Adults above 65 years of intention to use homecare hospice and a study on the factors influencing the perception of hospice·palliative care service.

BACKGROUND: This study is a descriptive correlation survey conducted to understand the effect of attitudes toward death, hospice palliative care perception, and knowledge on homecare hospice use intention for adult men and women aged 65 or older ones. AIM: This study identified factors affecting the intention to use homecare hospice and the perception of hospice·palliative care for adults aged 65 or older. METHODS: Researchers used tools which were intention to use homecare hospice, the hospice palliative care knowledge, death orientation, hospice palliative perception. RESULTS: The higher the perception of hospice·palliative care, for men than women, then they are the higher the willingness to use homecare hospice. In addition, the factors influencing the perception of hospice·palliative care of subjects who are willing to use homecare hospice were education and hospice·palliative care knowledge. CONCLUSION: By improving hospice·palliative care perception by acquiring hospice·palliative care knowledge, people will choose the place where they want to die. In addition, once there is an increasing demand for it, nations and Institutions can help to set up support homecare hospice. For this, campaigns, and education to provide knowledge and improve perception of hospice·palliative care must be continued at the socio-cultural level.

Physicochemical surrogates for in vitro toxicity assessment of liposomal amphotericin B.

Pharmaceutical toxicity evaluations often use in vitro systems involving primary cells, cell lines or red blood cells (RBCs). Cell-based analyses ('bioassays') can be cumbersome and typically rely on hard-to-standardize biological materials. Amphotericin B (AmB) toxicity evaluations are primarily based on potassium release from RBCs and share these limitations. This study evaluates the potential substitution of two physicochemical AmB toxicity approaches for the bioassay: Ultraviolet-visible spectroscopy (UV-vis) and in vitro drug release kinetics. UV-vis spectral analyses indicated that liposomal AmB's (L-AmB) main peak position (λmax) and peak ratio (OD346/OD322) are potential toxicity surrogates. Similarly, two first-order release parameters derived from USP-4 in vitro drug release analyses also provided linear relationships with toxicity. These were the initial, overall drug release rate and the ratio of loose to tight AmB pools. Positive slopes and high correlation coefficients (R2 > 0.9) characterized all interrelations between physicochemical parameters and toxicity. These tests converted the manufacturing variables' nonlinear (i.e., curvilinear) relationships with in vitro toxicity to linear responses. Three different toxicity attenuation approaches (2 manufacturing, 1 formulation), covering formulation composition and process aspects, support this approach's universality. These data suggest that one or more spectral and kinetic physicochemical tests can be surrogates for L-AmB in vitro toxicity testing.

Amphotericin B release rate is the link between drug status in the liposomal bilayer and toxicity.

Amphotericin B (AmB) is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections. Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer, which heat treatment (curing) modifies. Although toxicity was found related to aggregation status - loose aggregates significantly more toxic than tight aggregates - the precise mechanism linking aggregation and toxicity was not well understood. This study directly measured drug release rate from various AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state, drug release, and in vitro toxicity. UV-Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features: a ∼25 nm blue-shift of the main absorption peak (λmax) in aqueous buffer and a decrease in the OD346/OD322 ratio upon thermal curing, reflecting tighter aggregation. In vitro release testing (IVRT) data showed, by applying and fitting first-order release kinetic models for one or two pools, that curing impacts two significant changes: a 3-5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated, more thermodynamically stable drug pool. The kinetic data thus corroborated the trend independently deduced from the UV-Vis spectral data. The in vitro toxicity assay indicated a decreased toxicity with curing, as shown by the significantly increased concentration, causing half-maximal potassium release (TC50). The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation. This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release (directly measured rate constants), providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.

Multiphase Drug Distribution and Exchange in Oil-in-Water Nanoemulsion Revealed by High-Resolution 19F qNMR.

