Involvement of the 4-coumarate:coenzyme A ligase 4CL4 in rice phosphorus acquisition and rhizosphere microbe recruitment via root growth enlargement.

MAIN CONCLUSION: The 4-coumarate:coenzyme A ligase 4CL4 is involved in enhancing rice P acquisition and use in acid soil by enlarging root growth and boosting functional rhizosphere microbe recruitment. Rice (Oryza sativa L.) cannot easily acquire phosphorus (P) from acid soil, where root growth is inhibited and soil P is fixed. The combination of roots and rhizosphere microbiota is critical for plant P acquisition and soil P mobilization, but the associated molecular mechanism in rice is unclear. 4CL4/RAL1 encodes a 4-coumarate:coenzyme A ligase related to lignin biosynthesis in rice, and its dysfunction results in a small rice root system. In this study, soil culture and hydroponic experiments were conducted to examine the role of RAL1 in regulating rice P acquisition, fertilizer P use, and rhizosphere microbes in acid soil. Disruption of RAL1 markedly decreased root growth. Mutant rice plants exhibited decreased shoot growth, shoot P accumulation, and fertilizer P use efficiency when grown in soil-but not under hydroponic conditions, where all P is soluble and available for plants. Mutant ral1 and wild-type rice rhizospheres had distinct bacterial and fungal community structures, and wild-type rice recruited some genotype-specific microbial taxa associated with P solubilization. Our results highlight the function of 4CL4/RAL1 in enhancing rice P acquisition and use in acid soil, namely by enlarging root growth and boosting functional rhizosphere microbe recruitment. These findings can inform breeding strategies to improve P use efficiency through host genetic manipulation of root growth and rhizosphere microbiota.

Decrease in hemicellulose content and its retention of iron contributes to phosphorus deficiency alleviated iron deficiency in Arabidopsis thaliana.

The physiological and molecular mechanisms between phosphorus (P) and iron (Fe) interactions are still elusive although they have been extensively investigated. In this study, we uncovered that limiting P supply could alleviate Fe deficiency in Arabidopsis (Col-0). Under Fe deficiency, P deficiency (-Fe-P) decreased cell wall Fe accumulation in root, but elevated Fe accumulation in the shoot, implying that the reduced Fe retention in the root cell wall may contribute to the P-deficiency-alleviated Fe deficiency in the shoot. On the other hand, increasing P supply could mimic the degree of Fe deficiency in terms of the expressions of genes induced after Fe deficient treatment. The components of the root cell wall showed that there was no distinction in the pectin content and the Fe retention in pectin between -Fe and -Fe-P treatments, while hemicellulose 1 content and Fe retained in it were decreased significantly in -Fe-P treatment as compared with -Fe treatment. The time-course experiment showed that decreasing cell wall retained Fe was mainly from the corresponding decrease in hemicellulose 1 retained Fe. Furthermore, the up-regulation of IRT1 expression in -Fe-P was obviously lower than -Fe. All these suggest that the P deficiency-induced decrease of hemicellulose 1 component leads to reutilization of root cell wall Fe and improvement of Fe nutrition in shoot in Fe deficient Arabidopsis. Our results provide a novel explanation of the interplay between Fe and P in Arabidopsis.

Auxin facilitates cell wall phosphorus reutilization in a nitric oxide-ethylene dependent manner in phosphorus deficient rice (Oryza sativa L.).

