ISRIB plus bortezomib triggers paraptosis in breast cancer cells via enhanced translation and subsequent proteotoxic stress.

Despite the success of proteasome inhibitors (PIs) in treating hematopoietic malignancies, including multiple myeloma (MM), their clinical efficacy is limited in solid tumors. In this study, we investigated the involvement of the integrated stress response (ISR), a central cellular adaptive program that responds to proteostatic defects by tuning protein synthesis rates, in determining the fates of cells treated with PI, bortezomib (Bz). We found that Bz induces ISR, and this can be reversed by ISRIB, a small molecule that restores eIF2B-mediated translation during ISR, in both Bz-sensitive MM cells and Bz-insensitive breast cancer cells. Interestingly, while ISRIB protected MM cells from Bz-induced apoptosis, it enhanced Bz sensitivity in breast cancer cells by inducing paraptosis, the cell death mode that is accompanied by dilation of the endoplasmic reticulum (ER) and mitochondria. Combined treatment with ISRIB and Bz may shift the fate of Bz-insensitive cancer cells toward paraptosis by inducing translational rescue, leading to irresolvable proteotoxic stress.

PSMD14 Targeting Triggers Paraptosis in Breast Cancer Cells by Inducing Proteasome Inhibition and Ca2+ Imbalance.

PSMD14, a subunit of the 19S regulatory particles of the 26S proteasome, was recently identified as a potential prognostic marker and therapeutic target in diverse human cancers. Here, we show that the silencing and pharmacological blockade of PSMD14 in MDA-MB 435S breast cancer cells induce paraptosis, a non-apoptotic cell death mode characterized by extensive vacuolation derived from the endoplasmic reticulum (ER) and mitochondria. The PSMD14 inhibitor, capzimin (CZM), inhibits proteasome activity but differs from the 20S proteasome subunit-inhibiting bortezomib (Bz) in that it does not induce aggresome formation or Nrf1 upregulation, which underlie Bz resistance in cancer cells. In addition to proteasome inhibition, the release of Ca2+ from the ER into the cytosol critically contributes to CZM-induced paraptosis. Induction of paraptosis by targeting PSMD14 may provide an attractive therapeutic strategy against cancer cells resistant to proteasome inhibitors or pro-apoptotic drugs.

Evaluation of the efficacy and safety of conventional and biportal endoscopic decompressive laminectomy in patients with lumbar spinal stenosis (ENDO-B trial): a protocol for a prospective, randomized, assessor-blind, multicenter trial.

BACKGROUND: Recent studies on biportal endoscopic spine surgery in patients with lumbar spinal stenosis have reported good clinical results. However, these studies have been limited by the small sample sizes and use of a retrospective study design. Therefore, we aim to compare the efficacy and safety of biportal endoscopic decompressive laminectomy with those of conventional decompressive laminectomy in a multicenter, prospective, randomized controlled trial. METHODS: This study will include 120 patients (60 per group, aged 20-80 years) with 1- or 2-level lumbar spinal stenosis, who will be recruited from six hospitals. The study will be conducted from July 2021 to December 2024. The primary outcome (Oswestry Disability Index at 12 months after surgery) will be evaluated through a modified intention-to-treat method. The secondary outcomes will include the following: visual analog scale score for low back and lower extremity radiating pain, EuroQol 5-dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scars, and some surgery-related variables. Radiographic outcomes will be analyzed using magnetic resonance imaging or computed tomography. All outcomes will be evaluated before the surgery and at 2 weeks, 3 months, 6 months, and 12 months postoperatively. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for reporting of clinical trial protocols. DISCUSSION: It is hypothesized that the efficacy and safety of biportal endoscopic and conventional decompressive laminectomy will be comparable in patients with lumbar spinal stenosis. The results of this trial will provide a high level of evidence for the efficacy and safety of the biportal endoscopic technique in patients with lumbar spinal stenosis and facilitate the development of clinical practice guidelines. Furthermore, the results of this study may indicate the feasibility of the biportal endoscopic technique for other types of spinal surgery. TRIAL REGISTRATION: The ENDO-B trial is registered at Clinical Research Information Service (CRIS, cris.nih.go.kr ) (KCT0006057; April 52,021).

Osteogenic Effect of Inducible Nitric Oxide Synthase (iNOS)-Loaded Mineralized Nanoparticles on Embryonic Stem Cells.