An oil-in-water (o/w) nanoemulsion (NE), composed of oil globules, stabilized by a surfactant, and dispersed in an aqueous phase, is increasingly developed in complex drug formulation. Kinetically stable NEs are used to formulate hydrophobic drugs and typically provide higher dosage strengths and better content uniformity. However, little is known accurately about drug distribution in its multiphase solution, especially for the possible drug presence in the surfactant (s) phase, the interface layer between the dispersed oil (o) and the continuous water (w) phases. Here, high-resolution 19F quantitative NMR spectroscopy was applied directly and noninvasively on an o/w NE drug product containing difluprednate (DFPN). The well-resolved 19F peaks of DFPN depended on the shielding molecules in each phase, which revealed mass-balanced DFPN distribution in multiple phases of (w), (s), and (o) of NE globules at a quantity of 1.8 ± 0.1, 35 ± 2, and 59 ± 3% per labeled content, respectively. Furthermore, the dilution-dependent 19F peak line broadening and shift suggested a millisecond dynamic exchange between the NE and the less-noticed smaller but thermodynamically stable microemulsion (ME) globules in NE solution. The high-resolution NMR result revealed that the drug availability could be quickly achieved using an o/w NE formulation because of the drug multiphase distribution and the ME-assisted fast drug exchange among globules.

Characterization of Complex Drug Formulations Using Cryogenic Scanning Electron Microscopy (Cryo-SEM).

The physicochemical properties of complex drug formulations, including liposomes, suspensions, and emulsions, are important for understanding drug release mechanisms, quality control, and regulatory assessment. It is ideal to characterize these complex drug formulations in their native hydrated state. This article describes the characterization of complex drug formulations in a frozen-hydrated state using cryogenic scanning electron microscopy (cryo-SEM). In comparison to other techniques, such as optical microscopy or room-temperature scanning electron microscopy, cryo-SEM combines the advantage of studying hydrated samples with high-resolution imaging capability. Detailed information regarding cryo-fixation, cryo-fracture, freeze-etching, sputter-coating, and cryo-SEM imaging is included in this article. A multivesicular liposomal complex drug formulation is used to illustrate the impact of different cryogenic sample preparation conditions. In addition to drug formulations, this approach can also be applied to biological samples (e.g., cells, bacteria) and soft-matter samples (e.g., hydrogels). © Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Basic Protocol 1: Cryo-fixation to preserve the native structure of samples using planchettes Alternate Protocol: Cryo-fixation to preserve the native structure of biological samples on sapphire disks Basic Protocol 2: Sample preparation for cross-sectional cryo-SEM imaging Basic Protocol 3: Cryo-SEM imaging and microanalysis.

Strongly Entangled Triplet Acyl-Alkyl Radical Pairs in Crystals of Photostable Diphenylmethyl Adamantyl Ketones.

Radical pairs generated in crystalline solids by bond cleavage reactions of triplet ketones offer the unique opportunity to explore a frontier of spin dynamics where rigid radicals are highly entangled as the result of short inter-radical distances, large singlet-triplet energy gaps (ΔEST), and limited spin-lattice relaxation mechanisms. Here we report the pulsed laser generation and detection of strongly entangled triplet acyl-alkyl radical pairs generated in nanocrystalline suspensions of 1,1-diphenylmethyl 2-ketones with various 3-admantyl substituents. The sought-after triplet acyl-alkyl radical pairs could be studied for the first time in the solid state by taking advantage of the efficient triplet excited state α-cleavage reactions of 1,1-diphenylmethyl ketones and the slow rate of CO loss from the acyl radicals, which would have to generate highly unstable phenyl and primary alkyl radicals or relatively unstable secondary and tertiary alkyl radicals. With the loss of CO prevented, the lifetime of the triplet acyl-alkyl radical pair intermediates is determined by intersystem crossing to the singlet radical pair state, which is followed by immediate bond formation to the ground state starting ketone. Experimental results revealed biexponential kinetics with long-lived components that account for ca. 87-92% of the transient population and lifetimes that extend to the range of 53-63 µs, the longest reported so far for this type of radical pair. Structural information inferred from the starting ketone will make it possible to analyze the affects of proximity and orientation of the singly occupied orbitals and potentially help set a path for the use of triplet radical pairs as qubits in quantum information technologies.

mTORC1 promotes cell growth via m6A-dependent mRNA degradation.

