Screening Probiotics for Anti-Helicobacter pylori and Investigating the Effect of Probiotics on Patients with Helicobacter pylori Infection.

Probiotics are natural microbial agents with beneficial properties such as bacteriostatic and anti-infective properties. Lactobacillus plantarum Q21, Q25 and QA85, were isolated from the Chinese specialty fermented food "Jiangshui" and proved to be highly resistant to Helicobacter pylori (p < 0.0001). In vitro results showed that Q21, Q25 and QA85 strongly inhibited H. pylori and could specifically co-aggregate H. pylori in vitro (more than 56%). Strains have the potential to adhere to cells and hinder H. pylori colonization (p < 0.0001). To assess the anti-H. pylori efficacy of strains in vivo, volunteers were recruited and a self-controlled study of probiotic intervention was conducted. Compared to pre-probiotics, volunteers who took Q21, Q25 and QA85 for 1 month showed significant improvement in discomfort, a significant reduction in GSRS scores (p < 0.05), and modulation of inflammatory response (p < 0.05). Q21, Q25 and QA85 resulted in a decreasing trend of H. pylori load in volunteers (454.30 ± 327.00 vs. 328.35 ± 237.19, p = 0.06). However, the strains were not significantly effective in modulating the imbalance of the gut microbiota caused by H. pylori infection. In addition, strains affect metabolic pathways by increasing the levels of O-Phosphoethanolamine and other related metabolites, which may ameliorate associated symptoms. Therefore, Lactobacillus plantarum Q21, Q25 and QA85 can be regarded as a candidate probiotic preparation that exerts direct or indirect anti-H. pylori effects by inhibiting H. pylori activity and colonization, reducing inflammation and discomfort, maintaining homeostasis in the internal environment, affecting the metabolic pathways and repairing the body barrier. They can play a role in relieving H. pylori infection.

Functional fractions of Astragalus polysaccharides as a potential prebiotic to alleviate ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine that is significantly influenced by an imbalance in the gut microbiota. Astragalus membranaceus, particularly its polysaccharide components, has shown therapeutic potential for the treatment of UC, although the specific active constituents and their mechanistic pathways remain to be fully elucidated. In this study, we investigated two molecular weight fractions of Astragalus polysaccharides (APS), APS1 (Mw < 10 kDa) and APS2 (10 kDa < Mw < 50 kDa), isolated by ultrafiltration, focusing on their prebiotic effects, effects on UC, and the underlying mechanism. Our results showed that both APS1 and APS2 exhibit prebiotic properties, with APS1 significantly outperforming APS2 in ameliorating UC symptoms. APS1 significantly attenuated weight loss and UC manifestations, reduced colonic pathology, and improved intestinal mucosal barrier integrity. In addition, APS1 significantly reduced the levels of inflammatory cytokines in the serum and colonic tissue, and downregulated colonic chemokines. Furthermore, APS1 ameliorated dextran sulfate sodium salt (DSS)-induced intestinal dysbiosis by promoting the growth of beneficial microbes and inhibiting the proliferation of potential pathogens, leading to a significant increase in short-chain fatty acids. In conclusion, this study highlights the potential of APS1 as a novel prebiotic for the prevention and treatment of UC.

Genome-wide methylation, transcriptome and characteristic metabolites reveal the balance between diosgenin and brassinosteroids in Dioscorea zingiberensis.

Diosgenin (DG) is a bioactive metabolite isolated from Dioscorea species, renowned for its medicinal properties. Brassinosteroids (BRs) are a class of crucial plant steroidal hormones. Cholesterol and campesterol are important intermediates of DG and BR biosynthesis, respectively. DG and BRs are structurally similar components; however, the regulatory network and metabolic interplays have not been fully elucidated. In an effort to decode these complex networks, we conducted a comprehensive study integrating genome-wide methylation, transcriptome and characteristic metabolite data from Dioscorea zingiberensis. Leveraging these data, we were able to construct a comprehensive regulatory network linking DG and BRs. Mass spectrometry results enabled us to clarify the alterations in cholesterol, campesterol, diosgenin, and castasterone (one of the major active BRs). The DG content decreased by 27.72% at 6 h after brassinolide treatment, whereas the content increased by 85.34% at 6 h after brassinazole treatment. Moreover, we pinpointed DG/BR-related genes, such as CASs, CYP90s, and B3-ARFs, implicated in the metabolic pathways of DG and BRs. Moreover, CASs and CYP90s exhibit hypomethylation, which is closely related to their high transcription. These findings provide robust evidence for the homeostasis between DG and BRs. In conclusion, our research revealed the existence of a balance between DG and BRs in D. zingiberensis. Furthermore, our work not only provides new insights into the relationship between the two pathways but also offers a fresh perspective on the functions of secondary metabolites.

Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation.

BACKGROUND: Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. METHODS AND RESULTS: miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. CONCLUSIONS: Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD.

Predictors of live-in migrant caregiver employment for people with dementia in Taiwan.

BACKGROUND: With the increasing number of individuals with dementia, families have hired an increasing number of live-in migrant caregivers (LIMCs). Currently, limited evidence is available regarding the influence of long-term care resource utilization on the hiring of LIMCs for caring for individuals with dementia in Taiwan. METHODS: We recruited individuals with dementia who did not hire LIMCs and their primary family caregivers from nine hospitals in Taiwan as baseline. Multivariable logistic regression was used to evaluate the utilization of long-term care resources for individuals with dementia and other factors that may affect the decision to hire LIMCs. RESULTS: The users of non-long-term care resources had the highest likelihood of hiring LIMCs (odds ratio [OR] = 4.24, 95% CI, 2.30-7.84). Compared with spouses, nonimmediate family caregivers (OR = 3.40, 95% CI, 1.16-9.90) were significantly more likely to hire LIMCs. A higher likelihood of hiring LIMCs was observed for those with Lewy body dementia compared with other individuals (OR = 2.31, 95% CI, 1.03-5.14). Compared with individuals who did not hire LIMCs, those who hired LIMCs exhibited higher scores on the Neuropsychiatric Inventory (NPI) and higher severity of individual NPI items. CONCLUSION: Hiring LIMCs is strongly correlated with the utilization of non-long-term care resources and is influenced by the dynamics between individuals with dementia and their primary family caregivers. A higher likelihood of hiring LIMCs was observed for individuals with Lewy body dementia and individuals with elevated NPI scores compared with their counterparts. Given these observations, various support strategies and interventions should be tailored to the specific requirements of individuals with dementia and their families.

Medication Dosage Impact on Mortality in Old-Age Individuals with Schizophrenia: A National Cohort Study.

As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the 'no exposure' category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS.

Integrated evolutionary pattern analyses reveal multiple origins of steroidal saponins in plants.

Steroidal saponins are a class of specialized metabolites essential for plant's response to biotic and abiotic stresses. They are also important raw materials for the industrial production of steroid drugs. Steroidal saponins are present in some monocots, such as Dioscorea and Paris, but their distribution, origin, and evolution in plants remain poorly understood. By reconstructing the evolutionary history of the steroidal saponin-associated module (SSAM) in plants, we reveal that the steroidal saponin pathway has its origin in Asparagus and Dioscorea. Through evaluating the distribution and evolutionary pattern of steroidal saponins in angiosperms, we further show that steroidal saponins originated multiple times in angiosperms, and exist in early diverged lineages of certain monocot lineages including Asparagales, Dioscoreales, and Liliales. In these lineages, steroidal saponins are synthesized through the high copy and/or high expression mechanisms of key genes in SSAM. Together with shifts in gene evolutionary rates and amino acid usage, these molecular mechanisms shape the current distribution and diversity of steroidal saponins in plants. Consequently, our results provide new insights into the distribution, diversity and evolutionary history of steroidal saponins in plants, and enhance our understanding of plants' resistance to abiotic and biotic stresses. Additionally, fundamental understanding of the steroidal saponin biosynthesis will facilitate their industrial production and pharmacological applications.

