Efficacy and safety of biosimilar trastuzumab (CT-P6) in routine clinical practice in the Republic of Korea: a real-world post-marketing surveillance study.

BACKGROUND: The trastuzumab biosimilar CT-P6 is approved for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), metastatic breast cancer (MBC), and metastatic gastric cancer (MGC). The objective of this post-marketing surveillance (PMS) study was to evaluate the real-world safety and effectiveness of CT-P6 in patients with HER2-positive cancers. RESEARCH DESIGN AND METHODS: This open-label, observational, prospective, PMS study collected data via investigator surveys from 35 centers in the Republic of Korea (5 October 2018-4 October 2022). Eligible patients with HER2-positive EBC, MBC, or MGC started CT-P6 treatment during routine clinical practice, followed by 1-year observation. Evaluations included adverse events (AEs), adverse drug reactions (ADRs), and effectiveness. RESULTS: Safety was analyzed in 642 patients (494 EBC, 94 MBC, 54 MGC). Overall, 325 (50.6%) patients experienced 1316 AEs, and 550 ADRs occurred in 199 (31.0%) patients. Unexpected ADRs occurred in 62 (9.7%) patients. Unexpected ADRs and ADRs of special interest did not raise any new safety signals. Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response. CONCLUSIONS: In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies.

The Effects of Fermented Rice Drink With Lactiplantibacillus plantarum JSA22 in Overweight Irritable Bowel Syndrome Patients: A Randomized, Double-blind, Placebo-controlled Study.

Background/Aims: This study aims to investigate the effect of a fermented rice drink with Lactiplantibacillus plantarum JSA22 on symptoms, blood tests, microbiomes, and fecal metabolites in patients with irritable bowel syndrome (IBS) who were overweight. Methods: Sixty overweight (body mass index ≥ 23 kg/m2) patients aged between 20 and 65 with IBS were enrolled. Patients were divided into 2 groups and administered either a fermented rice drink or an nonfermented rice drink for a month. The symptom questionnaire, blood samples, and stool samples for microbiome and metabolite were collected before and after the month of rice drink administration. The primary efficacy variable was the subject's global assessment of IBS symptoms. Results: In both groups, global IBS symptoms, including abdominal pain, bowel habit, urgency, and abdominal distension, improved significantly (P < 0.01). The abdominal bloating was more significantly improved in the fermented rice drink group than in the nonfermented rice drink group (P < 0.05). Significant changes were not observed in metabolic syndrome-related blood tests or fecal metabolites in either group. However, microbiome analysis showed significant differences in genus levels before and after consuming fermented rice drink, such as in Blautia in stool (P = 0.020) and Prevotella (P = 0.017) and Oribacterium (P = 0.018) in saliva. Conclusions: The fermented rice drink with L. plantarum JSA22 showed a beneficial effect in reducing abdominal distension in IBS patients. Bacteria that reduce visceral fat accumulation increased in the stool and saliva of patients who consumed fermented rice drinks.

Masculinity, Rather Than Biological Sex, Is Associated With Psychological Comorbidities in Patients With Irritable Bowel Syndrome.

Background/Aims: Irritable bowel syndrome (IBS) generally shows sex differences, and psychiatric comorbidities play an important role in its pathogenesis. We aim to measure the levels of gender roles and investigate their relationship with psychiatric factors in patients with IBS versus healthy controls. Methods: Patients diagnosed with IBS by Rome III and whose colonoscopy findings were normal were enrolled at multiple sites in Korea. The participants completed the Korean Sex Role Inventory-Short Form (KSRI-SF) to assess masculinity and femininity, the stress questionnaire, the Hospital Anxiety Depression Scale (HADS), and the 36-item Short Form Health Survey questionnaire to assess the quality of life (QOL). Results: In total, 102 patients with IBS (male:female = 35:67; mean age 42.6 ± 16.7 years) and 55 controls (male:female = 20:35; mean age 42.4 ± 11.1 years) were recruited. IBS patients had higher stress (9.69 ± 8.23 vs 4.56 ± 8.31, P < 0.001) and HADS scores (16.12 ± 7.17 vs 10.22 ± 5.74, P < 0.001) than the control group, but showed no significant difference in KSRI-SF scores. No significant differences in HADS and KSRI-SF scores were found between males and females. However, IBS patients whose symptoms worsened due to stress and patients with anxiety or depression had significantly lower masculinity. QOL was poorer in IBS patients than in controls. In stepwise multivariate analyses, the anxiety score, depression score, and the degree of daily life disturbance, not masculinity, were associated with the QOL of IBS patients. Conclusions: IBS patients had higher stress, more psychiatric comorbidities, and lower QOL than controls. Low masculinity, rather than sex, was associated with stress and psychological comorbidities, which deteriorated the QOL in IBS patients.

