Hydroxytyrosol is an antioxidant free radical scavenger that is biosynthesized from tyrosine. In metabolic engineering efforts, the use of the mouse tyrosine hydroxylase limits its production. Here, ...we design an efficient whole-cell catalyst of hydroxytyrosol in Escherichia coli by de-bottlenecking two rate-limiting enzymatic steps. First, we replace the mouse tyrosine hydroxylase by an engineered two-component flavin-dependent monooxygenase HpaBC of E. coli through structure-guided modeling and directed evolution. Next, we elucidate the structure of the Corynebacterium glutamicum VanR regulatory protein complexed with its inducer vanillic acid. By switching its induction specificity from vanillic acid to hydroxytyrosol, VanR is engineered into a hydroxytyrosol biosensor. Then, with this biosensor, we use in vivo-directed evolution to optimize the activity of tyramine oxidase (TYO), the second rate-limiting enzyme in hydroxytyrosol biosynthesis. The final strain reaches a 95% conversion rate of tyrosine. This study demonstrates the effectiveness of sequentially de-bottlenecking rate-limiting steps for whole-cell catalyst development.
An electrical-thermal co-simulation based on the finite element method is presented for analysis of high-power RF/microwave circuits. The co-simulation integrates a full-wave electromagnetic analysis ...and a transient thermal analysis through an iterative scheme, and is devised for the design and analysis of RF/microwave circuits operated at high frequencies and high power levels. To enhance the efficiency in solving large-scale problems, a domain decomposition scheme called the finite element tearing and interconnecting and an adaptive time-stepping scheme based on the algorithm of proportional-integral-derivative control are incorporated into the co-simulation. Temperature stability analysis is performed with the proposed co-simulation for a matching network in high-power RF amplifiers and for a substrate integrated waveguide filter.
Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected ...patients.
We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death.
The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.
During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).
A modeling of metasurfaces in the finite-element method (FEM) based on generalized sheet transition conditions (GSTCs) is presented. The discontinuities in electromagnetic fields across a metasurface ...as represented by the GSTC are modeled by assigning nodes to both the sides of the metasurface. The FEM-GSTC formulation in both 1-D and 2-D domains is derived and implemented. The method is extended to handle more general bianistroptic metasurfaces. The formulations are validated by several illustrative examples.
Genetic diversity is a result of evolution, enabling multiple ways for one particular physiological activity. Here, we introduce this strategy into bioengineering. We design two hydroxytyrosol ...biosynthetic pathways using tyrosine as substrate. We show that the synthetic capacity is significantly improved when two pathways work simultaneously comparing to each individual pathway. Next, we engineer flavin-dependent monooxygenase HpaBC for tyrosol hydroxylase, tyramine hydroxylase, and promiscuous hydroxylase active on both tyrosol and tyramine using directed divergent evolution strategy. Then, the mutant HpaBCs are employed to catalyze two missing steps in the hydroxytyrosol biosynthetic pathways designed above. Our results demonstrate that the promiscuous tyrosol/tyramine hydroxylase can minimize the cell metabolic burden induced by protein overexpression and allow the biosynthetic carbon flow to be divided between two pathways. Thus, the efficiency of the hydroxytyrosol biosynthesis is significantly improved by rearranging the metabolic flux among multiple pathways.
Purpose
Probiotics have been reported to be beneficial for inflammatory bowel disease (IBD), but the types, number of strains, dosage, and intervention time of probiotics used remain controversial. ...Furthermore, the changes of gut microbiota in IBD’s patients are also intriguing. Thus, this meta-analysis was to explore the clinical effects and gut microbiota changes of using probiotics, prebiotics and synbiotics in IBD.
Methods
The search was performed in PubMed, Web of Science and the Cochrane library from inception to April 2020. Qualified randomized controlled trials were included. IBD’s remission rate, disease activity index and recurrence rate were extracted and analyzed. Changes in the gut microbiota of patients with IBD are comprehensively described.