The Functional Characterization of DzCYP72A12-4 Related to Diosgenin Biosynthesis and Drought Adaptability in Dioscorea zingiberensis.

Dioscorea zingiberensis is a perennial herb famous for the production of diosgenin, which is a valuable initial material for the industrial synthesis of steroid drugs. Sterol C26-hydroxylases, such as TfCYP72A616 and PpCYP72A613, play an important role in the diosgenin biosynthesis pathway. In the present study, a novel gene, DzCYP72A12-4, was identified as C26-hydroxylase and was found to be involved in diosgenin biosynthesis, for the first time in D. zingiberensis, using comprehensive methods. Then, the diosgenin heterogenous biosynthesis pathway starting from cholesterol was created in stable transgenic tobacco (Nicotiana tabacum L.) harboring DzCYP90B71(QPZ88854), DzCYP90G6(QPZ88855) and DzCYP72A12-4. Meanwhile, diosgenin was detected in the transgenic tobacco using an ultra-performance liquid chromatography system (Vanquish UPLC 689, Thermo Fisher Scientific, Bremen, Germany) tandem MS (Q Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer, Thermo Fisher Scientific, Bremen, Germany). Further RT-qPCR analysis showed that DzCYP72A12-4 was highly expressed in both rhizomes and leaves and was upregulated under 15% polyethylene glycol (PEG) treatment, indicating that DzCYP72A12-4 may be related to drought resistance. In addition, the germination rate of the diosgenin-producing tobacco seeds was higher than that of the negative controls under 15% PEG pressure. In addition, the concentration of malonaldehyde (MDA) was lower in the diosgenin-producing tobacco seedlings than those of the control, indicating higher drought adaptability. The results of this study provide valuable information for further research on diosgenin biosynthesis in D. zingiberensis and its functions related to drought adaptability.

Preoperative 18F-FDG PET/CT radiomics analysis for predicting HER2 expression and prognosis in gastric cancer.

Background: We aimed to establish and validate 2 machine learning models using 18F-flurodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomic features to predict human epidermal growth factor receptor 2 (HER2) expression and prognosis in gastric cancer (GC) patients. Methods: We retrospectively enrolled 90 patients diagnosed with GC, including their clinical information and the 18F-FDG PET/CT images. Patients were allocated to a training cohort of 72 patients and an independent validation cohort (IVC) of 18 patients. There were 2,100 radiomic features extracted from the 18F-FDG PET/CT scans. A sequential combination of multivariate and univariate feature selection was applied, including sequential forward selection and a redundancy-based analysis. The justification of the model performance was conducted by cross-validation analysis on the training set and an independent validation analysis. Results: The machine learning models were developed using a balanced bagging approach for HER2 expression prediction and prognosis prediction, which differentiated HER2 positive expression from negative expression in the IVC with an area under the receiver operating characteristic curve (AUC) of 0.72, sensitivity of 0.85, and specificity of 0.80. The IVC for prognosis prediction achieved an AUC of 0.75, sensitivity of 0.82, and specificity of 0.71. We also conducted a reasonable interpretation for the selected features in each classification task from multiple aspects, including normalized feature importance analysis and statistical correlation analysis with the clinical features that were defaulted to be effective. Conclusions: 18F-FDG PET/CT radiomics analysis with a machine learning model provides a quantitative, efficient, and objective mechanism for predicting HER2 expression and prognosis in GC patients.

Advances in the Biosynthesis and Molecular Evolution of Steroidal Saponins in Plants.