Dysregulated mTORC1 signaling alters a wide range of cellular processes, contributing to metabolic disorders and cancer. Defining the molecular details of downstream effectors is thus critical for uncovering selective therapeutic targets. We report that mTORC1 and its downstream kinase S6K enhance eIF4A/4B-mediated translation of Wilms' tumor 1-associated protein (WTAP), an adaptor for the N6-methyladenosine (m6A) RNA methyltransferase complex. This regulation is mediated by 5' UTR of WTAP mRNA that is targeted by eIF4A/4B. Single-nucleotide-resolution m6A mapping revealed that MAX dimerization protein 2 (MXD2) mRNA contains m6A, and increased m6A modification enhances its degradation. WTAP induces cMyc-MAX association by suppressing MXD2 expression, which promotes cMyc transcriptional activity and proliferation of mTORC1-activated cancer cells. These results elucidate a mechanism whereby mTORC1 stimulates oncogenic signaling via m6A RNA modification and illuminates the WTAP-MXD2-cMyc axis as a potential therapeutic target for mTORC1-driven cancers.

Computational studies of anaplastic lymphoma kinase mutations reveal common mechanisms of oncogenic activation.

Kinases play important roles in diverse cellular processes, including signaling, differentiation, proliferation, and metabolism. They are frequently mutated in cancer and are the targets of a large number of specific inhibitors. Surveys of cancer genome atlases reveal that kinase domains, which consist of 300 amino acids, can harbor numerous (150 to 200) single-point mutations across different patients in the same disease. This preponderance of mutations-some activating, some silent-in a known target protein make clinical decisions for enrolling patients in drug trials challenging since the relevance of the target and its drug sensitivity often depend on the mutational status in a given patient. We show through computational studies using molecular dynamics (MD) as well as enhanced sampling simulations that the experimentally determined activation status of a mutated kinase can be predicted effectively by identifying a hydrogen bonding fingerprint in the activation loop and the αC-helix regions, despite the fact that mutations in cancer patients occur throughout the kinase domain. In our study, we find that the predictive power of MD is superior to a purely data-driven machine learning model involving biochemical features that we implemented, even though MD utilized far fewer features (in fact, just one) in an unsupervised setting. Moreover, the MD results provide key insights into convergent mechanisms of activation, primarily involving differential stabilization of a hydrogen bond network that engages residues of the activation loop and αC-helix in the active-like conformation (in >70% of the mutations studied, regardless of the location of the mutation).

A study on depression among adolescents with asthma in South Korea using the 15th Korea Youth Risk Behaviour Web-Based Survey.

PURPOSE: This study investigated the factors that influence depression in adolescents diagnosed with asthma in South Korea, providing basic data supporting efforts to improve adolescents' mental health. METHODS: Multiple regression analysis was conducted on 4,020 subjects who had been diagnosed with lifelong asthma among the 57,303 respondents to the 15th Korea Youth Risk Behaviour Web-Based Survey from 2019. RESULTS: The participants were more likely to have depression if they were female, in middle school, their academic achievement was poor, they were drinkers or smokers, if they felt a very high amount of stress, and if they experienced very inadequate recovery from fatigue. Adolescents with asthma were 9.00 times more likely to experience depression when they felt a very high amount of stress (95% confidence interval [CI]=5.51-14.69, p<.001) than when they felt no stress. CONCLUSION: Given these factors, measures to improve the mental health of adolescents should be developed and expanded, especially to decrease their stress levels. A separate program that is different from the school's regular health curriculum should be developed to manage the stress levels of adolescents with asthma, such as an after-school program or a program conducted at a local community centre.

Comparison of conventional and fibreoptic-guided advance of left-sided double-lumen tube during endobronchial intubation: A randomised controlled trial.

BACKGROUND: Postoperative sore throat and airway injuries are relatively common after double-lumen tube (DLT) intubation. OBJECTIVE: The current study aimed to evaluate the effects of fibreoptic-guided advance of DLT on postoperative sore throat and airway injuries associated with intubation. DESIGN: A randomised controlled study. SETTING: Tertiary hospital, Seongnam, Korea, from January 2018 to January 2019. PATIENTS: One hundred twenty three patients undergoing one-lung ventilation with a left-side DLT were randomised into two groups: 62 in the conventional group and 61 in the fibreoptic-guided group. INTERVENTION: After entering the glottis, the DLT was rotated left 90° and advanced blindly into the left main bronchus in the conventional group. In the fibreoptic-guided group, DLT was advanced into the main bronchus under the guide of fibreoptic bronchoscope, which had been passed through the bronchial lumen and inserted into the left main bronchus. MAIN OUTCOME MEASURES: The primary outcome was postoperative sore throat at 24 h after operation. The airway injuries were also examined using a bronchoscope during extubation. RESULTS: At postoperative 24 h, the fibreoptic-guided group showed lower pain score (P = 0.001) and lower incidence (risk ratio [95% CI]: 0.2 [0.1 to 0.5], P < 0.001) of sore throat, compared with the conventional group. Moreover, tracheal injury was more severe in the conventional group than in the fibreoptic group (P = 0.003). Vocal cord injuries also occurred less frequently in the fibreoptic-guided group (risk ratio [95% CI]: 0.4 [0.2 to 1.0], P = 0.036). CONCLUSION: The fibreoptic-guided advancement seems to reduce irritation to the airway, leading less postoperative complications. TRIAL REGISTRATION: ClinicalTrials.gov, registration number: NCT03368599.

Structural Insights into the Activation of mTORC1 on the Lysosomal Surface.

Using cryo-electron microscopy and molecular characterization, David Sabatini and colleagues provide crucial new insights that validate and expand their model of how amino acids are sensed and signal at the lysosome to activate mechanistic target of rapamycin complex 1 (mTORC1) and cell growth-regulating processes. This work also reveals new therapeutic opportunities for mTORC1-driven diseases.

A drug discovery platform to identify compounds that inhibit EGFR triple mutants.

Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease. Historically, therapeutics targeting RTKs have been identified using in vitro kinase assays. Due to frequent development of drug resistance, however, there is a need to identify more diverse compounds that inhibit mutated but not wild-type RTKs. Here, we describe MaMTH-DS (mammalian membrane two-hybrid drug screening), a live-cell platform for high-throughput identification of small molecules targeting functional protein-protein interactions of RTKs. We applied MaMTH-DS to an oncogenic epidermal growth factor receptor (EGFR) mutant resistant to the latest generation of clinically approved tyrosine kinase inhibitors (TKIs). We identified four mutant-specific compounds, including two that would not have been detected by conventional in vitro kinase assays. One of these targets mutant EGFR via a new mechanism of action, distinct from classical TKI inhibition. Our results demonstrate how MaMTH-DS is a powerful complement to traditional drug screening approaches.

The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma.

PURPOSE: EGFR exon 19 deletion (Ex19Del) mutations account for approximately 60% of lung cancer-associated EGFR mutations and include a heterogeneous group of mutations. Although they are associated with benefit from tyrosine kinase inhibitors (TKI), the relative inhibitor sensitivity of individual Ex19Del mutations is unknown.Experimental Design: We studied the TKI sensitivity and structural features of common Ex19Del mutations and the consequences for patient outcomes on TKI treatment. RESULTS: We found that the L747-A750>P mutation, which represents about 4% of all Ex19Del mutations, displays unique inhibitor selectivity. L747-A750>P differs from other Ex19Del mutations in not being suppressed completely by erlotinib or osimertinib, yet is completely inhibited by low doses of afatinib. The HCC4006 cell line (with the L747-A750>P mutation) exhibited increased sensitivity to afatinib over erlotinib and osimertinib, and computational modeling suggests explanations for this sensitivity pattern. Clinically, patients with EGFR L747-A750>P mutant tumors showed inferior outcomes when treated with erlotinib than patients with E746-A750 mutant tumors. CONCLUSIONS: These results highlight important differences between specific Ex19Del mutations that may be relevant for optimizing TKI choice for patients.

Computational algorithms for in silico profiling of activating mutations in cancer.

Methods to catalog and computationally assess the mutational landscape of proteins in human cancers are desirable. One approach is to adapt evolutionary or data-driven methods developed for predicting whether a single-nucleotide polymorphism (SNP) is deleterious to protein structure and function. In cases where understanding the mechanism of protein activation and regulation is desired, an alternative approach is to employ structure-based computational approaches to predict the effects of point mutations. Through a case study of mutations in kinase domains of three proteins, namely, the anaplastic lymphoma kinase (ALK) in pediatric neuroblastoma patients, serine/threonine-protein kinase B-Raf (BRAF) in melanoma patients, and erythroblastic oncogene B 2 (ErbB2 or HER2) in breast cancer patients, we compare the two approaches above. We find that the structure-based method is most appropriate for developing a binary classification of several different mutations, especially infrequently occurring ones, concerning the activation status of the given target protein. This approach is especially useful if the effects of mutations on the interactions of inhibitors with the target proteins are being sought. However, many patients will present with mutations spread across different target proteins, making structure-based models computationally demanding to implement and execute. In this situation, data-driven methods-including those based on machine learning techniques and evolutionary methods-are most appropriate for recognizing and illuminate mutational patterns. We show, however, that, in the present status of the field, the two methods have very different accuracies and confidence values, and hence, the optimal choice of their deployment is context-dependent.

Transient Kinetics and Quantum Yield Studies of Nanocrystalline α-Phenyl-Substituted Ketones: Sorting Out Reactions from Singlet and Triplet Excited States.

Recent work has shown that diarylmethyl radicals generated by pulsed laser excitation in nanocrystalline (NC) suspensions of tetraarylacetones constitute a valuable probe for the detailed mechanistic analysis of the solid-state photodecarbonylation reaction. Using a combination of reaction quantum yields and laser flash photolysis in nanocrystalline suspensions of ketones with different substituents on one of the α-carbons, we are able to suggest with confidence that a significant fraction of the initial α-cleavage reaction takes place from the ketone singlet excited state, that the originally formed diarylmethyl-acyl radical pair loses CO in the crystal with time constants in the sub-nanosecond regime, and that the secondary bis(diarylmethyl) triplet radical pair has a lifetime limited by the rate of intersystem crossing of ca. 70 ns.

Triplet Sensitized Photodenitrogenation of Δ2-1,2,3-Triazolines To Form Aziridines in Solution and in the Crystalline State: Observation of the Triplet 1,3-Alkyl-aminyl Biradical.

Taking advantage of an operationally simple technique to perform transmission pump-probe spectroscopy in crystalline solids, based on the use nanocrystalline suspensions in water, we analyzed the intermediates in the photodenitrogenation of a Δ2-1,2,3-triazoline bearing a benzophenone group that served as an internal triplet sensitizer. Measurements carried out in acetonitrile solution revealed the formation of a transient with a λmax= 570 nm with a lifetime of 70 ns. Measurements in the solid state displayed an analogous blue-shifted transient with a λmax= 510 nm that first grows and then decays with time constants of 63 and 270 ns, respectively. Based on the comparison of the observed transient spectra with the one obtained from an independently generated aminyl radical, we assign it to the corresponding 1,3,-alkyl-aminyl biradical. We conclude that triplet state denitrogenation and the subsequent intersystem crossing-limited product formation are slower in the solid state than in solution.

Generation and Reactivity Studies of Diarylmethyl Radical Pairs in Crystalline Tetraarylacetones via Laser Flash Photolysis Using Nanocrystalline Suspensions.

The nanosecond electronic spectra and kinetics of the radical pairs from various crystalline tetraarylacetones were obtained using transmission laser flash photolysis methods by taking advantage of aqueous nanocrystalline suspensions in the presence of submicellar CTAB, which acts as a surface passivator. After showing that all tetraarylacetones react efficiently by a photodecarbonylation reaction in the crystalline state, we were able to detect the intermediate radical pairs within the ca. 8 ns laser pulse of our laser setup. We showed that the solid-state spectra of the radical pairs are very similar to those detected in solution, with λmax in the 330-360 nm range. Kinetics in the solid state was observed to be biexponential and impervious to the presence of oxygen or variations in laser power. A relatively short-lived component (0.3-1.7 µs) accounts for only 3-8% of the total decay with a longer-lived component having a time constant in the range of 40-90 µs depending on the nature of the substituents.

Airway Management Protocol After Anterior Cervical Spine Surgery: Analysis of the Results of Risk Factors Associated With Airway Complication.