Auxin is involved in stress responses of plants, such as phosphorus (P) deficiency in rice. Studies on whether auxin participates in cell-wall inorganic phosphorous (Pi) reutilization in Pi-starved rice are scarce. This study explored the mechanisms underlying auxin-facilitated cell-wall Pi-reutilization in rice roots. Pi deficiency rapidly induced auxin accumulation in roots; exogenous auxin [α-naphthaleneacetic acid (NAA), a permeable analog of auxin] elevated soluble Pi content in roots and shoots by increasing pectin content by enhancing activity of pectin methylesterase, and upregulating the transcript level of PHOSPHORUS-TRANSPORTER-2, such that more Pi was translocated to the shoot. Irrespective of the Pi status, exogenous auxin induced nitric oxide (NO) and ethylene production, while exogenous sodium nitroprusside (an NO donor) and 1-aminocyclopropane-1-carboxylic acid (a precursor of ethylene) had no effect on auxin content, suggesting that auxin may act upstream of NO and ethylene. The beneficial effect of NAA in increasing soluble Pi content in roots and shoots disappeared when 2-(4-carboxyphenyl)- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (a scavenger of NO) or aminoethoxyvinylglycine (an inhibitor of ethylene) were applied, suggesting that auxin facilitates cell-wall Pi-reutilization in a NO-ethylene-dependent manner in Pi-deficient rice. Our study results suggest auxin application as an effective agronomic practice for improving plant Pi nutrition in P-deficient conditions.

Visualization and Bibliometric Analysis of Research Trends on Hyperbaric Oxygen Therapy.

Hyperbaric oxygen therapy (HBOT) is a professional medical regimen with a wide range of clinical applications in various research fields. In addition to treating diving decompression sickness and air embolism, HBOT is used as an adjuvant in the management of various diseases. A large number of studies have been published to confirm its efficacy. Although HBOT has been clinically applied to the treatment of many diseases, the effectiveness of these treatments remains controversial. Exploring and evaluating HBOT will contribute to the future development of research in this field. Through a quantitative analysis of the literature, this paper explores the citation relevance and collaboration map and their impact on research outcomes. This study used bibliometric and cartographic techniques with VOSviewer to identify the most influential countries and scholars using this treatment, based on syndrome differentiation. It also provides continuous quality evaluation and lean management of the medical expenses associated with HBOT.

Clinical Efficacy of Dienogest versus Levonorgestrel-Releasing Intrauterine System for Adenomyosis.

Objective: The aim of this study is to evaluate the efficacy of dienogest versus levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of adenomyosis. Methods: In this retrospective study, 85 patients with adenomyosis treated in The First Affiliated Hospital of Zhengzhou University from May 2019 to May 2021 were recruited and assigned, via the random number table method at a ratio of 1 : 1, to receive either dienogest (observation group, n = 41) or LNG-IUS (control group, n = 44). The patients presented with dysmenorrhea, menorrhagia, and infertility. The treatment outcome was evaluated using visual analogue scale (VAS) scores, menstrual volume, uterine volume, endometrial thickness, and adverse reactions. Results: After treatment, the VAS score, menstrual volume, and endometrial thickness were significantly decreased in both groups (P < 0.05). After 3, 6, and 12 months of treatment, patients receiving dienogest showed significantly lower VAS scores compared to those treated with LNG-IUS (P < 0.05). After 6 and 12 months of treatment, patients receiving dienogest were also found to have a significantly better control of menstrual volume compared to those receiving LNG-IUS (P < 0.05). Irregular vaginal bleeding was mainly seen in the first 3 months of treatment with dienogest. The incidence of irregular vaginal bleeding lasting more than 6 months was lower with LNG-IUS treatment than with dienogest (P < 0.05), and it decreased in both groups as the duration of treatment increased. Conclusion: Dienogest effectively alleviates dysmenorrhea, relieves pelvic pain, dyspareunia, and reduces menstrual flow in patients with adenomyosis, with few adverse effects and a high safety profile.

Putrescine is involved in root cell wall phosphorus remobilization in a nitric oxide dependent manner.