Steroidal saponins are an important type of plant-specific metabolite that are essential for plants' responses to biotic and abiotic stresses. Because of their extensive pharmacological activities, steroidal saponins are also important industrial raw materials for the production of steroidal drugs. In recent years, more and more studies have explored the biosynthesis of steroidal saponins in plants, but most of them only focused on the biosynthesis of their molecular skeleton, diosgenin, and their subsequent glycosylation modification mechanism needs to be further studied. In addition, the biosynthetic regulation mechanism of steroidal saponins, their distribution pattern, and their molecular evolution in plants remain unclear. In this review, we summarized and discussed recent studies on the biosynthesis, molecular regulation, and function of steroidal saponins. Finally, we also reviewed the distribution and molecular evolution of steroidal saponins in plants. The elucidation of the biosynthesis, regulation, and molecular evolutionary mechanisms of steroidal saponins is crucial to provide new insights and references for studying their distribution, diversity, and evolutionary history in plants. Furthermore, a deeper understanding of steroidal saponin biosynthesis will contribute to their industrial production and pharmacological applications.

Fermented Astragalus and its metabolites regulate inflammatory status and gut microbiota to repair intestinal barrier damage in dextran sulfate sodium-induced ulcerative colitis.

Fermentation represents an efficient biotechnological approach to increase the nutritional and functional potential of traditional Chinese medicine. In this study, Lactobacillus plantarum was used to ferment traditional Chinese medicine Astragalus, the differential metabolites in the fermented Astragalus (FA) were identified by ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS), and the ameliorating effect of FA on dextran sulfate sodium (DSS)-induced colitis in mice were further explored. The results showed that 11 differential metabolites such as raffinose, progesterone and uridine were identified in FA, which may help improve the ability of FA to alleviate colitis. Prophylactic FA supplementation effectively improved DAI score, colon length and histopathological lesion in DSS-treated mice. The abnormal activation of the intestinal immune barrier in mice was controlled after FA supplementation, the contents of myeloperoxidase (MPO) and IgE were reduced and the contents of IgA were increased. The intestinal pro-inflammatory factors TNF-α, IL-1ß, IL-6, and IL-17 were down-regulated and the anti-inflammatory factors IL-10 and TGF-ß were up-regulated, suggesting that FA can intervene in inflammatory status by regulating the balance of Th1/Th2/Th17/Treg related cytokines. In addition, FA supplementation modified the structure of the intestinal microbiota and enriched the abundance of Akkermansia and Alistipes, which were positively associated with the production of short-chain fatty acids. These microbes and their metabolites induced by FA also be involved in maintaining the intestinal mucosal barrier integrity by affecting mucosal immunity. We observed that intestinal tight junction protein and mucous secreting protein ZO-1, occludin, and MUC2 genes expression were more pronounced in mice supplemented with FA compared to unfermented Astragalus, along with modulation of intestinal epithelial cells (IECs) apoptosis, verifying the intestinal mucosal barrier repaired by FA. This study is the first to suggest that FA as a potential modulator can more effectively regulate the inflammatory status and gut microbiota to repair the intestinal barrier damage caused by colitis.

Comparative transcriptome analysis reveals key genes for polyphyllin difference in five Paris species.

Paris species accumulate a large amount of steroidal saponins, which have numerous pharmacological activities and have become an essential component in many patented drugs. However, only two among all Paris species. Paris are identified as official sources due to high level of bioactive compounds. To clarify the composition of steroidal saponins and the molecular basis behind the differences between species, we investigated transcriptome and metabolic profiles of leaves and rhizomes in Paris polyphylla var. chinensis (PPC), Paris polyphylla var. yunnanensis (PPY), Paris polyphylla var. stenophylla (PPS), Paris fargesii (PF), and Paris mairei (PM). Phytochemical results displayed that the accumulation of steroidal saponins was tissue- and species-specific. PF and PPS contained more steroidal saponins in leaves than rhizomes, while PPY accumulated more steroidal saponins in rhizomes than leaves. PPC and PM contained similar amounts of steroidal saponins in leaves and rhizomes. Transcriptome analysis illustrated that most differentially expressed genes related to the biosynthesis of steroidal saponins were abundantly expressed in rhizomes than leaves. Meanwhile, more biosynthetic genes had significant correlations with steroidal saponins in rhizomes than in leaves. The result of CCA indicated that ACAT, DXS, DWF1, and CYP90 constrained 97.35% of the variance in bioactive compounds in leaves, whereas CYP72, UGT73, ACAT, and GPPS constrained 98.61% of the variance in phytochemicals in rhizomes. This study provided critical information for enhancing the production of steroidal saponins by biotechnological approaches and methodologies.

