High-resolution 3-D scanning electron microscopy (SEM) images of DOTTM polynucleotides (PN): Unique scaffold characteristics and potential applications in biomedicine.

INTRODUCTION: Polynucleotides (PN) are becoming more prominent in aesthetic medicine. However, the structural characteristics of PN have not been published and PN from different companies may have different structural characteristics. This study aimed to elucidate the structural attributes of DOT™ PN and distinguish differences with polydeoxyribonucleotides (PDRN) using high-resolution scanning electron microscopy (SEM) imaging. MATERIALS AND METHODS: DOT™ PN was examined using a Quanta 3-D field emission gun (FEG) Scanning Electron Microscope (SEM). Sample preparation involved cryogenic cooling, cleavage, etching, and metal coating to facilitate high-resolution imaging. Cryo-FIB/SEM techniques were employed for in-depth structural analysis. RESULTS: PDRN exhibited an amorphous structure without distinct features. In contrast, DOT™ PN displayed well-defined polyhedral shapes with smooth, uniformly thick walls. These cells were empty, with diameters ranging from 3 to 8 micrometers, forming a seamless tessellation pattern. DISCUSSION: DOT™ PN's distinct geometric tessellation design conforms to the principles of biotensegrity, providing both structural reinforcement and integrity. The presence of delicate partitions and vacant compartments hints at possible uses in the field of pharmaceutical delivery systems. Within the realms of beauty enhancement and regenerative medicine, DOT™ PN's capacity to bolster cell growth and tissue mending could potentially transform approaches to rejuvenation treatments. Its adaptability becomes apparent when considering its contributions to drug administration and surgical procedures. CONCLUSION: This study unveils the intricate structural scaffold features of DOT™ PN for the first time, setting it apart from PDRN and inspiring innovation in biomedicine and materials science. DOT™ PN's unique attributes open doors to potential applications across healthcare and beyond.

Porphyrin-based supramolecular polymers.

Porphyrin derivatives are ubiquitous in bio-organisms and are associated with proteins that play important biological roles, such as oxygen transport, photosynthesis, and catalysis. Porphyrins are very fascinating research objects for chemists, physicists, and biologists owing to their versatile chemical and physical properties. Porphyrin derivatives are actively used in various fields, such as molecular recognition, energy conversion, sensors, biomedicine, and catalysts. Porphyrin derivatives can be used as building blocks for supramolecular polymers because their primitive structures have C4 symmetry, which allows for the symmetrical introduction of self-assembling motifs. This review describes the fabrication of porphyrin-based supramolecular polymers and novel discoveries in supramolecular polymer growth. First, we summarise the (i) design concepts, (ii) growth mechanism and (iii) analytical methods of porphyrin-based supramolecular polymers. Then, the examples of porphyrin-based supramolecular polymers formed by (iv) hydrogen bonding, (v) metal coordination-based interaction, (vi) host-guest complex formation, and (vii) others are summarised. Finally, (viii) applications and perspectives are discussed. Although supramolecular polymers, in a broad sense, can include either two-dimensional (2D) networks or three-dimensional (3D) porous polymer structures; this review mainly focuses on one-dimensional (1D) fibrous supramolecular polymer structures.

Prognostic serum biomarkers in non-tuberculous mycobacterial pulmonary disease.

Increased serum C-reactive protein (CRP) levels at the time of diagnosis predicted worse prognosis in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD). Approximately one-quarter of the patients with NTM-PD had higher than normal CRP levels, and this elevation led to a higher risk of death.

Anatomical proposal of local anesthesia injection for median nerve block in treating hyperhidrosis with botulinum neurotoxin.

INTRODUCTION: Hyperhidrosis, causing excessive sweat, can be treated with Botulinum neurotoxin injection. Botulinum toxin, an effective and safe treatment for hyperhidrosis, unfortunately involves significant pain due to multiple injections. This study aims to propose a more efficient and less painful approach to nerve blocks for relief, by identifying optimal injection points to block the median nerve, thereby enhancing palmar hyperhidrosis treatment. METHODS: This study, involving 52 Korean cadaver arms (mean age 73.5 years), measured the location of the median nerve relative to the transverse line at the pisiform level to establish better nerve block injection sites. RESULTS: In between the extensor carpi radialis and palmaris longus, the median nerve was located at an average distance of 47.39 ± 6.43 mm and 29.39 ± 6.43 mm from the transverse line at the pisiform level. DISCUSSION: To minimize discomfort preceding the botulinum neurotoxin injection, we recommend the optimal injection site for local anesthesia to be located 4 cm distal to the transverse line of the pisiform, within the tendons of the palmaris longus and flexor carpi radialis muscles.

