Soybean-mediated suppression of BjaI/BjaR1 quorum sensing in Bradyrhizobium diazoefficiens impacts symbiotic nitrogen fixation.

The acyl-homoserine lactones (AHLs)-mediated LuxI/LuxR quorum sensing (QS) system orchestrates diverse bacterial behaviors in response to changes in population density. The role of the BjaI/BjaR1 QS system in Bradyrhizobium diazoefficiens USDA 110, which shares homology with LuxI/LuxR, remains elusive during symbiotic interaction with soybean. Here this genetic system in wild-type (WT) bacteria residing inside nodules exhibited significantly reduced activity compared to free-living cells, potentially attributed to soybean-mediated suppression. The deletion mutant strain ΔbjaR1 showed significantly enhanced nodulation induction and nitrogen fixation ability. Nevertheless, its ultimate symbiotic outcome (plant dry weight) in soybeans was compromised. Furthermore, comparative analysis of the transcriptome, proteome, and promoter activity revealed that the inactivation of BjaR1 systematically activated and inhibited genomic modules associated with nodulation and nitrogen metabolism. The former appeared to be linked to a significant decrease in the expression of NodD2, a key cell-density-dependent repressor of nodulation genes, while the latter conferred bacterial growth and nitrogen fixation insensitivity to environmental nitrogen. In addition, BjaR1 exerted a positive influence on the transcription of multiple genes involved in a so-called central intermediate metabolism within the nodule. In conclusion, our findings highlight the crucial role of the BjaI/BjaR1 QS circuit in positively regulating bacterial nitrogen metabolism and emphasize the significance of the soybean-mediated suppression of this genetic system for promoting efficient symbiotic nitrogen fixation by B. diazoefficiens.IMPORTANCEThe present study demonstrates, for the first time, that the BjaI/BjaR1 QS system of Bradyrhizobium diazoefficiens has a significant impact on its nodulation and nitrogen fixation capability in soybean by positively regulating NodD2 expression and bacterial nitrogen metabolism. Moreover, it provides novel insights into the importance of suppressing the activity of this QS circuit by the soybean host plant in establishing an efficient mutual relationship between the two symbiotic partners. This research expands our understanding of legumes' role in modulating symbiotic nitrogen fixation through rhizobial QS-mediated metabolic functioning, thereby deepening our comprehension of symbiotic coevolution theory. In addition, these findings may hold great promise for developing quorum quenching technology in agriculture.

Telephone instructions improve the quality of bowel preparation for colonoscopy: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effect of telephone instructions on the quality of bowel preparation in patients undergoing colonoscopy. METHODS: Online English databases (PubMed, Web of Science, Cochrane Library, and Embase) were screened for randomized controlled trials on telephone instructions regarding bowel preparation for colonoscopy from inception to April 15, 2022. After data extraction, the Review Manager software was used for meta-analysis. RESULTS: Nine randomized controlled trials with 3,836 patients were included in the meta-analysis. The rate of adequate bowel preparation was significantly higher in the telephone group than in the control group. The pooled relative risk (RR) was 1.17 (95% confidence interval [CI]: 1.05-1.30, P < 0.01). The pooled mean difference (MD) for the Boston Bowel Preparation Scale score was 1.32 (95% CI: 0.15-2.49, P < 0.05), and that for the Ottawa Bowel Preparation Scale score was -1.93 (95% CI: -2.35 to -1.51, P < 0.01). The polyp detection rate was significantly higher in the telephone group than in the control group (RR = 1.58, 95% CI: 1.23-2.04, P < 0.01), whereas no significant difference was noted in the adenoma detection rate between the groups (RR = 1.37, 95% CI: 0.97-1.94, P = 0.08). CONCLUSION: Telephone instructions for patients undergoing colonoscopy significantly improved the quality of bowel preparation and increased polyp detection rate.

Aniline-induced production of aniline-containing polyketides and related bicyclic polyketides by the Yellow River wetland-derived fungus Talaromyces funiculosus.