Supply of basic necessities to vulnerable populations during the COVID-19 pandemic: Empirical evidence from Shanghai, China.

Background: In spite of initial widespread skepticism, city lockdown has been proved to be an effective short-term tool in containing and delaying the spread of a viral epidemic. The measures to ensure the supply of the basic necessities adequately and equitably, especially for those vulnerable ones has become a major challenge faced by all countries taking a city lockdown measure during the epidemic. Methods: Data was collected through relevant government documents, work records, policy reports, media reports and the online-work information platform designed by the research group. Based on these references, the study analyzed the mainly technical difficulties and the countermeasures of the supply process, and summarized the key characteristics of basic necessities supply strategy for vulnerable groups in Shanghai. Results: The supply strategy for vulnerable groups in Shanghai covers 16 districts, 232 streets and 6,028 neighborhood communities, which has already been in test running in April in some districts. The practical experience in Shanghai solved three key materials supply problems (lack of purchase channels, insufficient material reserves, insufficient transportation capacity) faced by government during the city lockdown, and showed three essential characteristics (overall coordination, community-centered intervention, technical support). Conclusions: The findings in this study may provide some suggestions to other countries about how to better manage the preparation, dispatch and transportation of basic necessities in shortage for those vulnerable ones during the city lockdown.

The genome of Dioscorea zingiberensis sheds light on the biosynthesis, origin and evolution of the medicinally important diosgenin saponins.

Diosgenin saponins isolated from Dioscorea species such as D. zingiberensis exhibit a broad spectrum of pharmacological activities. Diosgenin, the aglycone of diosgenin saponins, is an important starting material for the production of steroidal drugs. However, how plants produce diosgenin saponins and the origin and evolution of the diosgenin saponin biosynthetic pathway remain a mystery. Here we report a high-quality, 629-Mb genome of D. zingiberensis anchored on 10 chromosomes with 30 322 protein-coding genes. We reveal that diosgenin is synthesized in leaves ('source'), then converted into diosgenin saponins, and finally transported to rhizomes ('sink') for storage in plants. By evaluating the distribution and evolutionary patterns of diosgenin saponins in Dioscorea species, we find that diosgenin saponin-containing may be an ancestral trait in Dioscorea and is selectively retained. The results of comparative genomic analysis indicate that tandem duplication coupled with a whole-genome duplication event provided key evolutionary resources for the diosgenin saponin biosynthetic pathway in the D. zingiberensis genome. Furthermore, comparative transcriptome and metabolite analysis among 13 Dioscorea species suggests that specific gene expression patterns of pathway genes promote the differential evolution of the diosgenin saponin biosynthetic pathway in Dioscorea species. Our study provides important insights and valuable resources for further understanding the biosynthesis, evolution, and utilization of plant specialized metabolites such as diosgenin saponins.

Potential Factors Contributing to Ozone Production in AQUAS-Kyoto Campaign in Summer 2020: Natural Source-Related Missing OH Reactivity and Heterogeneous HO2/RO2 Loss.

This study presents total OH reactivity, ancillary trace species, HO2 reactivity, and complex isoprene-derived RO2 reactivity due to ambient aerosols measured during the air quality study (AQUAS)-Kyoto campaign in September, 2020. Observations were conducted during the coronavirus disease (COVID-19) pandemic (associated with reduced anthropogenic emissions). The spatial distribution of missing OH reactivity highlights that the origin of volatile organic compounds (VOCs) may be from natural-emission areas. For the first time, the real-time loss rates of HO2 and RO2 onto ambient aerosols were measured continuously and alternately. Ozone production sensitivity was investigated considering unknown trace species and heterogeneous loss effects of XO2 (≡HO2 + RO2) radicals. Missing OH reactivity enhanced the ozone production potential by a factor of 2.5 on average. Heterogeneous loss of radicals could markedly suppress ozone production under low NO/NOx conditions with slow gas-phase reactions of radicals and change the ozone regime from VOC- to NOx-sensitive conditions. This study quantifies the relationship of missing OH reactivity and aerosol uptake of radicals with ozone production in Kyoto, a low-emission suburban area. The result has implications for future NOx-reduction policies. Further studies may benefit from the combination of chemical transport models and inverse modeling over a wide spatiotemporal range.