Phosphorus (P) deficiency is a key limited factor to affect the crop production in rice (Oryza sativa). Recently, accumulating evidences have shown that root cell wall P reutilization could be released to the cytoplasm to alleviate the P starvation and a set of plant hormone and signal molecules have been identified to be involved in it. However, the role of putrescine (Put) in this process is still unknown. In this study, we found that Put with a concentration of 0.001 mM, 0.01 mM and 0.1 mM increased the root and shoot biomass in Nipponbare (Nip) and Kasalath (Kas) under P deficiency, although only 0.1 mM Put could significantly elevated the root and shoot soluble P concentration in Nip. Exogenous 0.1 mM Put treatment reduced the root cell wall P content through increasing the pectin content and pectin methylesterase (PME) activity, indicating that Put can be involved in the root cell wall P reutilization under P starvation. In addition, Put treatment also stimulated the root-to-shoot translocation of P through upregulating the expression of PHOSPHORUS TRANSPORTER 2 (OsPT2) and OsPT8 that responsible for the long-distance transport. Put under P-deficient condition significantly enhanced the Nitric Oxide (NO) accumulation in root and the application of NO inhibitor carboxy-PTIO (cPTIO) could reverse the Put-alleviated P-deficient phenotype, suggesting this process is mediated by NO. In conclusion, our results demonstrated that Put acts upstream of NO to activate the root cell wall P remobilization in rice.

Jasmonic acid is involved in root cell wall phosphorus remobilization through the nitric oxide dependent pathway in rice.

Jasmonic acid (JA) is involved in phosphorus (P) stress in plants, but its underlying molecular mechanisms are still elusive. In this study, we found root endogenous JA content in rice increased under P deficiency (-P), suggesting that JA might participate in P homeostasis in plants. This hypothesis was further confirmed through the addition of exogenous JA (+JA), as this could increase both the root and shoot soluble P content through regulating root cell wall P reutilization. In addition, -P+JA treatment significantly induced the expression of P transporter gene OsPT2, together with increased xylem P content, implying that JA is also important for P translocation from the root to the shoot in P-deficient rice. Furthermore, the accumulation of the molecular signal nitric oxide (NO) was enhanced under -P+JA treatment when compared with -P treatment alone, while the addition of c-PTIO, a scavenger of NO, could reverse the P-deficient phenotype alleviated by JA. Taken together, our results reveal a JA-NO-cell wall P reutilization pathway under P deficiency in rice.

Nimbolide inhibits 2D and 3D prostate cancer cells migration, affects microtubules and angiogenesis and suppresses B-RAF/p.ERK-mediated in vivo tumor growth.

BACKGROUND: Prostate cancer (PCa) is the most prominent malignancy among men worldwide. PCa cells have a high tendency to metastasize to various distant organs, and this activity is the main cause of PCa mortality. Nimbolide is a promising phytochemical constituent of neem Azadirachta indica (Meliaceae). Previous studies showed that nimbolide exhibited potent anticancer activity however, its role against PCa tumorigenesis has not been fully elucidated. PURPOSE: Our work aims to explore the role of nimbolide in regulating the essential tumor-associated processes involved in the metastatic cascade in PCa cells. STUDY DESIGN: Cytotoxicity assay, wound healing and spheroid invasion assays, western blotting, immunofluorescence, tube-formation assay, in vivo and immunohistochemistry. METHODS: The cytotoxicity of nimbolide towards PCa cell lines was assessed by resazurin assays. The cell mobility and migration of nimbolide-treated DU145 cells were determined by wound healing and spheroid invasion assays. Tubulin network was visualized using U2OS cells and DU145 cells. The effect of nimbolide on E-cadherin, ß-catenin, acetylated α-tubulin and HDAC6 protein expressions levels were measured by Western blot. The potentiality of nimbolide to inhibit angiogenesis was revealed by HUVEC tube-formation assay. Nimbolide antitumor effect was studied in a syngeneic model of murine prostate cancer. RESULTS: The current study indicated that nimbolide negatively affected the migratory and invasive capacity of DU145 prostate cancer cells in 2D and three-dimensional (3D) spheroid cultures. Interestingly, nimbolide induced downregulation of E-cadherin without any influence on the expression level of ß-catenin. Additionally, we demonstrated that nimbolide influenced the microtubule network which was supported by the upregulation of acetylated α-tubulin and the reduction in HDAC6 protein. Moreover, the inhibitory effect of nimbolide on angiogenesis was clearly observed in HUVEC tube formation assay. In vivo experiments revealed the significant suppression of PCa growth and targeting of the B-RAF/p.ERK signaling pathway by nimbolide. CONCLUSION: Our results showed that nimbolide inhibited 2D and 3D prostate cancer cells migration and downregulated E-cadherin protein expression, a marker for metastatic chemoresistance and tumor recurrence. Nimbolide stabilized the microtubules, combated angiogenesis and suppressed B.RAF/ERK-mediated in vivo tumor growth. Nimbolide may be considered as potential therapeutic agent for metastatic and advanced PCa patients and merits further investigations.

