Biosynthesis of Putrescine from L-arginine Using Engineered Escherichia coli Whole Cells

Putrescine, a biogenic amine, is a highly valued compound in medicine, industry, and agriculture. In this study, we report a whole-cell biocatalytic method in Escherichia coli for the production of putrescine, using L-arginine as the substrate. L-arginine decarboxylase and agmatine ureohydrolase were co-expressed to produce putrescine from L-arginine. Ten plasmids with different copy numbers and ordering of genes were constructed to balance the expression of the two enzymes, and the best strain was pACYCDuet-speB-speA. The optimal concentration of L-arginine was determined to be 20 mM for this strain. The optimum pH of the biotransformation was 9.5, and the optimum temperature was 45 °C; under these conditions, the yield of putrescine was 98%. This whole-cell biocatalytic method appeared to have great potential for the production of putrescine.</jats:p

Anticonvulsant activities of α-asaronol ((E)-3'-hydroxyasarone), an active constituent derived from α-asarone.

BACKGROUND: Epilepsy is one of chronic neurological disorders that affects 0.5-1.0% of the world's population during their lifetime. There is a still significant need to develop novel anticonvulsant drugs that possess superior efficacy, broad spectrum of activities and good safety profile. METHODS: α-Asaronol and two current antiseizure drugs (α-asarone and carbamazepine (CBZ)) were assessed by in vivo anticonvulsant screening with the three most employed standard animal seizure models, including maximal electroshock seizure (MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3-mercaptopropionic acid (3-MP)-induced seizures in mice. Considering drug safety evaluation, acute neurotoxicity was assessed with minimal motor impairment screening determined in the rotarod test, and acute toxicity was also detected in mice. RESULTS: In our results, α-asaronol displayed a broad spectrum of anticonvulsant activity (ACA) and showed better protective indexes (PI = 11.11 in MES, PI = 8.68 in PTZ) and lower acute toxicity (LD50 = 2940 mg/kg) than its metabolic parent compound (α-asarone). Additionally, α-asaronol displayed a prominent anticonvulsant profile with ED50 values of 62.02 mg/kg in the MES and 79.45 mg/kg in the sc-PTZ screen as compared with stiripentol of ED50 of 240 mg/kg and 115 mg/kg in the relevant test, respectively. CONCLUSION: The results of the present study revealed α-asaronol can be developed as a novel molecular in the search for safer and efficient anticonvulsants having neuroprotective effects as well as low toxicity. Meanwhile, the results also suggested that α-asaronol has great potential to develop into another new aromatic allylic alcohols type anticonvulsant drug for add-on therapy of Dravet's syndrome

Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets

Mitochondria are the centrol hub for cellular energy metabolisms. They regulate fuel metabolism by oxygen levels, participate in physiological signaling pathways, and act as oxygen sensors. Once oxygen deprived, the fuel utilizations can be switched from mitochondrial oxidative phosphorylation to glycolysis for ATP production. Notably, mitochondria can also adapt to hypoxia by making various functional and phenotypes changes to meet the demanding of oxygen levels. Hypoxic pulmonary hypertension is a life-threatening disease, but its exact pathgenesis mechanism is still unclear and there is no effective treatment available until now. Ample of evidence indicated that mitochondria play key factor in the development of hypoxic pulmonary hypertension. By hypoxia-inducible factors, multiple cells sense and transmit hypoxia signals, which then control the expression of various metabolic genes. This activation of hypoxia-inducible factors considered associations with crosstalk between hypoxia and altered mitochondrial metabolism, which plays an important role in the development of hypoxic pulmonary hypertension. Here, we review the molecular mechanisms of how hypoxia affects mitochondrial function, including mitochondrial biosynthesis, reactive oxygen homeostasis, and mitochondrial dynamics, to explore the potential of improving mitochondrial function as a strategy for treating hypoxic pulmonary hypertension