Effect of exogenous jasmonic acid on physiology and steroidal saponin accumulation in Dioscorea zingiberensis.

Dioscorea zingiberensis is a valuable medicinal herb rich in steroidal saponins. To reveal the role of jasmonic acid (JA) on physiology and steroidal saponins accumulation, D. zingiberensis were treated with different concentrations of JA. The antioxidant capacity, photosynthetic parameters, fatty acids and metabolites related to steroidal saponins biosynthesis (phytosterols, diosgenin and steroidal saponins) were examined under JA treatment. The results demonstrated that JA treatment caused a great reduction in MDA, stomatal width, photosynthetic rate and photosynthetic pigment, induced a considerable increase in proline, soluble sugar, soluble protein and antioxidant enzymes (CAT, POD and SOD), and leaded to a significant up-regulation in the expression of genes related to antioxidant system and chlorophyll degradation. Specialized metabolites displayed various changes under different concentrations of JA. The majority of fatty acids exhibited negative responses to JA treatment in leaf and rhizome. In leaf, JA treatment enhanced the accumulation of phytosterols and diosgenin, but decreased the accumulation of steroidal saponins. However, steroidal saponins were mainly accumulated in rhizome and were highly increased by JA treatment. Redundancy analysis illustrated that fatty acids were strongly associated with metabolites related to steroidal saponins. Among all fatty acids, C16:0, C18:1, C18:3, C22:0 and C24:0 contributed most to the variation in metabolites related to steroidal saponin biosynthesis. Overall, JA treatment leaded to an increase in steroidal saponins, but an inhibition of plant growth. Thus, the negative effects of JA application on plant physiology should be carefully assessed before being utilized to increase the production of steroidal saponins in D. zingiberensis.

Redox-Active Crystalline Coordination Catalyst for Hybrid Electrocatalytic Methanol Oxidation and CO2 Reduction.

Hybrid CO2 electroreduction (HCER) is recognized as an important strategy to improve the total value of redox products and energy conversion efficiency. In this work, a coordination catalyst model system (Ni8 -TET with active oxidation sites, Ni-TPP with active reduction sites and PCN-601 with redox-active sites) for HCER was established for the first time. Especially, PCN-601 can complete both anodic methanol oxidation and cathodic CO2 reduction with FEHCOOH and FECO over 90 %. The performance can be further improved with light irradiation (FE nearly 100 %). DFT calculations reveal that the transfer of electrons from NiII 8 clusters to metalloporphyrins under electric fields results in the raised oxidizability of Ni8 clusters and the raised reducibility of metalloporphyrin, which then improves the electrocatalytic performance. This work serves as a well-defined model system and puts forward a new design idea for establishing efficient catalysts for hybrid CO2 electroreduction.

Metabolic Activation and Cytotoxicity of Propafenone Mediated by CYP2D6.