[Network Meta-analysis of efficacy and safety of Chinese patent medicines in treatment of insomnia].

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of insomnia by frequency network Meta-analysis. Randomized controlled trials of Chinese patent medicines for insomnia were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase and Cochrane Library databases from the time of database establishment to October 2020. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 11 kinds of Chinese patent medicines in 27 RCTs were included. According to Meta-analysis, in term of the effective rate, Tianmeng Liquid, Zaoren Anshen Capsules, Shumian Capsules, Shensong Yangxin Capsules, Shenqi Wuweizi Tablets, Shugan Jieyu Capsules, Anshen Bunao Liquid and Qiye Anshen Tablets combined with nonbenzodiazepine drugs(NBZDs) were superior to NBZDs alone. In term of the improvement of Pittsburg sleeping quality index(PSQI) score, Tianmeng Liquid, Shumian Capsules, Shensong Yangxin Capsules, Bailemian Capsules, Shenqi Wuweizi Tablets, Shugan Jieyu Capsules, Yangxue Qingnao Granules and Yindan Xinnaotong Capsules combined with NBZDs were superior to NBZDs alone. In terms of the safety, Shumian Capsules, Shensong Yangxin Capsules, Shenqi Wuweizi Tablets and Qiye Anshen Tablets combined with NBZDs were superior to NBZDs alone. In terms of the avoidance of dizziness and headache, Qiye Anshen Tablets combined with NBZDs were superior to NBZDs alone. The results of Network Meta-analysis indicated that in term of the effective rate, top three optimal medication regimens were NBZDs combined with Shugan Jieyu Capsules, combined with Zaoren Anshen Capsules and combined with Shensong Yangxin Capsules in the order from high to low. With the respect of improvement of PSQI score, top three optimal medication regimens were NBZDs combined with Yangxue Qingnao Granules, combined with Tianmeng Liquid and combined with Yindan Xinnaotong Capsules in the order from high to low. In terms of the safety, top three optimal medication regimens were NBZDs combined with Qiye Anshen Tablets, combined with Shensong Yangxin Capsules and combined with Shenqi Wuweizi Tablets in the order from high to low. In terms of the avoidance of dizziness and headache, top three optimal medication regimens were NBZDs combined with Qiye Anshen Tablets, combined with Zaoren Anshen Capsules and combined with Shumian Capsules in the order from high to low. In terms of the avoidance of fatigue, top three optimal medication regimens were NBZDs combined with Shensong Yangxin Capsules, combined with Shumian Capsules and combined with Qiye Anshen Tablets in the order from high to low. In conclusion, Chinese patent medicines combined with NBZDs can effectively alleviate the symptoms of insomnia with a high safety. However, the conclusion of this study needs to be verified by more high-quality studies because of the low methodological quality of the included studies.

Saponins isolated from Radix polygalae extent lifespan by modulating complement C3 and gut microbiota.