Botulinum neurotoxin injection in the deltoid muscle: application to cosmetic shoulder contouring.

BACKGROUND AND OBJECTIVES: This study describes the intramuscular nerve branching of the deltoid muscle in relation to shoulder surface anatomy, with the aim of providing essential information regarding the most appropriate sites for botulinum neurotoxin injection during shoulder line contouring. METHODS: The modified Sihler's method was used to stain the deltoid muscles (16 specimens). The intramuscular arborization areas of the specimens were demarcated using the marginal line of the muscle origin and the line connecting the anterior and posterior upper edges of the axillary region. RESULTS: The intramuscular neural distribution of the deltoid muscle had the greatest arborization patterns in the area between the horizontal 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line in middle deltoid bellies. The greatest part of the posterior circumflex artery and axillary nerve ran below the areas with the highest aborizations. CONCLUSION: We propose that botulinum neurotoxin injections should be administered in the area between the 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line on middle deltoid bellies. Accordingly, clinicians will ensure minimal dose injections and fewer adverse effects of the botulinum neurotoxin injection. Deltoid intramuscular injections, such as vaccines and trigger point injections, should ideally be adapted according to our results.

Expression Profiles of Immune Cells after Propofol or Sevoflurane Anesthesia for Colorectal Cancer Surgery: A Prospective Double-blind Randomized Trial.

BACKGROUND: The antitumor effects of natural killer cells, helper T cells, and cytotoxic T cells after cancer surgery were reported previously. This study hypothesized that propofol-based anesthesia would have fewer harmful effects on immune cells than volatile anesthetics-based anesthesia during colorectal cancer surgery. METHODS: In total, 153 patients undergoing colorectal cancer surgery were randomized and included in the analysis. The primary outcome was the fraction of circulating natural killer cells over time in the propofol and sevoflurane groups. The fractions of circulating natural killer, type 1, type 17 helper T cells, and cytotoxic T cells were investigated. The fractions of CD39 and CD73 expressions on circulating regulatory T cells were investigated, along with the proportions of circulating neutrophils, lymphocytes, and monocytes. RESULTS: The fraction of circulating natural killer cells was not significantly different between the propofol and sevoflurane groups until 24 h postoperatively (20.4 ± 13.4% vs. 20.8 ± 11.3%, 17.9 ± 12.7% vs. 20.7 ± 11.9%, and 18.6 ± 11.6% vs. 21.3 ± 10.8% before anesthesia and after 1 and 24 h after anesthesia, respectively; difference [95% CI], -0.3 [-4.3 to 3.6], -2.8 [-6.8 to 1.1], and -2.6 [-6.2 to 1.0]; P = 0.863, P = 0.136, and P = 0.151 before anesthesia and after 1 and 24 h, respectively). The fractions of circulating type 1 and type 17 helper T cells, cytotoxic T cells, and CD39+ and CD73+ circulating regulatory T cells were not significantly different between the two groups. The neutrophil to lymphocyte ratio in both groups remained within the normal range and was not different between the groups. CONCLUSIONS: Propofol-based anesthesia was not superior to sevoflurane-based anesthesia in terms of alleviating suppression of immune cells including natural killer cells and T lymphocytes during colorectal cancer surgery.

Mesoscale Frank-Kasper Crystal Structures from Dendron Assembly by Controlling Core Apex Interactions.

Single-component polymeric materials open up a great potential for self-assembly into mesoscale complex crystal structures that are known as Frank-Kasper (FK) phases. Predicting the packing structures of the soft-matter spheres, however, remains a challenge even when the molecular design is precisely known. Here, we investigate the role of the molecules' enthalpic interaction in determining the low-symmetry crystal structures. To this end, we synthesize architecturally asymmetric dendrons by varying their apex functionalities and examine the packing structures of the second-generation (G2) dendritic wedges. Our work shows that weakening the hydrogen bonding of the dendron apex makes the particles softer and smaller, and leads to the formation of various FK structures at lower temperatures, including the new observation of a FK C14 phase in the cone-shaped dendron systems. As a consequence of the free energy balance between the particle's interfacial tension and the chain's stretching, various packing structures are mainly tuned by designing the hydrogen bonding interaction.