Propafenone (PPF) is a class IC antidysrhythmic drug, which is commonly used for the treatment of atrial fibrillation and other supraventricular arrhythmias. It is also a ß-adrenoceptor antagonist that can cause bradycardia and bronchospasm. Hepatotoxicity is one of the adverse reactions reported, with clinical manifestations including acute cholestasis and hepatocyte necrosis. However, the mechanism of PPF-induced hepatotoxicity remains unclear. The present study was conducted to identify reactive metabolite(s) to determine related metabolic pathways and define the possible association of the bioactivation with PPF cytotoxicity. An O-demethylation phase I metabolite (M1), a further position C5 hydroxylation (para-position of the benzene ring) metabolite (M2), glutathione (GSH) conjugates (M3 and M4), and N-acetylcysteine (NAC) conjugates (M5 and M6) were detected in rat liver microsomal incubations containing PPF and GSH or NAC as trapping agents. The corresponding GSH conjugates and NAC conjugates were found in the bile and urine of rats after PPF administration, respectively. The observed GSH and NAC conjugates indicate that a quinone metabolite was generated in vitro and in vivo. Recombinant P450 enzyme incubations showed that CYP2D6 was the principal enzyme catalyzing this metabolic activation. Quinidine, a selective inhibitor of CYP2D6, attenuated the susceptibility of hepatocytes to the cytotoxicity of PPF. The results suggest that PPF was metabolized to a p-quinone intermediate which may be involved in PPF-induced hepatotoxicity.

Community structure and function of epiphytic bacteria attached to three submerged macrophytes.

In aquatic ecosystems, large amounts of epiphytic bacteria living on the leaf surfaces of submerged macrophytes play important roles in affecting plant growth and biogeochemical cycling. The restoration of different submerged macrophytes has been considered an effective measure to improve eutrophic lakes. However, the community ecology of epiphytic bacteria is far from well understood for different submerged macrophytes. In this study, we used quantitative PCR, 16S rRNA gene high-throughput sequencing and functional prediction analysis to explore the structure and function of epiphytic bacteria in an aquatic ecosystem recovered by three submerged macrophytes (Hydrilla verticillata, Vallisneria natans and Potamogeton maackianus) during two growth periods. The results showed that the community compositions and functions of epiphytic bacterial communities on the submerged macrophyte hosts were different from those of the planktonic bacterial communities in the surrounding water. The alpha diversity of the epiphytic bacterial community was significantly higher in October than in July, and the community compositions and functions differed significantly in July and October. Among the three submerged macrophytes, the structures and functions of the epiphytic bacterial community exhibited obvious differences, and some specific taxa were enriched on the biofilms of the three plants. The alpha diversity and the abundance of functions related to nitrogen and phosphorus transformation were higher in the epiphytic bacteria of P. maackianus. In summary, these results provide clues for understanding the distribution and formation mechanisms of epiphytic bacteria on submerged macrophyte leaves and their roles in freshwater ecosystems.

Genome-Wide Identification of CYP72A Gene Family and Expression Patterns Related to Jasmonic Acid Treatment and Steroidal Saponin Accumulation in Dioscorea zingiberensis.

Dioscorea zingiberensis is a medicinal herb containing a large amount of steroidal saponins, which are the major bioactive compounds and the primary storage form of diosgenin. The CYP72A gene family, belonging to cytochromes P450, exerts indispensable effects on the biosynthesis of numerous bioactive compounds. In this work, a total of 25 CYP72A genes were identified in D. zingiberensis and categorized into two groups according to the homology of protein sequences. The characteristics of their phylogenetic relationship, intron-exon organization, conserved motifs and cis-regulatory elements were performed by bioinformatics methods. The transcriptome data demonstrated that expression patterns of DzCYP72As varied by tissues. Moreover, qRT-PCR results displayed diverse expression profiles of DzCYP72As under different concentrations of jasmonic acid (JA). Likewise, eight metabolites in the biosynthesis pathway of steroidal saponins (four phytosterols, diosgenin, parvifloside, protodeltonin and dioscin) exhibited different contents under different concentrations of JA, and the content of total steroidal saponin was largest at the dose of 100 µmol/L of JA. The redundant analysis showed that 12 DzCYP72As had a strong correlation with specialized metabolites. Those genes were negatively correlated with stigmasterol and cholesterol but positively correlated with six other specialized metabolites. Among all DzCYP72As evaluated, DzCYP72A6, DzCYP72A16 and DzCYP72A17 contributed the most to the variation of specialized metabolites in the biosynthesis pathway of steroidal saponins. This study provides valuable information for further research on the biological functions related to steroidal saponin biosynthesis.