With the increase in human lifespan, population aging is one of the major problems worldwide. Aging is an irreversible progressive process that affects humans via multiple factors including genetic, immunity, cellular oxidation and inflammation. Progressive neuroinflammation contributes to aging, cognitive malfunction, and neurodegenerative diseases. However, precise mechanisms or drugs targeting age-related neuroinflammation and cognitive impairment remain un-elucidated. Traditional herbal plants have been prescribed in many Asian countries for anti-aging and the modulation of aging-related symptoms. In general, herbal plants' efficacy is attributed to their safety and polypharmacological potency via the systemic manipulation of the body system. Radix polygalae (RP) is a herbal plant prescribed for anti-aging and the relief of age-related symptoms; however, its active components and biological functions remained un-elucidated. In this study, an active methanol fraction of RP containing 17 RP saponins (RPS), was identified. RPS attenuates the elevated C3 complement protein in aged mice to a level comparable to the young control mice. The active RPS also restates the aging gut microbiota by enhancing beneficial bacteria and suppressing harmful bacteria. In addition, RPS treatment improve spatial reference memory in aged mice, with the attenuation of multiple molecular markers related to neuroinflammation and aging. Finally, the RPS improves the behavior and extends the lifespan of C. elegans, confirming the herbal plant's anti-aging ability. In conclusion, through the mouse and C. elegas models, we have identified the beneficial RPS that can modulate the aging process, gut microbiota diversity and rectify several aging-related phenotypes.

Anti-hepatitis B virus activity of swertisin isolated from Iris tectorum Maxim.

ETHNOPHARMACOLOGICAL RELEVANCE: Iris tectorum Maxim (I. tectorum, Yuan Wei in Chinese) is a common and traditional Chinese medicinal herb that be used to treat liver-related diseases. However, the anti-HBV activity of I. tectorum and its isolates has not been systemically studied. AIM OF THE STUDY: To screen the active part of I. tectorum and systemically evaluate their anti-HBV activity. MATERIALS AND METHODS: In this study, a series of compounds from I. tectorum were evaluated for their ability to inhibit HBV replication. Swertisin showed a significant inhibitory function on HBV replication. Then, the suppression effect of different concentrations of swertisin in HBsAg, HBeAg and HBV DNA level in HepG2.2.15 cells and HBV-infected HepG2-NTCP cells were comprehensive evaluated, respectively. Moreover, the anti-HBV effects of swertisin were confirmed in HBV transgenic mice model. RESULTS: Among these compounds, swertisin strongly inhibited the HBsAg, HBeAg and HBV DNA level in a dose-dependent manner in HepG2.2.15 cells and HBV-infected HepG2-NTCP cells. Furthermore, swertisin showed a significant inhibition role on HBV replication in HBV transgenic mice model, the inhibition effect of which was enhanced when combined with ETV. CONCLUSIONS: We have identified that swertisin can inhibit HBeAg and HBsAg production, as well as HBV DNA in vitro and in vivo. This study show that we may found a novel compound isolated from traditional Chinese medicines with potent anti-HBV function.

Core-Shell Encapsulation of Lipophilic Substance in Jelly Fig (Ficus awkeotsang Makino) Polysaccharides Using an Inexpensive Acrylic-Based Millifluidic Device.

The polysaccharides extracted from the achenes of jelly fig, Ficus awkeotsang Makino, were mainly composed of low methyl pectin and used as a novel shell material for encapsulating lipophilic bioactives in the core of microcapsule. The polysaccharide microcapsules with oil core were prepared using a novel acrylic-based millifluidic device developed in this study. To investigate the physiochemical properties of and find the suitable formula of polysaccharide shells, the films casted with jelly fig polysaccharide were thoroughly characterized. For the preparation of microcapsules, the millifluidic device was optimized by controlling the flow rate to obtain uniform spherical shape with a core diameter of 1.4-1.9 mm and the outer diameter of 2.1-2.8 mm. The encapsulation efficiency was around 90%, and the microcapsules displayed a clear boundary between the polysaccharide shell and oil core. Encapsulation of curcumin in the microcapsules was prepared to test the applicability of the device and processes developed in this study, and the results showed that the microencapsulation could enhance the stability of curcumin against external environment. Overall, the results suggested that the jelly fig polysaccharides and the developed millifluidic device can be useful for the preparation of core-shell microcapsules for encapsulation of lipophilic bioactives.

Ammonium regulates Fe deficiency responses by enhancing nitric oxide signaling in Arabidopsis thaliana.

MAIN CONCLUSION: The accumulation of NH4+ in response to Fe deficiency plays a role not only in the remobilization of Fe from the root cell wall, but also in the transportation of Fe from root to shoot. Ammonium (NH4+) plays an important role in phosphorus-deficiency responses in rice, but its role in responses to Fe deficiency remains unknown. Here, we demonstrate that the accumulation of NH4+ plays a pivotal role when Arabidopsis thaliana plants are subject to Fe deficiency. The Arabidopsis amt1-3 mutant, which is defective in endogenous NH4+ sensing, exhibited increased sensitivity to Fe deficiency compared to WT (wild type; Col-0). In addition, exogenous application of NH4+ significantly alleviated Fe deficiency symptoms in plants. NH4+ triggers the production of nitric oxide (NO), which then induces ferric-chelate reductase (FCR) activity and accelerates the release of Fe from the cell wall, especially hemicellulose, thereby increasing the availability of soluble Fe in roots. NH4+ also increases soluble Fe levels in shoots by upregulating genes involved in Fe translocation, such as FRD3 (FERRIC REDUCTASE DEFECTIVE3) and NAS1 (NICOTIANAMINE SYNTHASE1), hence, alleviating leaf chlorosis. Overall, NH4+ plays an important role in the reutilization of Fe from the cell wall and the redistribution of Fe from root to shoot in Fe-deficient Arabidopsis, a process dependent on NO accumulation.

Effects of CytoReductive surgery plus hyperthermic IntraPEritoneal chemotherapy (HIPEC) versus CytoReductive surgery for ovarian cancer patients: A systematic review and meta-analysis.

BACKGROUND: The effects of Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) and CytoReductive Surgery (CRS) for ovarian cancer patients remain controversial. METHODS: A systematic review and meta-analysis was conducted using PubMed, Embase and Web of Science databases to investigate Overall Survival (OS), Disease Free Survival (DFS) and adverse effects between HIPEC and CRS group. RESULTS: In our overall analysis (13 studies), patients in the HIPEC group exhibited a significantly improved OS (HR = 0.56, 95% CI = 0.41-0.76, P < 0.01) and DFS (HR = 0.61, 95% CI = 0.48-0.77, P < 0.01). Subgroup analysis revealed improved OS (HR = 0.57, 95% CI = 0.40-0.83, P = 0.04) and DFS (HR = 0.61, 95% CI = 0.47-0.80, P < 0.01) for primary ovarian cancer in favour of HIPEC group. However, recurrent ovarian cancer patients who received HIPEC exhibited only significantly improved OS (HR = 0.48, 95% CI = 0.24-0.96, P < 0.01) but not DFS (HR = 0.59, 95% CI = 0.33-1.08, P = 0.09). In addition, both significantly improved OS and DFS were also observed in patients who received HIPEC in the subgroups based on the following factors: studies published before 2015, studies with ≥100 total patients, a single drug used for HIPEC, 90-min HIPEC duration and a regimen of CRS plus HIPEC followed by chemotherapy. Moreover systematically reviewed toxicity, morbidity, mortality and long-term outcomes were tolerable after HIPEC. CONCLUSIONS: The addition of HIPEC to CRS could significantly improve OS of ovarian cancer patients, albeit optimal drug regimen is not clear.

Two Genes Encoding a Bacterial-Type ATP-Binding Cassette Transporter are Implicated in Aluminum Tolerance in Buckwheat.

Buckwheat (Fagopyrum esculentum Moench) shows high tolerance to aluminum (Al) toxicity, but the molecular mechanisms underlying its high Al tolerance are poorly understood. Here, we functionally characterized two genes (FeSTAR1 and FeSTAR2), which encode a nucleotide-binding domain and a membrane domain, respectively, of a bacterial-type ATP-binding cassette (ABC) transporter. The expression of FeSTAR1 and FeSTAR2 was induced by Al in both roots and leaves with higher expression in the roots. Spatial and tissue-specific expression analysis showed that the Al-induced expression of these two genes was found in both the root tips and basal root regions with higher expression in the root outer cell layers. The expression was neither induced by other metals including Cd and La nor by low pH and phosphorus-deficiency. FeSTAR1 and FeSTAR2 were present in a single copy in the genome, but the Al-induced transcript copy number of FeSTAR1 and FeSTAR2 was much higher than their homologous genes in rice and Arabidopsis. FeSTAR1 and FeSTAR2 form a complex when co-expressed in onion epidermal cells. Introduction of FeSTAR1 and FeSTAR2 into Arabidopsis mutants atstar1 and als3/atstar2, respectively, rescued the sensitivity of the mutants to Al. Taken together, our results indicate that FeSTAR1 and FeSTAR2 are involved in Al tolerance and that their high expression level may contribute to high Al tolerance in buckwheat.

SIRT3 restricts hepatitis B virus transcription and replication through epigenetic regulation of covalently closed circular DNA involving suppressor of variegation 3-9 homolog 1 and SET domain containing 1A histone methyltransferases.

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA), which serves as a template for HBV RNA transcription, is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified silent mating type information regulation 2 homolog 3 (SIRT3) as a host factor restricting HBV transcription and replication by screening seven members of the sirtuin family, which is the class III histone deacetylase. Ectopic SIRT3 expression significantly reduced total HBV RNAs, 3.5-kb RNA, as well as replicative intermediate DNA in HBV-infected HepG2-Na+ /taurocholate cotransporting polypeptide cells and primary human hepatocytes. In contrast, gene silencing of SIRT3 promoted HBV transcription and replication. A mechanistic study found that nuclear SIRT3 was recruited to the HBV cccDNA, where it deacetylated histone 3 lysine 9. Importantly, occupancy of SIRT3 on cccDNA could increase the recruitment of histone methyltransferase suppressor of variegation 3-9 homolog 1 to cccDNA and decrease recruitment of SET domain containing 1A, leading to a marked increase of trimethyl-histone H3 (Lys9) and a decrease of trimethyl-histone H3 (Lys4) on cccDNA. Moreover, SIRT3-mediated HBV cccDNA transcriptional repression involved decreased binding of host RNA polymerase II and transcription factor Yin Yang 1 to cccDNA. Finally, hepatitis B viral X protein could relieve SIRT3-mediated cccDNA transcriptional repression by inhibiting both SIRT3 expression and its recruitment to cccDNA. CONCLUSION: SIRT3 is a host factor epigenetically restricting HBV cccDNA transcription by acting cooperatively with histone methyltransferase; these data provide a rationale for the use of SIRT3 activators in the prevention or treatment of HBV infection. (Hepatology 2018).

Nitrate inhibits the remobilization of cell wall phosphorus under phosphorus-starvation conditions in rice (Oryza sativa).

MAIN CONCLUSION: NO3- not only inhibited the reutilization of cell wall P via decreasing root cell wall pectin content and PME activity, but also hampered the P translocation from root to shoot. The rice cultivars 'Kasalath' (Kas) and 'Nipponbare' (Nip) were used to demonstrate that the nitrogen source NO3- inhibits internal phosphorus (P) reutilization in rice under P-absence conditions. Analysis using Kas showed that the expression of - P-induced marker genes OsIPS1/2 and OsSPX1/2/3/5 are significantly higher under 1 mM NO 3- - P (1N - P) treatment than 0 mM NO 3- - P (0N - P) treatment. The absence of NO3- from the nutrient solution significantly increased cell wall P release by increasing pectin synthesis and increasing the activity of pectin methylesterase (PME), and also significantly improved the translocation of soluble P from the root to the shoot by increasing xylem sap P content under P-absence conditions. The rice seedlings grown in 0 mM NO3- accumulated significantly higher nitric oxide (NO) in the roots than those grown in 1 mM NO3-. Exogenously applying the NO donor sodium nitroprusside (SNP) revealed that NO is a major contributor to differential cell wall P remobilization in rice by mediating pectin synthesis and demethylation under different NO3- concentrations (0 and 1 mM) under P-deprived conditions.

