stabilizers and diversifiers as the genetic regulators for the bidirectional control of phenotypic heterogeneity as well as their distinct evolutionary roles and functional independence.