Safety, feasibility, and efficacy of strengthening exercise in Duchenne muscular dystrophy.

BACKGROUND: This two-part study explored the safety, feasibility, and efficacy of a mild-moderate resistance isometric leg exercise program in ambulatory boys with Duchenne muscular dystrophy (DMD). METHODS: First, we used a dose escalation paradigm with varying intensity and frequency of leg isometric exercise to determine the dose response and safety in 10 boys. Second, we examined safety and feasibility of a 12-wk in-home, remotely supervised, mild-moderate intensity strengthening program in eight boys. Safety measures included T2 MRI, creatine kinase levels, and pain. Peak strength and function (time to ascend/descend four stairs) were also measured. RESULTS: Dose-escalation revealed no signs of muscle damage. Seven of the eight boys completed the 12-wk in-home program with a compliance of 84.9%, no signs of muscle damage, and improvements in strength (knee extensors P < .01; knee flexors P < .05) and function (descending steps P < .05). CONCLUSIONS: An in-home, mild-moderate intensity leg exercise program is safe with potential to positively impact both strength and function in ambulatory boys with DMD.

Enhancement of electrode performance through surface modification using carbon nanotubes and porous gold nanostructures.

Recently, the demand for the sensitive detection of nanomaterials and biomolecules has been increasing for evaluating the toxicity of nanomaterials and early diagnosis of diseases. Although many studies have developed new detection assays, these are heavily influenced by the capabilities of the detection equipment. Therefore, the aim of the present study was to improve electrode performance by modifying the surface of the detection electrode using a simple method. Electrode surface modification was performed using carbon nanotubes (CNT) and porous gold nanostructures (NS) with excellent electrical and chemical properties. Through the simple physical deposition of CNT and electrochemical reduction of NS, the increasement of the electrode surface area was achieved. Because of the CNTs attached to the electrodes at the first step, the metal ions constituting the NS can adhere well to the electrodes. Nanoparticles with a porous structure can be generated through electrochemical reduction (cyclic voltammetry) of metal ions attached to electrodes. Consequently, the surface area of the electrode increased and electrochemical performance was improved (confirmed by atomic force microscopy, Nyquist plot and Bode plot). To quantitatively confirm the improvement of electrode performance according to the surface change through the proposed treatment technique, DNA was detected. Unlike previous surface modification studies, the developed surface treatment technique can be applied to a variety of detection equipment. To confirm this, the detection was performed using two detection devices with different operating principles. DNA detection using the two types of equipment confirmed that the detection limit was increased by approximately 1000-fold through applying a simple surface treatment. In addition, this method is applicable to detect various sizes of nanomaterials. The method proposed in this study is simple and has the advantage that it can be applied to various devices and various materials.

Low Temperature and Cold Stress Significantly Increase Saxitoxins (STXs) and Expression of STX Biosynthesis Genes sxtA4 and sxtG in the Dinoflagellate Alexandrium catenella.

Toxic dinoflagellate Alexandrium spp. produce saxitoxins (STXs), whose biosynthesis pathway is affected by temperature. However, the link between the regulation of the relevant genes and STXs' accumulation and temperature is insufficiently understood. In the present study, we evaluated the effects of temperature on cellular STXs and the expression of two core STX biosynthesis genes (sxtA4 and sxtG) in the toxic dinoflagellate Alexandrium catenella Alex03 isolated from Korean waters. We analyzed the growth rate, toxin profiles, and gene responses in cells exposed to different temperatures, including long-term adaptation (12, 16, and 20 °C) and cold and heat stresses. Temperature significantly affected the growth of A. catenella, with optimal growth (0.49 division/day) at 16 °C and the largest cell size (30.5 µm) at 12 °C. High concentration of STXs eq were detected in cells cultured at 16 °C (86.3 fmol/cell) and exposed to cold stress at 20→12 °C (96.6 fmol/cell) compared to those at 20 °C and exposed to heat stress. Quantitative real-time PCR (qRT-PCR) revealed significant gene expression changes of sxtA4 in cells cultured at 16 °C (1.8-fold) and cold shock at 20→16 °C (9.9-fold). In addition, sxtG was significantly induced in cells exposed to cold shocks (20→16 °C; 19.5-fold) and heat stress (12→20 °C; 25.6-fold). Principal component analysis (PCA) revealed that low temperature (12 and 16 °C) and cold stress were positively related with STXs' production and gene expression levels. These results suggest that temperature may affect the toxicity and regulation of STX biosynthesis genes in dinoflagellates.

Effect of deep neuromuscular blockade on serum cytokines and postoperative delirium in elderly patients undergoing total hip replacement: A prospective single-blind randomised controlled trial.

BACKGROUND: Deep neuromuscular blockade (NMB) may reduce muscle injury and related inflammation. The inflammation is one of the pathophysiological processes of peri-operative complications. OBJECTIVE: To compare the degree of inflammation and related postoperative complications including postoperative delirium (POD) and peri-operative bleeding according to the degree of NMB during general anaesthesia for total hip replacement. DESIGN: A prospective, single-blind, randomised controlled trial. SETTING: Tertiary, university hospital, single centre. PATIENTS: Eighty-two patients undergoing total hip replacement surgery were included in the final analysis. INTERVENTIONS: Moderate (Mod) and deep (Deep) NMB groups. MAIN OUTCOME MEASURES: The changes in inflammatory cytokines were measured. The incidence of POD was evaluated by using confusion assessment method (CAM). The differences of postoperative bleeding and peri-operative oxygenation in both groups were also measured. RESULTS: The NMB reversal duration was significantly longer in the Mod NMB group than in the Deep NMB group. Changes in interleukin-6 were significantly smaller in the Deep NMB group than in the Mod NMB group (P < 0.001). The incidence of POD was not significantly different between groups (34 versus 17% in Mod and Deep NMB groups, respectively; P = 0.129). The amount of postoperative bleeding until postoperative day 2 was significantly greater in the Mod NMB group than in the Deep NMB group (P = 0.027). CONCLUSION: Our findings suggest that inflammation related to peri-operative complications could be associated with the depth of NMB during total hip replacement. However, the incidence of POD might not be associated to the depth of NMB. TRIAL REGISTRATION: National Library of Medicine (NLM) at the National Institutes of Health (NIH) of United States. (Identifier: NCT02507609). Online address: http://clinicaltrials.gov.

The Preventive Effect of the Phenotype of Tumour-Associated Macrophages, Regulated by CD39, on Colon Cancer in Mice.

BACKGROUND: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. METHODS: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. RESULTS: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. CONCLUSION: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.

Valgus stress ultrasound for medial ulnar collateral ligament injuries in athletes: is ultrasound alone enough for diagnosis?

BACKGROUND: We hypothesized that valgus stress ultrasound would be useful for both identifying medial ulnar collateral ligament (MUCL) tears and assessing the severity of the tears. Hence, we performed valgus stress ultrasound of the elbow in athletes with MUCL injuries, confirmed by magnetic resonance imaging (MRI), to determine whether ultrasound can be used as a diagnostic tool. METHODS: Stress ultrasound and MRI data from 146 athletes with medial elbow pain were compared prospectively. MRI findings for MUCL injuries were classified into 3 levels as follows: low-grade partial tear (≤50%), high-grade partial tear (>50%), and complete tear. The degree of joint laxity on stress ultrasound was evaluated by measuring joint gapping after applying a 2.5-kg load to the wrist. Joint gapping was measured at 30° and 90° of elbow flexion for the dominant arm and nondominant arm, and the differences between the dominant and nondominant arms were determined. RESULTS: A higher degree of MUCL injury on MRI was associated with greater joint gapping in the medial elbow on stress ultrasound. At 30° of elbow flexion, the cutoff value for complete MUCL rupture was 0.5 mm (P < .001), with a sensitivity and specificity of 88.1% and 61.5%, respectively. At 90° of elbow flexion, the cutoff value for complete MUCL rupture was 1.0 mm (P < .001), with a sensitivity and specificity of 81.0% and 66.4%, respectively. CONCLUSION: Stress ultrasound can be used to diagnose complete MUCL tears in athletes when joint gapping is greater than 0.5 mm at 30° of elbow flexion and greater than 1 mm at 90° of elbow flexion.

Does anchor insertion angle or placement of the suture anchor affect glenoid rim fracture occurrence after arthroscopic Bankart repair?

BACKGROUND: The purposes were to compare the characteristics of 2 groups of patients who underwent revision Bankart repair with and without glenoid rim fractures and to examine risk factors for glenoid rim fractures. METHODS: We retrospectively analyzed 39 patients who needed revision surgery after arthroscopic Bankart repair and identified 19 patients with and 20 patients without glenoid rim fractures. The insertion angle of the suture anchor, anchor position on the glenoid, and demographic data were compared between the groups. RESULTS: The mean anchor insertion angles in the glenoid fracture group (group F) at the 2-, 3-, 4-, and 5-o'clock positions were 64°, 58°, 55°, and 55°, respectively; those in the no-fracture group (group R) were 60°, 63°, 60°, and 55°, respectively (P = .630, P = .207, P = .166, and P = .976, respectively). At the 5-o'clock position, anchors were fixed to the glenoid face in 13 cases in group F and in 3 cases in group R (P = .040). Although age (P = .529) and sex (P = 1.0) did not differ between the groups, elite and professional athletes had a significantly higher incidence of glenoid rim fractures (P = .009). CONCLUSION: The anchor insertion angle did not affect glenoid rim fracture occurrence after arthroscopic Bankart repair. However, the placement of the suture anchor at the 5-o'clock position on the glenoid face could increase the risk of glenoid rim fracture after trauma. Athletes were more likely to have glenoid rim fractures owing to major trauma after arthroscopic Bankart repair.

Therapeutic Potential of Repeated Intravenous Transplantation of Human Adipose-Derived Stem Cells in Subchronic MPTP-Induced Parkinson's Disease Mouse Model.

Parkinson's disease (PD) is the second most common neurodegenerative disease, which is clinically and pathologically characterized by motor dysfunction and the loss of dopaminergic neurons in the substantia nigra, respectively. PD treatment with stem cells has long been studied by researchers; however, no adequate treatment strategy has been established. The results of studies so far have suggested that stem cell transplantation can be an effective treatment for PD. However, PD is a progressively deteriorating neurodegenerative disease that requires long-term treatment, and this has been insufficiently studied. Thus, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASC) for repeated vein transplantation over long-term in an animal model of PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice, hASCs were administered on the tail vein six times at two-week intervals. After the last injection of hASCs, motor function significantly improved. The number of dopaminergic neurons present in the nigrostriatal pathway was recovered using hASC transplantation. Moreover, the administration of hASC restored altered dopamine transporter expression and increased neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), in the striatum. Overall, this study suggests that repeated intravenous transplantation of hASC may exert therapeutic effects on PD by restoring BDNF and GDNF expressions, protecting dopaminergic neurons, and maintaining the nigrostriatal pathway.

Synthesis and evaluation of novel potent TSPO PET ligands with 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide.

Translocator protein (TSPO) expression is closely related with neuroinflammation and neuronal damage which might cause several central nervous system diseases. Herein, a series of TSPO ligands (11a-c and 13a-d) with a 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide structure were prepared and evaluated via an in vitro binding assay. Most of the novel ligands exhibited a nano-molar affinity for TSPO, which was better than that of DPA-714. Particularly, 11a exhibited a subnano-molar TSPO binding affinity with suitable lipophilicity for in vivo brain studies. After radiolabeling with fluorine-18, [18F]11a was used for a dynamic positron emission tomography (PET) study in a rat LPS-induced neuroinflammation model; the inflammatory lesion was clearly visualized with a superior target-to-background ratio compared to [18F]DPA-714. An immunohistochemical examination of the dissected brains confirmed that the uptake location of [18F]11a in the PET study was consistent with a positively activated microglia region. This study proved that [18F]11a could be employed as a potential PET tracer for detecting neuroinflammation and could give possibility for diagnosis of other diseases, such as cancers related with TSPO expression.

Impact of general anaesthesia on endoplasmic reticulum stress: propofol vs. isoflurane.