BACKGROUND/AIMS: This study investigated the effect of inducible nitric oxide synthase-loaded mineralized nanoparticles (iNOS-MNPs) on the osteogenic differentiation of mouse embryonic stem cells (ESCs). METHODS: We prepared iNOS-MNPs using an anionic block copolymer template-mediated calcium carbonate (CaCO3) mineralization process in the presence of iNOS. iNOS-MNPs were spherical and had a narrow size distribution. iNOS was stably loaded within MNPs without denaturation. In order to confirm the successful introduction of iNOS-MNPs into the cytosol of ESCs, intracellular levels of nitric oxide (NO) was determined with a fluorometric analysis. A NO effector molecule, cyclic guanosine 3',5' monophosphate (cGMP) was also quantified with a competitive enzyme immunoassay. Cell viability in response to iNOS-MNP treatment was determined using the cell counting kit-8 (CCK-8) assay. Alkaline phosphatase (ALP) activity assay, intracellular calcium quantification assay, and Alizarin red S staining for matrix mineralization were performed to investigate osteogenic differentiation of ESCs. The protein levels of Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osterix (OSX) as osteogenic-related factors were also assessed by immunofluorescence staining and Western blot analysis. The complex pathways associated with iNOS-MNP-derived osteogenic differentiation of ESCs were evaluated by network-based analysis. RESULTS: Cells with iNOS-MNPs displayed a significant increase in NO and cGMP concentration compared with the control group. When cells were exposed to iNOS-MNPs, there were no adverse effects on cell viability. Importantly, iNOS-MNP uptake promoted the osteogenic differentiation of ESCs. Using transcriptome profiling, we obtained 1,836 differentially-induced genes and performed functional enrichment analysis with ClueGO and KEGG. These analyses identified significantly enriched and interconnected molecular pathways such as protein kinase activity, estrogen receptor activity, bone morphogenetic protein (BMP) receptor binding, ligand-gated ion channel activity, and phosphatidylinositol 3-phosphate binding. CONCLUSION: These findings suggest that iNOS-MNPs can induce osteogenic differentiation in ESCs by integrating complex signaling pathways.

Radiation Dose from Whole-Body F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: Nationwide Survey in Korea.

The purpose of this study was to estimate average radiation exposure from (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) examinations and to analyze possible factors affecting the radiation dose. A nation-wide questionnaire survey was conducted involving all institutions that operate PET/CT scanners in Korea. From the response, radiation doses from injected FDG and CT examination were calculated. A total of 105 PET/CT scanners in 73 institutions were included in the analysis (response rate of 62.4%). The average FDG injected activity was 310 ± 77 MBq and 5.11 ± 1.19 MBq/kg. The average effective dose from FDG was estimated to be 5.89 ± 1.46 mSv. The average CT dose index and dose-length product were 4.60 ± 2.47 mGy and 429.2 ± 227.6 mGy∙cm, which corresponded to 6.26 ± 3.06 mSv. The radiation doses from FDG and CT were significantly lower in case of newer scanners than older ones (P < 0.001). Advanced PET technologies such as time-of-flight acquisition and point-spread function recovery were also related to low radiation dose (P < 0.001). In conclusion, the average radiation dose from FDG PET/CT is estimated to be 12.2 mSv. The radiation dose from FDG PET/CT is reduced with more recent scanners equipped with image-enhancing algorithms.

Antimicrobial activity of cell-free supernatant derived from Ligilactobacillus animalis SWLA-1 in a novel ex vivo canine corneal infection model.

Introduction: Canine bacterial keratitis is a corneal infection that causes various symptoms, including visual impairment, and necessitates eye removal in severe cases. Staphylococcus pseudintermedius is a pathogen that causes significant bacterial keratitis in canine patients. Moreover, multi-drug resistant Staphylococcus pseudintermedius (MDRSP) has been reported in both humans and animals. Regarding treatment failure against multi-drug resistant (MDR) pathogens with classic antibiotics, antimicrobial compounds derived from probiotics have been suggested as an alternative approach. Methods: Ligilactobacillus animalis SWLA-1 strain and its cell-free supernatant (CFS) have previously demonstrated potent antimicrobial activity against various MDR pathogenic bacteria. Based on this finding, we evaluated the anti-staphylococcal activity of CFS derived from Ligilactobacillus animalis SWLA-1 against MDRSP in a newly established ex vivo canine corneal infection model using fresh canine corneoscleral rims. Additionally, an in vitro cytotoxicity test using human keratocytes was performed. Results and Discussion: CFS significantly inhibited the growth of MDRSP in the novel ex vivo model and did not exhibit any significant toxicity against keratocytes in vitro. Based on these results, the antimicrobial compounds in CFS show potential as a novel approach for MDR staphylococcal keratitis treatment.

Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis.

Valosin-containing protein (VCP)/p97, an AAA+ ATPase critical for maintaining proteostasis, emerges as a promising target for cancer therapy. This study reveals that targeting VCP selectively eliminates breast cancer cells while sparing non-transformed cells by inducing paraptosis, a non-apoptotic cell death mechanism characterized by endoplasmic reticulum and mitochondria dilation. Intriguingly, oncogenic HRas sensitizes non-transformed cells to VCP inhibition-mediated paraptosis. The susceptibility of cancer cells to VCP inhibition is attributed to the non-attenuation and recovery of protein synthesis under proteotoxic stress. Mechanistically, mTORC2/Akt activation and eIF3d-dependent translation contribute to translational rebound and amplification of proteotoxic stress. Furthermore, the ATF4/DDIT4 axis augments VCP inhibition-mediated paraptosis by activating Akt. Given that hyperactive Akt counteracts chemotherapeutic-induced apoptosis, VCP inhibition presents a promising therapeutic avenue to exploit Akt-associated vulnerabilities in cancer cells by triggering paraptosis while safeguarding normal cells.

Quantitative Comparison of Vertebral Structural Changes After Percutaneous Vertebroplasty Between Unilateral Extrapedicular Approach and Bilateral Transpedicular Approach Using Voxel-Based Morphometry.

OBJECTIVE: To compare unilateral extrapedicular vertebroplasty (UEV) and bilateral transpedicular vertebroplasty (BTV) by quantitatively calculating the structural changes of fractured vertebral body after percutaneous vertebroplasty (PVP) using 3-dimensional voxel-based morphometry (VBM). METHODS: We calculated bone cement volume (BCV); vertebral body volume (VBV); leaked intradiscal BCV; and spatial, symmetric, and even bone cement distribution (BCD) in and out of 222 vertebral bodies treated with 2 different PVPs using VBM and evaluated the incidence of subsequent vertebral compression fracture (SVCF). Statistical analyses were conducted to compare values between the 2 different PVPs. RESULTS: Relative BCV, which is a potential risk factor for SVCF, was higher in the BTV group based on the data using VBM (0.22±0.03 vs. 0.29±0.03; p<0.001, t-test); however, the SVCF incidence between the 2 surgeries was not significantly different (UEV, 24.7%; BTV, 31%; p=0.046, chi-square test). Spatial, even, and symmetric BCD along the 3 axes was not significantly different between UEV and BTV using VBM (x, y, z-axis, p=0.893, p= 0.590, p=0.908 respectively, chi-square test). CONCLUSION: Contrary to intuitive concerns, UEV can inject a sufficient and more optimal BCV than BTV. Additionally, it can inject bone cement spatially, symmetrically, and evenly well-distributed without an increased rate of intradiscal leakage and SVCF compared with BTV based on VBM. Therefore, UEV could be a superior alternative surgical method with similar clinical effectiveness and safety, considering the above results and the consensus that UEV is less invasive.

Antimicrobial Activity of Ligilactobacillus animalis SWLA-1 and Its Cell-Free Supernatant against Multidrug-Resistant Bacteria and Its Potential Use as an Alternative to Antimicrobial Agents.

The emergence of multidrug-resistant (MDR) bacteria and the spread of antimicrobial resistance among various bacteria are major threats to the global community. Due to the increased failure of classical antibiotic treatments against MDR bacterial infections, probiotics and their antimicrobial compounds have been suggested as promising alternatives to deal with MDR bacteria. Various strains of lactic acid bacteria have been reported to produce antagonistic molecules against pathogens. A new strain of Ligilactobacillus animalis, L. animalis SWLA-1, isolated from the feces of healthy dogs, shows strong antimicrobial activity against not only common pathogens but also MDR bacteria. In this study, we compared the antimicrobial activity of L. animalis SWLA-1 with that of other lactobacilli and antibiotics using an agar spot assay. Additionally, a novel spot inhibition index was developed and validated to quantitively evaluate the inhibitory activities of lactobacilli and antibiotics. A competitive coculture assay of L. animalis SWLA-1 with MDR bacteria further demonstrated its antibacterial activity. Furthermore, we evaluated the antimicrobial activity of the cell-free supernatant (CFS) of L. animalis SWLA-1 and its stability under various conditions in vitro. We found that L. animalis SWLA-1 and its CFS are potential alternatives to classic antimicrobial agents.