Systematic Review on Effects of Acupuncture Combined with Lifestyle Modification on Essential Hypertension / 中国中医药信息杂志

Objective To evaluate the effects of acupuncture combined with lifestyle modification for essential hypertension by Meta-analysis. Methods Clinical randomized controlled trial literature about acupuncture combined with lifestyle modification for essential hypertension in CNKI, WanFang Data, CBM, VIP, PubMed, Embase, and Web of Science since establishment to February 20, 2017 were retrieved. Data extraction and quality assessment of studies were conducted by two researchers independently, and the Meta-analysis was performed by the software of RevMan5.3. Results 5 articles involving 467 patients were included. The results of Meta-analysis showed that acupuncture combined with lifestyle modification had more significant effect than lifestyle modification alone in lowing SBP [SMD=-1.52(-2.40,-0.64)], in lowing DBP [SMD=-1.02(-2.01,-0.03)], total effective rates [RR=1.27(1.13, 1.43)]. Conclusion Compared with lifestyle modification alone, acupuncture combined with lifestyle modification have significant effects for patients with essential hypertension, but because of the fewer studies included, bigger heterogeneity between studies and the lower quality of included studies still exist, the results should be further verified, and clinical applications should be treated with caution.

PARVUS affects aluminium sensitivity by modulating the structure of glucuronoxylan in Arabidopsis thaliana.

Glucuronoxylan (GX), an important component of hemicellulose in the cell wall, appears to affect aluminium (Al) sensitivity in plants. To investigate the role of GX in cell-wall-localized xylan, we examined the Arabidopsis thaliana parvus mutant in detail. This mutant lacks α-D-glucuronic acid (GlcA) side chains in GX and has greater resistance to Al stress than wild-type (WT) plants. The parvus mutant accumulated lower levels of Al in its roots and cell walls than WT despite having cell wall pectin content and pectin methylesterase (PME) activity similar to those of WT. Our results suggest that the altered properties of hemicellulose in the mutant contribute to its decreased Al accumulation. Although we observed almost no differences in hemicellulose content between parvus and WT under control conditions, less Al was retained in parvus hemicellulose than in WT. This observation is consistent with the finding that GlcA substitutions in WT GX, but not mutant GX, were increased under Al stress. Taken together, these results suggest that the modulation of GlcA levels in GX affects Al resistance by influencing the Al binding capacity of the root cell wall in Arabidopsis.

Nitric oxide acts upstream of ethylene in cell wall phosphorus reutilization in phosphorus-deficient rice.

Nitric oxide (NO) and ethylene are both involved in cell wall phosphorus (P) reutilization in P-deficient rice; however, the crosstalk between them remains unclear. In the present study using P-deficient 'Nipponbare' (Nip), root NO accumulation significantly increased after 1 h and reached a maximum at 3 h, while ethylene production significantly increased after 3 h and reached a maximum at 6 h, indicating NO responded more quickly than ethylene. Irrespective of P status, addition of the NO donor sodium nitroprusside (SNP) significantly increased while the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) significantly decreased the production of ethylene, while neither the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) nor the ethylene inhibitor aminoethoxyvinylglycine (AVG) had any influence on NO accumulation, suggesting NO acted upstream of ethylene. Under P-deficient conditions, SNP and ACC alone significantly increased root soluble P content through increasing pectin content, and c-PTIO addition to the ACC treatment still showed the same tendency; however, AVG+SNP treatment had no effect, further indicating that ethylene was the downstream signal affecting pectin content. The expression of the phosphate transporter gene OsPT2 showed the same tendency as the NO-ethylene-pectin pathway. Taken together, we conclude that ethylene functions downstream of NO in cell wall P reutilization in P-deficient rice.