Homocysteine levels in first-episode patients with psychiatric disorders

A high homocysteine (Hcy) level is a risk factor for schizophrenia, depression, and bipolar disorder. However, the role of hyperhomocysteinemia as either an independent factor or an auxiliary contributor to specific psychiatric symptoms or disorders remains unclear. This study aimed to examine Hcy levels in first-episode inpatients with psychotic symptoms and various psychiatric diseases to elucidate the association between Hcy levels and psychiatric disorders. This study enrolled 191 patients (aged 18–40 years) with psychiatric disorders. Seventy-five patients were diagnosed with schizophrenia, 48 with acute and transient psychotic disorders, 36 with manic episodes with psychosis, 32 with major depressive episodes with psychosis, and 56 healthy controls. Serum Hcy levels were measured using the enzyme cycle method. A Hcy concentration level of &gt; 15 μmol/L was defined as hyperhomocysteinemia. Hcy levels were significantly higher in first-episode patients with psychiatric disorders compared to healthy controls (5.99 ± 3.60 vs. 19.78 ± 16.61 vs. 15.50 ± 9.08 vs. 20.00 ± 11.33 vs. 16.22 ± 12.06, F = 12.778, P &lt; 0.001). Hcy levels were significantly higher in males with schizophrenia, acute and transient psychotic disorder, and major depressive disorder but not in mania [schizophrenia, (t = -4.727, P &lt; 0.001); acute and transient psychotic disorders, (t = -3.389, P = 0.001); major depressive episode with psychosis, (t = -3.796, P &lt; 0.001); manic episodes with psychosis, (t = -1.684, P = 0.101)]. However, serum Hcy levels were not significantly different among the psychiatric disorder groups (F = 0.139, P = 0.968). Multivariate linear regression showed that males had an increased risk for homocysteinemia. (95% CI = 8.192–15.370, P &lt; 0.001). These results suggest that first-episode patients with psychiatric disorders have higher Hcy levels than in the general population, and men are at greater risk for psychiatric disorders. In conclusion, elevated Hcy levels may contribute to the pathogenesis of first-episode patients with psychotic symptoms

Assessing the Quality of Reports about Randomized Controlled Trials of Acupuncture Treatment on Diabetic Peripheral Neuropathy

BACKGROUND: To evaluate the reports' qualities which are about randomized controlled trials (RCTs) of acupuncture treatment on Diabetic Peripheral Neuropathy (DPN). METHODOLOGY/PRINCIPAL FINDINGS: Eight databases including The Cochrane Library(1993-Sept.,2011), PubMed (1980-Sept., 2011), EMbase (1980-Sept.,2011), SCI Expanded (1998-Sept.,2011), China Biomedicine Database Disc (CBMdisc, 1978-Sept., 2011), China National Knowledge Infrastructure (CNKI, 1979-Sept., 2011 ), VIP (a full text issues database of China, 1989-Sept., 2011), Wan Fang (another full text issues database of China 1998-Sept., 2011) were searched systematically. Hand search for further references was conducted. Language was limited to Chinese and English. We identified 75 RCTs that used acupuncture as an intervention and assessed the quality of these reports with the Consolidated Standards for Reporting of Trials statement 2010 (CONSORT2010) and Standards for Reporting Interventions Controlled Trials of Acupuncture 2010(STRICTA2010). 24 articles (32%) applied the method of random allocation of sequences. No article gave the description of the mechanism of allocation concealment, no experiment applied the method of blinding. Only one article (1.47%) could be identified directly from its title as about the Randomized Controlled Trials, and only 4 articles gave description of the experimental design. No article mentioned the number of cases lost or eliminated. During one experiment, acupuncture syncope led to temporal interruption of the therapy. Two articles (2.94%) recorded the number of needles, and 8 articles (11.76%) mentioned the depth of needle insertion. None of articles reported the base of calculation of sample size, or has any analysis about the metaphase of an experiment or an explanation of its interruption. One (1.47%) mentioned intentional analysis (ITT). CONCLUSIONS/SIGNIFICANCE: The quality of the reports on RCTs of acupuncture for Diabetic Peripheral Neuropathy is moderate to low. The CONSORT2010 and STRICTA2010 should be used to standardize the reporting of RCTs of acupuncture in future

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake