Volatile compounds can be produced by fermentation from genetically engineered microorganisms. Escherichia coli strains are mainly used for isoprene production owing to their higher titers; however, ...this has thus far been confined to only strains BL21, BL21 (DE3), Rosetta, and BW25113. Here, we tested four groups of E. coli strains for improved isoprene production, including K‐12 (DH5α, BW25113, W3110, MG1655, XL1‐Blue, and JM109), B Rosetta (DE3), BL21, and BL21 (DE3), Crooks C, and Waksman W strains. The isoprene productivity of BL21 and MG1655 was remarkably higher than that of the others in 5‐L fermentation, and scale‐up fermentation (300 L) of BL21 was successfully performed. This system shows potential for biobased production of fuel and volatile compounds in industrial applications.
In this study, we compared 11 engineered recombinant Escherichia coli strains for improved isoprene production using one‐ and two‐vector systems. Our results showed that the isoprene productivity of strains BL21 and MG1655 was markedly higher than that of the other strains in 5‐L fermentation. Moreover, we achieved successful scale‐up fermentation using the BL21 strain in a 300‐L fermentor.
Many volatile compounds, such as isoprene, a precursor used in the synthesis of natural rubber, have been produced through fermentation using genetically engineered microorganisms. Despite this ...biotechnological success, measuring the concentrations of volatile compounds during fermentation is difficult because of their high volatility. In current systems, off-line analytical methods usually lead to product loss, whereas on-line methods raise the production cost due to the requirement of complex devices. Here, we developed a novel on-line gas chromatography (GC)-based system for analyzing the concentration of isoprene with the aim to minimize the cost and requirement for devices as compared to current strategies. In this system, a programmable logic controller is used to combine conventional GC with a syringe pump module (SPM) directly connected to the exhaust pipe of the fermentor, and isoprene-containing samples are continuously pumped from the SPM into the GC using an air cylinder recycle stream. We showed that this novel system enables isoprene analysis during fermentation with convenient equipment and without the requirement of an expensive desorption tube. Furthermore, this system may be extended to the detection of other volatile organic compounds in fermentation or chemical processes.
Display omitted
•This system analyzes the concentration of isoprene in aerobic fermentation.•PLC is used to combine conventional GC with SPM directly connected to fermenter.•Produced isoprene is continuously analyzed using the GC.•This system may be extended to the detection of other volatile organic compounds.
Background: Stretching and length test of hamstring muscles have been performed commonly to manage lower back pain (LBP) in sports rehabilitation. Previous literatures addressed that stretching ...techniques and length test of hamstring muscles should be performed with the pelvic maintained in an anterior tilt position. However, there is no study to determine the effectiveness of pressure biofeedback unit (PBU) to maintain in anterior pelvic tilting (APT) on length test and stretching of hamstring muscles.
Objective: To determine the effectiveness of hamstring muscles stretching using a PBU.
Methods: Forty participants with shortness of hamstrings randomized into two groups. Participants performed the active knee extension (AKE) stretching without (control group) or with PBU (intervention group) for four weeks. AKE tests without and with PBU were administered three times before and after hamstrings stretching by each group.
Results: The AKE test without PBU showed a significant main effect of time (
p
<
0
.
0
1
) but not of group (
p
=
0
.
5
5
) on the AKE angle. The AKE test with PBU showed a significant increase in the AKE angle in the post-intervention compared to the pre-intervention assessments in both groups (
p
<
0
.
0
1
). The difference of AKE angle between the pre- and post-intervention results was significantly greater in the intervention group than in the control group (
p
<
0
.
0
1
).
Conclusion: We recommend the use of a PBU to maintain the pelvic anterior tilting position when performing the AKE test or AKE stretching.
In the bioproduction of glutaric acid, an emerging bioplastic monomer, α-ketoglutaric acid (α-KG) is required as an amine acceptor for 4-aminobutyrate aminotransferase (GabT)-driven conversion of ...5-aminovalerate (5-AVA) to glutarate semialdehyde. Herein, instead of using expensive α-KG, an indirect α-KG supply system was developed using a relatively cheap alternative, monosodium glutamate (MSG), for l-glutamate oxidase (Gox)-based whole-cell conversion. Using 200 mM 5-AVA and 30 mM MSG initially with Gox, 67.1 mM of glutaric acid was produced. By applying the stepwise feeding strategy of MSG, the glutaric acid production capability was increased to 159.1 mM glutaric acid with a conversion yield of 79.6%. In addition, a buffer-free one-pot reaction from l-lysine was also applied in a 5 L bioreactor to evaluate its industrial applicability, resulting in a conversion yield of 54.2%. The system developed herein might have great potential for the large-scale, economically feasible production of glutaric acid by whole-cell conversion.
●Glutaric acid was successfully produced from L-lysine with 61.7% conversion yield by indirect supply of α-KG from MSG.●Indirect α-KG supplying system expressing Gox by stepwise feeding of MSG can replace expensive α-KG to relatively MSG.●The system can endow economic feasibility to whole cell bioconversion process by overcome the cost huddle of α-KG usage.
l-Threonine production was investigated in a minimal salt medium using
l-threonine-overproducing
Escherichia coli MT201, derived from
E. coli K-12. It was observed that dry cell weight reached 12.5 ...g/
l with 15.9 g/
l
l-threonine. To increase dry cell weight and
l-threonine production, the fermentation process was optimized. When biotin was added as growth factor,
l-threonine production reached 52.0 g/
l from 15.9 g/
l without biotin. Dry cell weight and
l-threonine production were further increased by continuous feeding of the feed media with an optimized
l-methionine concentration (5.0 g/
l). However, high-cell-density culture caused oxygen-limited condition, which resulted in the accumulation of organic acids. To overcome this problem, oxygen-enriched air was supplied to the fermentor with the minimal salt medium. Under these optimal conditions, we achieved an
l-threonine production of 80.2 g/
l in the minimal salt medium.