Introduction and Methods: Silencing gene activation can effectively enrich the diversity of fungal secondary metabolites. Results and Discussion: Cultivation of the Yellow River wetland-derived fungus Talaromyces funiculosus HPU-Y01 with aniline led to the isolation of one new aniline-containing polyketide tanicutone A (1), two new bicyclic polyketides tanicutones B-C (2-3), a new related trienoic acid 8-methyldeca-2,4,6-trienoic acid (5), and a known compound 4. The planar structures and configurations of 1-5 were determined by NMR, MS, and ECD calculations. Compound 2 featured a key aldehyde group and showed promising inhibitory activity against Vibrio parahaemolyticus with a minimum inhibitory concentration (MIC) value of 0.17 µg/mL. This is a rare report of aniline-induced fungal production of tetrahydronaphthone polyketides.

Stress response and influencing factors among fever outpatients and children's families during normalisation of the COVID-19 epidemic: A cross-sectional study.

AIM: To examine the demographic characteristics associated with stress response of fever outpatients and children's families during normalisation of the COVID-19 epidemic and to examine the relationship between stress response, coping style and resilience. DESIGN: Online cross-sectional study. METHODS: A total of 541 fever clinic participants from Yiwu, China, were recruited via WeChat from February to November 2021. Online self-administered questionnaires were used to collect data. Data were analysed using t-tests, one-way analyses of variance, Pearson's correlation analyses and multiple linear regression analyses. RESULTS: There were apparent physical and emotional responses among the fever outpatients, especially the adult patients. The main coping style was negative coping, and the degree of psychological resilience was low. Income, comorbidities, religious beliefs, tenacity, negative coping and positive coping were independent predictors of stress response.

Production of Multiple Talaroenamines from Penicillium malacosphaerulum via One-Pot/Two-Stage Precursor-Directed Biosynthesis.

Nineteen new talaroenamine derivatives, talaroenamines F1-F19 (1-19), were isolated from the Yellow River wetland derived Penicillium malacosphaerulum HPU-J01 by use of a one-pot/two-stage precursor-directed biosynthesis approach. During this approach, the initial precursor p-methylaniline was first used as a carrier to capture the biologically synthesized cyclohexanedione to produce talaroenamine F, and then the other aniline derivatives were employed to replace the p-methylaniline fragment of talaroenamine F to generate the final products. LC-MS analysis showed that only four compounds (2, 8, 10, and 12) could be produced by the traditional precursor-directed biosynthesis in which the aniline precursors were added simultaneously. Compound 14 was cytotoxic against the K562 cell line with an IC50 value of 2.2 µM. This work demonstrated the one-pot/two-stage precursor-directed biosynthesis could improve substrate acceptance leading to the production of diverse talaroenamines.

Patient education by smartphones for bowel preparation before colonoscopy.

BACKGROUND AND AIM: We aim to evaluate the effect of smartphone education on the bowel preparation quality of patients undergoing colonoscopy by meta-analysis. METHODS: Randomized controlled trials using smartphones to educate patients on bowel preparation for colonoscopy were screened from the PubMed, Web of Science, Cochrane Library, and Embase databases from inception to August 31, 2021. After extracting the data, Review Manager software was used for meta-analysis. RESULTS: A total of 12 randomized controlled trials with 4165 patients were included in the meta-analysis. There were 2060 patients in the smartphone group, including 1784 patients with adequate bowel preparation, with a rate of 86.6%, and 2105 patients in the control group, including 1614 patients with adequate bowel preparation, with a rate of 76.7%, and pooled risk ratio (RR) was 1.15 (95% confidence interval [CI]: 1.07-1.23, P < 0.01). Eight included studies reported the adenoma detection rate. The adenoma detection rate in the smartphone group was 26.2%, and the rate in the control group was 19.3%, with an RR of 1.29 (95% CI: 1.03-1.62, P < 0.05). CONCLUSION: Using smartphones to educate patients on bowel preparation for colonoscopy improved the quality of bowel preparation and increased the adenoma detection rate.

Impact of Patient Education via WeChat on Bowel Preparation for Colonoscopy: A Meta-analysis of Randomized Controlled Trials.

The aim of this study was to evaluate the impact of education via WeChat on the quality of bowel preparation in patients undergoing colonoscopy through a meta-analysis of randomized controlled trials. Randomized controlled trials of bowel preparation education provided via WeChat for patients undergoing colonoscopy were screened from databases such as PubMed, Web of Science, Cochrane Library, and Embase. Papers published from the date of database construction to May 1, 2021, were extracted, and a meta-analysis was performed using Review Manager software. A total of four randomized controlled trials were included in the meta-analysis. The results showed that for patients undergoing colonoscopy, education via WeChat significantly improves the quality of bowel preparation for colonoscopy, reduces the insertion time, and increases the adenoma detection rate and the patient's compliance and willingness to repeat bowel preparation. In conclusion, education via WeChat before colonoscopy can significantly improve the quality of bowel preparation.

Reinforced education by short message service improves the quality of bowel preparation for colonoscopy.

PURPOSE: This study aimed to evaluate the effect of reinforced education (RE) by short message service (SMS) on the bowel preparation quality of patients undergoing colonoscopy. METHODS: Randomized controlled trials (RCTs), conducted on the effect of RE by SMS on bowel preparation for colonoscopy from inception to November 1, 2021, were queried from databases, including PubMed, Web of Science, the Cochrane Library, and EMBASE. After extracting the data, meta-analysis was conducted using Review Manager Software version 5.3. RESULTS: A total of seven RCTs with 5889 patients were subjected to meta-analysis. The rate of adequate bowel preparation in the SMS group (81.7%) was significantly higher than that in the control group (75.7%) (RR: 1.10, 95% CI: 1.03-1.17, p < 0.01). Four studies suggested that RE by SMS significantly reduced the non-attendance rate of patients for scheduled colonoscopy (RR: 0.74, 95% CI: 0.56-0.99, p < 0.05). CONCLUSION: RE by SMS for patients undergoing colonoscopy can significantly improve the quality of bowel preparation and decrease the non-attendance rate of patients for scheduled colonoscopy.

Precursor-Directed Biosynthesis of Talaroenamine Derivatives Using a Yellow River Wetland-Derived Penicillium malacosphaerulum.

Precursor-directed biosynthesis was used to introduce selected aniline derivatives into the talaroenamine pathway, which had recently been defined from a Yellow River wetland-derived Penicillim malacosphaerulum HPU-J01. The known talaroenamine B (1) and six previously undescribed talaroenamine derivatives, talaroenamines F-K (2-7), were generated and structurally characterized. The aniline derivatives are introduced via nonenzymatic addition to the reactive intermediate cyclohexanedione. Compound 2 was active against Bacillus cereus with an MIC value of 0.85 µg/mL.

Involvement of a Novel TetR-Like Regulator (BdtR) of Bradyrhizobium diazoefficiens in the Efflux of Isoflavonoid Genistein.

A wide variety of leguminous plant-released (iso)flavonoids, such as genistein, are potential inducers of the nodulation (nod) genes of endosymbiotic rhizobia for the production of Nod factors, which are vital signaling molecules for triggering the symbiotic process. However, these (iso)flavonoids are generally thought to be toxic to the bacterial partner to varying degrees. Here, a novel TetR-like regulator gene of the soybean symbiont Bradyrhizobium diazoefficiens USDA110, bdtR (systematic designation blr7023), was characterized. It was found to be rapidly and preferentially induced by genistein, and its mutation resulted in significantly increased expression of the neighboring bll7019-bll7021 genes, encoding a multidrug resistance efflux pump system, in the absence of this isoflavonoid. Then, the transcriptional start site of BdtR was determined, and it was revealed that BdtR acted as a transcriptional repressor of the above efflux system through the binding of an AT-rich operator, which could be completely prevented by genistein. In addition, the ΔbdtR deletion mutant strain showed higher accumulation of extracellular genistein and became less susceptible to the isoflavonoid. In contrast, the inactivation of BdtR led to the significantly decreased induction of a nodulation gene (nodY) independent of the expression of nodD1 and nodW and to much weaker nodulation competitiveness. Taken together, the results show that BdtR plays an early sensing role in maintaining the intracellular homeostasis of genistein, helping to alleviate its toxic effect on this bacterium by negatively regulating neighboring genes encoding an efflux pump system while being essentially required for nodule occupancy competitiveness.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

A meta-analysis of randomized controlled trials of the addition of lubiprostone to bowel preparation before colonoscopy.

AIM: Adequate bowel preparation is essential to the quality of colonoscopy. We performed a meta-analysis to determine the efficacy and safety of the addition of lubiprostone to the bowel preparation process prior to colonoscopy. METHODS: Online databases, namely, PubMed, MEDLINE and Cochrane Library, were searched for randomized controlled trials that assessed the additive effect of lubiprostone on the quality of colon preparation in patients undergoing colonoscopy. Each included study was evaluated by the Jadad score to assess the quality of the study. The primary outcome was bowel preparation efficacy, defined as the proportion of patients with an excellent or poor preparation. The secondary outcomes included the length of the colonoscopy, polyp detection, and any adverse effects. RESULTS: In total, 5 articles published between 2008 and 2016 fulfilled the selection criteria. The addition of lubiprostone to the bowel cleansing process significantly increased the proportion of patients with an excellent preparation (risk ratio [RR] = 1.68, 95% confidence interval (CI): 1.40-2.02, P < .00001) but did not decrease the procedural time or increase the polyp detection rate (mean difference = -0.52, 95% CI: -3.74-2.69, P = .75; RR = 1.16, 95% CI: 0.96-1.42, P = .13, respectively). There was no significant difference in the proportion of patients with any adverse events. CONCLUSION: The addition of lubiprostone to the bowel preparation regimen prior to colonoscopy is effective and safe.

Correction to: Varilactones and wortmannilactones produced by Penicillium variabile cultured with histone deacetylase inhibitor.

The author would like to include conflict of interest statement of the online published article. The correct conflict of interest statement should read as.

Aniline-Tetramic Acids from the Deep-Sea-Derived Fungus Cladosporium sphaerospermum L3P3 Cultured with the HDAC Inhibitor SAHA.

Four new tetramic acids, cladosins H-K (1-4), and a related known compound, cladodionen (5), were isolated from the culture of the Mariana Trench (depth 6562 m) sediment-derived fungus Cladosporium sphaerospermum L3P3 treated with the histone deacetylase inhibitor SAHA (suberanilohydroxamic acid). Interestingly, compounds 1-5 existed as equilibrium E/ Z mixtures and 1-4 were the first cases of tetramic acids containing aniline moieties. Their structures including absolute configurations were elucidated through a combination of NMR, MS, and Mosher's method, together with the consideration of biogenetic origins. Incubation experiments of exogenous aniline and N-phenyloctanamide revealed that the aniline moiety in cladosins H-K (1-4) is probably derived from the degradation of SAHA, indicating that the well-known histone deacetylase inhibitor SAHA could be metabolized by L3P3 and provide aniline as a precursor for biotransformation of chemically reactive polyketides. The cytotoxicity of 1-5 was evaluated against the PC-3, MGC-803, SH-SY5Y, HCT-116, K562, and HL-60 cell lines, and compound 2 showed promising cytotoxicity against the HL-60 cell line with an IC50 value of 2.8 µM.

Sorbicillasins A⁻B and Scirpyrone K from a Deep-Sea-Derived Fungus, Phialocephala sp. FL30r.

Two new nitrogen-containing sorbicillinoids named sorbicillasins A and B (1 and 2) and a new 3,4,6-trisubstituted α-pyrone derivative, scirpyrone K (3), together with two known biosynthetically related polyketides (4⁻5), were isolated from the deep-sea-derived fungus Phialocephala sp. FL30r by using the OSMAC (one strain-many compounds) method. The structures of 1⁻3, including absolute configurations, were deduced based on MS, NMR, and time-dependent density functional theory (TD-DFT) calculations of specific ECD (electronic circular dichroism) spectra. Compounds 1 and 2 possessed a novel hexahydropyrimido[2,1-a] isoindole moiety, and compound 3 exhibited weak radical scavenging activity against DPPH (2,2-diphenyl-1-picrylhydrazyl) with an IC50 value of 27.9 µM.

Varilactones and wortmannilactones produced by Penicillium variabile cultured with histone deacetylase inhibitor.

Seven polyketides, including four new ones named as varilactones A-B (1-2) and wortmannilactones M-N (3-4), as well as three biogenetically related known wortmannilactones E, F and H (5-7), were isolated from the fungus Penicillium variabile HXQ-H-1, cultivated in potato-based medium with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Their structures (1-7) were established by analysis of NMR and MS data, and the absolute configuration of oxabicyclo[2.2.1]heptane unit was deduced from 1H-NMR analyses on MPA esters after chemical reduction reaction. Among them, varilactones A and B (1 and 2), features a novel skeleton with a triene unit linking an oxabicyclo[2.2.1]heptane and an oxabicyclo[3.3.0]octane rings.

Inducing Secondary Metabolite Production by Combined Culture of Talaromyces aculeatus and Penicillium variabile.

Four new polyketides, penitalarins A-C (1-3) and nafuredin B (4), together with the known biogenetically related nafuredin A (5) were isolated from a mixed culture of a deep-sea-derived fungus Talaromyces aculeatus and a mangrove-derived fungus Penicillium variabile. Liquid chromatography/mass spectrometry analysis showed that none of compounds 1-5 was produced by either of the two fungi when cultured alone under the same condition. The structures of 1-4, including absolute configurations, were deduced based on the interpretation of MS, NMR data, and time-dependent density functional theory calculations of specific electronic circular dichroism spectra. Compounds 1-3 possess a 3,6-dioxabicyclo[3.1.0]hexane ring, and 4 showed cytotoxicity with IC50 values ranging from 1.2 to 9.8 µM against a panel of human cancer cell lines.

Late-Stage Terpene Cyclization by an Integral Membrane Cyclase in the Biosynthesis of Isoprenoid Epoxycyclohexenone Natural Products.

Macrophorins are representative examples of isoprenoid epoxycyclohexenones containing cyclized drimane moieties. We located and characterized the biosynthetic gene cluster of macrophorin from Penicillium terrestris. MacJ encoded by this cluster was characterized to be the first example of a membrane-bound type-II terpene cyclase catalyzing the cyclization of meroterpenoids via direct protonation of the terminal olefinic bond in acyclic yanuthones. The late-stage functionalization and substrate promiscuity of MacJ make it a potential biocatalyst for the synthesis of macrophorin analogues.

Peniphenylanes A-G from the Deep-Sea-Derived Fungus Penicillium fellutanum HDN14-323.

Seven new 6-methylsaligenin derivatives, including the trimeric peniphenylanes A-B (1-2) and dimeric peniphenylanes C-G (3-7), together with four known biogenetically related compounds (8-11) were discovered from the extract of the deep-sea-derived fungus Penicillium fellutanum HDN14-323. The structures of the new compounds were established through extensive analysis. Their cytotoxic activity against HeLa, HL-60, and HCT-116 cell lines was evaluated, with compound 4 exhibiting the best activity against the HeLa cell line (IC50 = 9.3 µM).

Varitatin A, a Highly Modified Fatty Acid Amide from Penicillium variabile Cultured with a DNA Methyltransferase Inhibitor.

A new, highly modified fatty acid amide, varitatin A (1), was isolated from the fungus Penicillium variabile HXQ-H-1 cultivated with the DNA methyltransferase inhibitor 5-azacytidine. The structure including the absolute configuration of 1 was established by analysis of NMR and MS data, together with chemical degradation and Mosher's method based on MPA esters. Compound 1 showed cytotoxicity against HCT-116 cells with an IC50 value of 2.8 µM and also inhibited the effects of protein tyrosine kinases.