STUDY DESIGN: Retrospective comparative cohort analysis. OBJECTIVE: To evaluate the effect of postoperative airway management protocol (ASAN Extubation Protocol, AEP) on incidence of airway complications for patients undergoing anterior cervical spine surgery (ACSS). BACKGROUND: Postoperative airway compromise remains crucial for patients undergoing ACSS. Despite the potential severity of these complications, the data in the published literature addressing this issue is sparse. METHODS: A retrospective cohort study was performed regarding airway complications (postoperative airway edema requiring unplanned reintubation or tracheostomy) between groups of patients undergoing ACSS before and after applying our standardized protocol (AEP) for postoperative extubation. The AEP was developed based on 5 clinical risk factors reported having relation to airway complication. Postoperative patients with any oneor more risk factors were kept intubated for at least overnight and extubation was conducted according to the amount of prevertebral soft tissue swelling. RESULTS: A total of 538 ACSS patients were identified from 2008 to 2016. The nonprotocol group (before protocol application, 275 patients) and the Protocol group (after protocol, 263 patients) were compared; airway complication rates were significantly different between two groups (nonprotocol: 3.64% (10/275) vs. PROTOCOL: 0.76% (2/263), P = 0.024). The possible factors that may increase airway complication include operative indications (P = 0.002), trauma (P = 0.000), medical comorbidity risk (P = 0.011), combined anterior and posterior surgery (P = 0.002), and operation time longer than 5 hours (P = 0.045). In multivariate analysis, medical comorbidity risk, trauma, and airway protocol adoption were significant factors. AEP reduced the airway complication rate by odds ratio 0.125 (P = 0.013). CONCLUSION: Postoperative airway complication is not very common after ACSS. AEP contributed to reduce the incidence of airway complications. The potentially life-threatening event of loss of airway patency, even though it is a rare complication, should be cautiously analyzed with identification of risk factors before the surgery. LEVEL OF EVIDENCE: 2.

Photochemistry and Transmission Pump-Probe Spectroscopy of 2-Azidobiphenyls in Aqueous Nanocrystalline Suspensions: Simplified Kinetics in Crystalline Solids.

Aqueous nanocrystalline suspensions provide a simple and efficient medium for performing transmission spectroscopy measurements in the solid state. In this Letter we describe the use of laser flash photolysis methods to analyze the photochemistry of 2-azidobiphenyl and several aryl-substituted derivatives. We show that all the crystalline compounds analyzed in this study transform quantitatively into carbazole products via a crystal-to-crystal reconstructive phase transition. While the initial steps of the reaction cannot be followed within the time resolution of our instrument (ca. 8 ns), we detected the primary isocarbazole photoproducts and analyzed the kinetics of their formal 1,5-H shift reactions, which take place in time scales that range from a few nanoseconds to several microseconds. It is worth noting that the high reaction selectivity observed in the crystalline state translates into a clean and simple kinetic process compared to that in solution.

Application of an oxygen-inducible nar promoter system in metabolic engineering for production of biochemicals in Escherichia coli.

The nar promoter, a dissolved oxygen (DO)-dependent promoter in Escherichia coli, is simply induced and functional in any cell growth phase, which are advantageous for producing biochemicals/fuels on an industrial scale. To demonstrate the feasibility of using the nar promoter in the metabolic engineering of biochemicals/biofuels in E. coli, three target pathways were examined: the d-lactate, 2,3-butandiol (2,3-BDO), and 1,3-propanediol (1,3-PDO) pathways consisting of one, three, and six genes, respectively. Each pathway gene was expressed under the control of the nar promoter. When the ldhD gene was expressed in fed-batch culture, the titer, yield, and productivity of d-lactate were 113.12 ± 2.37 g/L, 0.91 ± 0.07 g/g-glucose, and 4.19 ± 0.09 g/L/h, respectively. When three 2,3-BDO pathway genes (ilvBN, aldB, bdh1) were expressed in fed-batch culture, the titer, yield, and productivity of (R,R)-2,3-BDO were 48.0 ± 8.48 g/L, 0.43 ± 0.07 g/g glucose, and 0.76 ± 0.13 g/L/h, respectively. When six 1,3-PDO pathway genes (dhaB1B2B3, yqhD, gdrA, and gdrB) were expressed in fed-batch culture, the titer, yield, and productivity of 1,3-PDO were 15.8 ± 0.62 g/L, 0.35 ± 0.01 g/g-glycerol, and 0.25 ± 0.01 g/L/h, respectively. Based on the reasonable performance comparable to that observed in previous studies using different promoters in metabolic engineering, the nar promoter can serve as a controlled expression tool for developing a microbial system to efficiently produce biochemicals and biofuels. Biotechnol. Bioeng. 2017;114: 468-473. © 2016 Wiley Periodicals, Inc.