Results
Thirty-eight articles were included. Probiotics, prebiotics and synbiotics can induce/maintain IBD’s remission and reduce ulcerative colitis (UC) disease activity index (RR = 1.13, 95% CI 1.02, 1.26,
P
< 0.05; SMD = 1.00, 95% CI 0.27, 1.73,
P
< 0.05). In subgroup analyses of IBD remission rate and UC disease activity index, we obtained some statistically significant results in some subgroup (
P
< 0.05). To some extent, probiotic supplements can increase the number of beneficial bacteria (especially
Bifidobacteria
) in the intestinal tract of patients with IBD.
Conclusions
Our results support the treatment of IBD (especially UC) with pro/pre/synbiotics, and synbiotics are more effective. Probiotic supplements that are based on
Lactobacillus
and
Bifidobacterium
or more than one strain are more likely to be beneficial for IBD remission. The dose of 10
10
–10
12
CFU/day may be a reference range for using probiotics to relieve IBD.
Abstract
Eicosapentaenoic acid (EPA), an omega-3 fatty acid, has been widely used to prevent cardiovascular disease (CVD) and treat brain diseases alone or in combination with docosahexaenoic acid ...(DHA). However, the impact of EPA and DHA supplementation on normal cognitive function and the molecular targets of EPA and DHA are still unknown. We show that acute administration of EPA impairs learning and memory and hippocampal LTP in adult and prepubescent mice. Similar deficits are duplicated by endogenously elevating EPA in the hippocampus in the transgenic fat-1 mouse. Furthermore, the damaging effects of EPA are mediated through enhancing GABAergic transmission via the 5-HT
6
R. Interestingly, DHA can prevent EPA-induced impairments at a ratio of EPA to DHA similar to that in marine fish oil via the 5-HT
2C
R. We conclude that EPA exhibits an unexpected detrimental impact on cognitive functions, suggesting that caution must be exercised in omega-3 fatty acid supplementation and the combination of EPA and DHA at a natural ratio is critical for learning and memory and synaptic plasticity.
Organic electrochemical transistors showing maximum transconductance (gm) at zero gate bias (VG) is desired but has long been a challenge. To date, few solutions to this issue are available. ...Light‐matter interplay is shown as rich sources for optogenetics, photodynamic therapy, and advanced electronics, but its potential in gm modulation are largely untapped. Herein, the challenge is addressed by unique light‐matter interplay in the newly emerged technique of organic photoelectrochemical transistor (OPECT), which is exemplified by dual‐ligand photosensitive metal–organic frameworks (DL‐PS‐MOFs)/TiO2 nanorods (NRs) gated poly(ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) OPECT under 425 nm light irradiation. Interestingly, the light stimulation on the DL‐PS‐MOFs can de‐dope PEDOT:PSS with altered transistor physics, achieving device showing maximum gm at zero VG and the simultaneous superior output of channel current. In connection to a cascade catalytic hairpin assembly‐rolling circle amplification strategy, such a device is then biologically interfaced with a miRNA‐triggered growth of DNA spheres for the sensitive detection of miRNA‐21 down to 0.12 fm. This work features a proof‐of‐concept study using light‐matter interplay to enable organic transistors showing maximum gm at zero VG and its sensitive biological interfacing application.
Herein, light‐matter interplay tune PEDOT:PSS OPECT showing maximum transconductance at zero gate bias and its biological interfacing application is realized for the first time, which is exemplified by dual ligand photosensitive metal–organic frameworks/TiO2 nanorods gated OPECT under 425 nm light irradiation. The proposed device exhibits good analytical performance for miRNA‐21 with a detection limit of 0.12 fm.
During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in ...other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences.
Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined.
At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7
44.9 years), had more cases with comorbidity (32.9%
19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7
4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0%
11.1%, death rate 7.3%
0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4
4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)).
There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.
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