In this review paper, we introduce a self-phase controlled stimulated Brillouin scattering phase conjugate mirror (SC-SBS-PCM) and the Kumgang laser. The SC-SBS-PCM was proposed and demonstrated its ...success at the academic low power level, ${\sim}100~\text{mJ}@10~\text{Hz}$. The Kumgang laser is under development to verify whether the SC-SBS-PCM is operable at the kW level. It is a 4 kW beam combination laser combining four 1 kW beams using the SC-SBS-PCM. If the Kumgang laser functions successfully, it will be the most important step towards a Dream laser, a hypothetical laser with unlimited power and a high repetition rate.
Background
With improved short-term surgical outcomes, laparoscopic distal gastrectomy has rapidly gained popularity. However, the safety and feasibility of laparoscopic total gastrectomy (LTG) has ...not yet been proven due to the difficulty of the technique. This single-arm prospective multi-center study was conducted to evaluate the use of LTG for clinical stage I gastric cancer.
Methods
Between October 2012 and January 2014, 170 patients with pathologically proven, clinical stage I gastric adenocarcinoma located at the proximal stomach were enrolled. Twenty-two experienced surgeons from 19 institutions participated in this clinical trial. The primary end point was the incidence of postoperative morbidity and mortality at postoperative 30 days. The severity of postoperative complications was categorized according to Clavien–Dindo classification, and the incidence of postoperative morbidity and mortality was compared with that in a historical control.
Results
Of the enrolled patients, 160 met criteria for inclusion in the full analysis set. Postoperative morbidity and mortality rates reached 20.6% (33/160) and 0.6% (1/160), respectively. Fifteen patients (9.4%) had grade III or higher complications, and three reoperations (1.9%) were performed. The incidence of morbidity after LTG in this trial did not significantly differ from that reported in a previous study for open total gastrectomy (18%).
Conclusions
LTG performed by experienced surgeons showed acceptable postoperative morbidity and mortality for patients with clinical stage I gastric cancer.
•IRB/AML fixed-dose regimens show superior antihypertensive efficacy over IRB monotherapy.•A potential benefit of IRB/AML regimens was noted in the elderly and T2DM patients.•IRB/AML combinations are ...well-tolerated and have comparable safety to IRB monotherapy.
This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy.
Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP MSSBP ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography.
In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were −14.78 (12.35) mmHg, −21.47 (12.78) mmHg, and −8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were −13.30 (12.47) mmHg and −7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study.
The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability.
ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).
Endocrine treatment is recommended by clinical guidelines as the preferred treatment option for premenopausal as well as postmenopausal women with hormone receptor-positive, HER2-negative metastatic ...breast cancer. In real-world clinical practice, however, a substantial number of patients are treated with chemotherapy. We aimed to compare the clinical antitumour activity and safety of palbociclib plus endocrine therapy with that of capecitabine chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.
This multicentre, open-label, randomised, phase 2 study was done in 14 academic institutions in South Korea. Premenopausal women aged 19 years or older with hormone receptor-positive, HER2-negative breast cancer that had relapsed or progressed during previous tamoxifen therapy and with an Eastern Cooperative Oncology Group performance status of 0–2 were included. One line of previous chemotherapy for metastatic breast cancer was allowed. Patients were randomly assigned, using a random permuted block design (with a block size of two), to receive palbociclib plus combination endocrine therapy (oral exemestane 25 mg per day for 28 days and oral palbociclib 125 mg per day for 21 days every 4 weeks plus leuprolide 3·75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks). Randomisation was stratified by previous chemotherapy for metastatic breast cancer and visceral metastasis. The primary endpoint was progression-free survival. All analyses were done in a modified intention-to-treat population that excluded patients who did not receive study medication. This study is registered with ClinicalTrials.gov, NCT02592746, and is ongoing for follow-up of overall survival.
Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled, of whom 184 were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92). Six patients in the capecitabine group withdrew from the study before drug administration; therefore, 92 patients in the palbociclib plus endocrine therapy group and 86 patients in the capecitabine group were included in the modified intention-to-treat analyses. 46 (50%) of 92 patients in the palbociclib plus endocrine therapy group and 45 (51%) of 92 in the capecitabine group were treatment naive for metastatic breast cancer. During a median follow-up of 17 months (IQR 9–22), median progression-free survival was 20·1 months (95% CI 14·2–21·8) in the palbociclib plus endocrine therapy group versus 14·4 months (12·1–17·0) in the capecitabine group (hazard ratio 0·659 95% CI 0·437–0·994, one-sided log-rank p=0·0235). Treatment-related grade 3 or worse neutropenia was more common in the palbociclib plus endocrine therapy group than in the capecitabine group (69 75% of 92 vs 14 16% of 86 patients). 2 (2%) patients in the palbociclib plus endocrine therapy group and 15 (17%) patients in the capecitabine group had treatment-related serious adverse events. No treatment-related deaths occurred.
Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen.
Pfizer, Shinpoong, and Daewoong Korea and Takeda.
PDF