Background: This study investigated the effects of propofol and isoflurane on endoplasmic reticulum (ER) stress in an animal model under general anaesthesia. Methods: Rats were randomly divided into Propofol and Isoflurane groups. Anaesthesia was maintained with propofol for Propofol group or isoflurane for Isoflurane group during 3 h. ER stress from lymphocytes in blood and tissues was evaluated between two groups after euthanasia. Reactive oxygen species (ROS) from lymphocytes in blood and tissues, and cytokines in blood were also checked. An immunohistochemical assay for ER stress marker from tissues was performed. Results: After anaesthesia, the levels of CCAAT-enhancer-binding protein homologous proteins (CHOP) in blood and liver were significantly higher in Isoflurane group, compared to Propofol group [blood, 31,499 ± 4,934 (30,733, 26,441-38,807) mean fluorescence intensity (MFI) in Isoflurane group vs. 20,595 ± 1,838 (20,780, 18,866-22,232) MFI in Propofol group, p = 0.002; liver, 28,342 ± 5,535 (29,421, 23,388-32,756) MFI in Isoflurane group vs. 20,004 ± 2,155 (19,244, 18,197-22,191) MFI in Propofol group, p = 0.020]. ROS in blood was significantly higher in Isoflurane group, compared to Propofol group. However, cytokines in blood and immunohistochemical assays in tissues were similar between groups. Conclusion: Significant higher of ER stress from blood and liver were observed in rats under anaesthesia with isoflurane, compared to those that received propofol. ROS from blood also showed significant higher under anaesthesia with isoflurane. However, these findings were not associated with any changes in cytokines in blood or immunohistochemical assay in tissues.

Alanine Scanning of YbdZ, an MbtH-like Protein, Reveals Essential Residues for Functional Interactions with Its Nonribosomal Peptide Synthetase Partner EntF.

Nonribosomal peptide synthetases (NRPSs) are megasynthetases that require complex and specific interactions between multiple domains and proteins to functionally produce a metabolite. MbtH-like proteins (MLPs) are integral components of many NRPSs and interact directly with the adenylation domain of the megasynthetases to stimulate functional enzymology. All of the MLP residues that are essential for functional interactions between the MLP and NRPS have yet to be defined. Here we probe the interactions between YbdZ, an MLP, and EntF, an NRPS, from Escherichia coli by performing a complete alanine scan of YbdZ. A phenotypic screen identified 11 YbdZ variants that are unable to replace the wild-type MLP, and these YbdZ variants were characterized using a series of in vivo and in vitro assays in an effort to explain why functional interactions with EntF were disrupted. All of the YbdZ variants enhanced the solubility of overproduced EntF, suggesting they were still capable of direct interactions with the megasynthase. Conversely, we show that EntF also influences the solubility of YbdZ and its variants. In vitro biochemical analyses of EntF function with each of the YbdZ variants found the impact that an amino acid substitution will have on NRPS function is difficult to predict, highlighting the complex interaction between these proteins.

Effect of Equipotent Doses of Propofol versus Sevoflurane Anesthesia on Regulatory T Cells after Breast Cancer Surgery.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Clusters of differentiation 39 and 73, enzymes expressed on the surface of regulatory T cells, promote cancer recurrence and metastasis by suppressing immune cells. The authors hypothesized that propofol is less immunosuppressive than volatile anesthetics. The objective of this randomized trial was to compare the changes in cluster of differentiation 39 and 73 expression on regulatory T cells between propofol- and sevoflurane-based anesthesia during breast cancer surgery. METHODS: A total of 201 patients having breast cancer surgery were randomly assigned and analyzed (n = 99 for propofol, n = 102 for sevoflurane). Blood samples were obtained immediately before anesthesia induction and 1 and 24 h postoperatively. The frequency of cluster of differentiation 39 and 73 expression on circulating regulatory T cells (primary outcome) and the frequency of circulating type 1 and type 17 helper T cells, natural killer cells, and cytotoxic T cells were investigated. Serum cytokines and the neutrophil-to-lymphocyte ratio were also evaluated. RESULTS: Changes in cluster of differentiation 39 and 73 expression on regulatory T cells over time did not differ with propofol and sevoflurane groups (difference [95% confidence interval]: 0.01 [-2.04 to 2.06], P = 0.995 for cluster of differentiation 39; -0.93 [-3.12 to 1.26], P = 0.403 for cluster of differentiation 73). There were no intergroup differences in type 1, type 17 helper T cells, natural killer cells, cytotoxic T cells, cytokines, or the neutrophil-to-lymphocyte ratio. CONCLUSIONS: Changes in immune cells were similar with propofol and sevoflurane during breast cancer surgery. The effect of anesthetics on the perioperative immune activity may be minimal during cancer surgery.