Anti-Staphylococcal Activity of Ligilactobacillus animalis SWLA-1 and Its Supernatant against Multidrug-Resistant Staphylococcus pseudintermedius in Novel Rat Model of Acute Osteomyelitis.

Osteomyelitis caused by staphylococcal infection is a serious complication of orthopedic surgery. Staphylococcus pseudintermedius is the main causative agent of osteomyelitis in veterinary medicine. Methicillin-resistant S. pseudintermedius (MRSP) has been reported in companion animals, especially dogs. Multidrug-resistant S. pseudintermedius is an emerging pathogen and has acquired antibiotic resistance against various commercial antimicrobial agents. New antimicrobial compounds are urgently needed to address antibiotic resistance, and the development of novel agents has become an international research hotspot in recent decades. Antimicrobial compounds derived from probiotics, such as bacteriocins, are promising alternatives to classical antibiotics. In this study, the antibacterial activities of Ligilactobacillus animalis SWLA-1 and its concentrated cell-free supernatant (CCFS) were evaluated in vitro and in vivo. The CCFS of this bacterium showed no toxicity against osteoblast and myoblast cells in vitro, while significantly inhibiting the multidrug-resistant S. pseudintermedius KUVM1701GC strain in a newly established rat model. The CCFS significantly inhibited multidrug-resistant staphylococci both in vitro and in vivo. This suggests that CCFS derived from L. animalis SWLA-1 has potential as an alternative to classic antibiotics for staphylococcal infections in dogs.

Characteristics of a Temperature-Sensitive Mutant Strain of Salmonella Enteritidis and Its Potential as a Live Vaccine Candidate.

Salmonella Enteritidis is a common foodborne pathogen transmitted through poultry products, which are its main carriers. Poultry are vaccinated against Salmonella Enteritidis in many countries, despite the absence of clinical symptoms, using commercially available live-attenuated vaccines. We previously constructed a highly attenuated temperature-sensitive (ts) Salmonella Enteritidis mutant, 2S-G10. In the present study, we describe the construction and attenuation-associated characteristics of 2S-G10. We infected 1-day-old chicks with 2S-G10 and the parental strains to evaluate the attenuation. One week after infection, 2S-G10 was not detected in the liver, cecum, or cecal tonsil tissues of the orally inoculated chicks, contrary to the parental strain. This indicates that 2S-G10 was highly attenuated when compared to the parental stain. In vitro experiments revealed the inability of 2S-G10 to grow at the normal body temperature of chickens and invade chicken liver epithelial cells. Moreover, single nucleotide polymorphism (SNP) analysis between the complete genome sequence of 2S-G10 and its parental strain revealed SNPs in bcsE, recG, rfaF, and pepD_1 genes, which are involved in epithelial cell invasion and persistence in host systems, growth, lipopolysaccharide core biosynthesis, and cellular survival under heat stress, respectively. These potential characteristics are consistent with the findings of in vitro experiments. Conclusively, chemical treatment-induced random genetic mutations highly attenuated 2S-G10, implying its potential to be developed as a novel live-attenuated vaccine against Salmonella Enteritidis.

Evaluation of the efficacy and safety of conventional and interlaminar full-endoscopic decompressive laminectomy to treat lumbar spinal stenosis (ENDO-F trial): Protocol for a prospective, randomized, multicenter trial.

Lumbar spinal stenosis is a common spinal degenerative condition. Minimally invasive interlaminar full-endoscopic decompressive laminectomy provides greater patient satisfaction and faster recovery than open decompressive laminectomy. The aim of our randomized controlled trial will be to compare the safety and efficacy of interlaminar full-endoscopic laminectomy and open decompressive laminectomy. Our trial will include 120 participants (60 per group) who will undergo surgical treatment for lumbar spinal stenosis. The primary outcome will be the Oswestry Disability Index measured at 12 months postoperatively. Secondary patient-reported outcomes will include back and radicular leg pain measured via a visual analog scale; the Oswestry Disability Index; the Euro-QOL-5 Dimensions score measured at 2 weeks and at 3, 6, and 12 months postoperatively; and patient satisfaction. The functional measures will include time to return to daily activities postoperatively and walking distance/time. The surgical outcomes will include postoperative drainage, operation time, duration of hospital stay, postoperative creatine kinase (an indicator of muscle injury) level, and postoperative surgical scarring. Magnetic resonance and computed tomography images and simple radiographs will be obtained for all patients. The safety outcomes will include surgery-related complications and adverse effects. All evaluations will be performed by a single assessor at each participating hospital who will be blinded to group allocation. The evaluations will be conducted preoperatively and at 2 weeks and 3, 6, and 12 months postoperatively. The randomized, multicenter design of the trial, blinding, and justification of the sample size will reduce the risk of bias in our trial. The results of the trial will provide data regarding the use of interlaminar full-endoscopic laminectomy as an alternative to open decompressive laminectomy that results in similar surgical findings with less invasiveness. Trial registration: This trial is registered at cris.nih.go.kr. (KCT0006198; protocol version 1; 27 May 2021).

Antimicrobial activity of dominant Ligilactobacillus animalis strains in healthy canine feces and their probiotic potential.

The number of companion animals living with humans has continually increased over the last few decades, and so has the interest of owners and stakeholders in the animal food and probiotics industry. Currently, the probiotic bacteria added to the feed of companion animals predominantly originate from the lactic acid bacteria (LAB) used for humans; however, there are differences between the microbiota of humans and that of their companion animals. This study aimed to determine the dominant LAB in dog feces and investigate their functional properties. Ligilactobacillus animalis (formerly called Lactobacillus animalis) was identified as the dominant lactic acid bacterium in dog feces. It displayed various inhibitory effects against pathogenic and enteropathogenic bacteria. This finding suggests that Ligilactobacillus animalis can potentially be used in novel probiotics or as a food additive for dogs.

Copper arsenite-complexed Fenton-like nanoparticles as oxidative stress-amplifying anticancer agents.

We report copper(II) arsenite (CuAS)-integrated polymer micelles (CuAS-PMs) as a new class of Fenton-like catalytic nanosystem that can display reactive oxygen species (ROS)-manipulating anticancer therapeutic activity. CuAS-PMs were fabricated through metal-catechol chelation-based formation of the CuAS complex on the core domain of poly (ethylene glycol)-b-poly(3,4-dihydroxy-L-phenylalanine) (PEG-PDOPA) copolymer micelles. CuAS-PMs maintained structural robustness under serum conditions. The insoluble state of the CuAS complex was effectively retained at physiological pH, whereas, at endosomal pH, the CuAS complex was ionized to release arsenite and cuprous Fenton catalysts (Cu+ ions). Upon endocytosis, CuAS-PMs simultaneously released hydrogen peroxide (H2O2)-generating arsenite and Fenton-like reaction-catalyzing Cu+ ions in cancer cells, which synergistically elevated the level of highly cytotoxic hydroxyl radicals (•OH), thereby preferentially killing cancer cells. Animal experiments demonstrated that CuAS-PMs could effectively suppress the growth of solid tumors without systemic in vivo toxicity. The design rationale of CuAS-PMs may provide a promising strategy to develop diverse oxidative stress-amplifying agents with great potential in cancer-specific therapy.

Evaluation of Immune Responses and Protective Efficacy of a Novel Live Attenuated Salmonella Enteritidis Vaccine Candidate in Chickens.

An ideal vaccine for controlling Salmonella infection in chicken flocks should be safe, inducing both humoral and cellular immunity. Live attenuated vaccines against Salmonella Enteritidis (S. Enteritidis) have been used as a potential control method of Salmonella infection in the poultry industry. However, live attenuated vaccines can persistently infect poultry for long periods and can become virulent revertant strains. In this study, we assessed the immune responses and protective efficacy of a temperature-sensitive attenuated S. Enteritidis mutant as a potential vaccine candidate. In addition, we evaluated the combined vaccine administration methods to maximize both humoral and cellular immune responses in chickens induced by the vaccine candidate. Immune responses and protective efficacy were compared between the Oral/IM group, vaccinated using one oral dose at four weeks old and a booster intramuscular dose at seven weeks old, and the IM/Oral group, vaccinated using one intramuscular dose at four weeks old and a booster oral dose at seven weeks old. The Oral/IM group showed stronger immune responses than those of the IM/Oral group. Spleens from the Oral/IM group showed a promising tendency of reduction of challenged Salmonella compared with those of other groups. Overall, the results indicated that the S. Enteritidis mutant strain is a promising live attenuated vaccine candidate with good efficacy.

Comparing the efficacy and safety of minimally invasive biportal endoscopic spine surgery versus conventional microscopic discectomy in single-level lumbar herniated intervertebral disc (ENDO-BH Trial): a multicenter, prospective, randomized controlled equivalence trial study protocol.

BACKGROUND: Biportal endoscopic surgery has recently been performed in lumbar discectomy, with advantages over conventional surgery, such as less skin scarring and muscle damage. However, the clinical results have not been established. Although previous studies reported no difference between the biportal endoscopic and microscopic discectomy clinical results, the evidence was weak. Therefore, this study aims to evaluate the efficacy and safety of the biportal endoscopic discectomy versus the microscopic discectomy. METHODS: This prospective multicenter randomized controlled equivalence trial is designed to compare the efficacy and safety outcomes of patients who underwent lumbar discectomy using biportal endoscopy or microscopy. We will include 100 participants (50 per group) with a lumbar herniated disc. The primary outcome will be the Oswestry Disability Index (ODI) score 12 months after surgery based on a modified intention-to-treat strategy. The secondary outcomes will include the visual analog scale score for low back and lower extremity radiating pain, the ODI score, the Euro-Qol-5-Dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scar, and surgery-related variables, such as postoperative drainage, operation time, admission duration, postoperative creatine kinase, and implementation status of conversion to open surgery. Radiographic outcomes will also be analyzed using magnetic resonance imaging (MRI) or computed tomography (CT) and simple radiographs. Safety will be assessed by evaluating all adverse and severe adverse events and surgery-related effects. The participants will be assessed by a blinded assessor before surgery (baseline) and 2 weeks and 3, 6, and 12 months after surgery. DISCUSSION: This trial will be the first prospective, multicenter, randomized controlled trial to analyze the efficacy and safety of biportal endoscopic discectomy in lumbar herniated disc. This trial is designed for evaluating the equivalence of the results between biportal endoscopic and microscopic discectomy including adequate sample size, blinded analyses, and prospective registration to reduce bias. This trial will provide enough data on the effectiveness and safety of biportal endoscopic surgery and will be an important study that allows clear conclusions. TRIAL REGISTRATION: Clinical Research Information Service (cris.nih.go.kr.) ( KCT0006191 ). Registered on 27 March 2021.

Comparative study of the efficacy and safety of minimally invasive interlaminar full-endoscopic discectomy versus conventional microscopic discectomy in single-level lumbar herniated intervertebral disc (ENDO-F Trial): a multicenter, prospective, randomized controlled trial protocol.

BACKGROUND: Advances in minimally invasive surgery have expanded the indications for interlaminar full-endoscopic discectomy. Although the clinical outcomes for this approach may be equivalent to those of conventional microscopic discectomy, the supporting evidence is still based on small, single-center, prospective, and retrospective studies. Therefore, a multicenter randomized controlled trial is warranted. METHODS: This will be a prospective, multicenter, randomized controlled trial comparing the efficacy and safety of interlaminar full-endoscopic discectomy to those of conventional microscopic discectomy. The trial will enroll 100 participants with a lumbar disc herniation, 50 in each group. The primary outcome will be the Oswestry Disability Index (ODI) score at 12 months post-surgery. Secondary outcomes will be back and leg pain (visual analog scale); the ODI; the EuroQol-5-dimension score; patient satisfaction; and walking distance/time and time to return to daily activities post-surgery. Surgical outcomes will include postoperative drainage, operative time, duration of hospital stay, postoperative creatine kinase level as an indicator of muscle injury, and postoperative scarring. Postoperative magnetic resonance imaging, computed tomography, and simple radiography will be performed to evaluate radiographic outcomes between the two surgical approaches. Surgery-related complications and adverse effects will be evaluated as safety outcomes. A single assessor at each participating hospital, blinded to group allocation, will assess the enrolled participants at baseline, at 2 weeks, and at 3, 6, and 12 months postoperatively. DISCUSSION: This trial is designed to determine whether interlaminar full-endoscopic discectomy is clinically comparable to microscopic discectomy to treat lumbar disc herniations. All efforts will be made to reduce bias, including adequate sample size, blinded analyses, and multicenter prospective registration. The outcomes will inform practice, providing the evidence needed for using interlaminar full-endoscopic over microscopic discectomy by confirming the potential of this technique to improve patient satisfaction and clinical outcomes. TRIAL REGISTRATION: Clinical Research Information Service; cris.nih.go.kr. (KCT0006277); protocol version (v1, June 8, 2021).

Ketal cross-linked poly(ethylene glycol)-poly(amino acid)s copolymer micelles for efficient intracellular delivery of doxorubicin.

A biocompatible, robust polymer micelle bearing pH-hydrolyzable shell cross-links was developed for efficient intracellular delivery of doxorubicin (DOX). The rationally designed triblock copolymer of poly(ethylene glycol)-poly(L-aspartic acid)-poly(L-phenylalanine) (PEG-PAsp-PPhe) self-assembled to form polymer micelles with three distinct domains of the PEG outer corona, the PAsp middle shell, and the PPhe inner core. Shell cross-linking was performed by the reaction of ketal-containing cross-linkers with Asp moieties in the middle shells. The shell cross-linking did not change the micelle size and the spherical morphology. Fluorescence quenching experiments confirmed the formation of shell cross-linked diffusion barrier, as judged by the reduced Stern-Volmer quenching constant (K(SV)). Dynamic light scattering and fluorescence spectroscopy experiments showed that shell cross-linking improved the micellar physical stability even in the presence of micelle disrupting surfactants, sodium dodecyl sulfate (SDS). The hydrolysis kinetics study showed that the hydrolysis half-life (t(1/2)) of ketal cross-links was estimated to be 52 h at pH 7.4, whereas 0.7 h at pH 5.0, indicating the 74-fold faster hydrolysis at endosomal pH. Ketal cross-linked micelles showed the rapid DOX release at endosomal pH, compared to physiological pH. Confocal laser scanning microscopy (CLSM) showed that ketal cross-linked micelles were taken up by the MCF-7 breast cancer cells via endocytosis and transferred into endosomes to hydrolyze the cross-links by lowered pH and finally facilitate the DOX release to inhibit proliferation of cancer cells. This ketal cross-linked polymer micelle is promising for enhanced intracellular delivery efficiency of many hydrophobic anticancer drugs.

Whole-Genome Analysis of Multidrug-Resistant Salmonella Enteritidis Strains Isolated from Poultry Sources in Korea.

The Salmonella Enterica subsp. Enterica serovar Enteritidis is one of main serovars isolated from human patients with food poisoning and poultry without clinical signs. Consumption of poultry products contaminated with Salmonella Enteritidis is a common source of human salmonellosis; 82 Salmonella spp. were isolated from 291 samples of retail chicken meat, 201 one-day-old chicks, 30 internal organs of chickens, 156 chicken eggs, 100 duck eggs, 38 straw bedding samples, 18 samples of retail duck meat, and 19 swab samples from slaughterhouses in 2019 and 2020. An antibiotic susceptibility test was performed for all isolates, revealing 33 multidrug-resistant (MDR) strains. The whole genome of 33 MDR strains isolated in 2019 and 2020 and 10 strains isolated in 2011, 2012, and 2017 was sequenced using the MinION sequencing protocol. Within these 43 samples, 5 serovars were identified: S. Enteritidis, S. Agona, S. Virchow, S. Albany, and S. Bareilly. The most common serovar was S. Enteritidis (26/43), which showed the highest resistance to ampicillin (100%), followed by nalidixic acid (90%) and colistin (83%). Core genome multilocus sequence typing analysis showed that the S. Enteritidis strains isolated from different sources and in different years were clustered together. In addition, the S. Enteritidis strains isolated since 2011 consistently harbored the same antibiotic resistance patterns.

Complete Genome Sequence of Mycoplasma gallisepticum Strain KUVMG001, an Isolate from South Korea.

Mycoplasma gallisepticum causes chronic respiratory diseases in poultry and economic losses to the chicken and turkey industry. We report the complete genome sequence of the field isolate strain KUVMG001 of Mycoplasma gallisepticum from South Korea.