Efficacy and safety of CKD-495 in acute and chronic gastritis: A Phase III superiority clinical trial.

BACKGROUND: Despite the availability of numerous treatment options, many patients with gastritis experience only partial symptom relief. CKD-495, a newly developed product with the active ingredient extracted from Cinnamomum cassia Presl., has demonstrated anti-inflammatory and antioxidant activity in vitro and an in vivo protective effect against gastric damage by stimulating mucus secretion. This study compared the efficacy and safety of CKD-495 with Artemisiae argyi folium (AAF) for the treatment of acute and chronic gastritis. AAF, a gastric mucosa protective agent that promotes gastric mucosa regeneration, has been used clinically for about 20 years. METHODS: This phase III multicenter, randomized, double-blind, parallel-group trial (ClinicalTrials.gov; NCT04255589) assigned 242 patients with endoscopically-proven gastric mucosal erosions to receive CKD-495 75 mg (n = 122) or AAF 60 mg (n = 120), respectively, with placebo (for double-blind purposes) 3 times a day for 2 weeks. The primary efficacy endpoint was the erosion improvement rate. Secondary endpoints included erosion cure rates, and improvement rates for edema, redness, hemorrhage, and gastrointestinal (GI) symptoms. Drug-related adverse events were evaluated. RESULTS: The erosion improvement rate was significantly higher in the CKD-495 group than in the AAF group for both the full analysis set (55.9% vs 39.4%, P = .0063) and per-protocol set (54.6% vs 38.2%, P = .0084). In addition, the erosion improvement rate in patients with acute or chronic gastritis showed that the CKD-495 group had better improvement of erosion than the AAF group, especially in patients with chronic gastritis. Analysis of secondary endpoints, which included erosion cure rate and the improvement rates of edema, redness, hemorrhage, and GI symptoms, showed that the CKD-495 group was more effective than the AAF group. There were no significant between-group differences in safety profiles. No serious adverse events or adverse drug reactions occurred. CONCLUSIONS: These results demonstrate that CKD-495 75 mg is superior to AAF 60 mg in terms of the endoscopic improvement rate of erosions in patients with acute or chronic gastritis. This new mucoprotective agent, CKD-495, can be considered the therapy of choice for symptomatic relief and healing of gastritis.

Catalytic hydrolysis of agar using magnetic nanoparticles: optimization and characterization.

BACKGROUND: Agar is used as a gelling agent that possesses a variety of biological properties; it consists of the polysaccharides agarose and porphyrin. In addition, the monomeric sugars generated after agar hydrolysis can be functionalized for use in biorefineries and biofuel production. The main objective of this study was to develop a sustainable agar hydrolysis process for bioethanol production using nanotechnology. Peroxidase-mimicking Fe3O4-MNPs were applied for agar degradation to generate agar hydrolysate-soluble fractions amenable to Saccharomyces cerevisiae and Escherichia coli during fermentation. RESULTS: Fe3O4-MNP-treated (Fe3O4-MNPs, 1 g/L) agar exhibited 0.903 g/L of reducing sugar, which was 21-fold higher than that of the control (without Fe3O4-MNP-treated). Approximately 0.0181% and 0.0042% of ethanol from 1% of agar was achieved using Saccharomyces cerevisiae and Escherichia coli, respectively, after process optimization. Furthermore, different analytical techniques (FTIR, SEM, TEM, EDS, XRD, and TGA) were applied to validate the efficiency of Fe3O4-MNPs in agar degradation. CONCLUSIONS: To the best of our knowledge, Fe3O4-MNP-treated agar degradation for bioethanol production through process optimization is a simpler, easier, and novel method for commercialization.

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Safety tests and clinical research on buccal and nasal microneedle swabs for genomic analysis.

Conventional swabs have been used as a non-invasive method to obtain samples for DNA analysis from the buccal and the nasal mucosa. However, swabs may not always collect pure enough genetic material. In this study, buccal and nasal microneedle swab is developed to improve the accuracy and reliability of genomic analysis. A cytotoxicity test, a skin sensitivity test, and a skin irritation test are conducted with microneedle swabs. Polymer microneedle swabs meet the safety requirements for clinical research and commercial use. When buccal and nasal microneedle swabs are used, the amount of genetic material obtained is greater than that from commercially available swabs, and DNA purity is also high. The comparatively short microneedle swab (250 µm long) cause almost no pain to all 25 participants. All participants also report that the microneedle swabs are very easy to use. When genotypes are compared at five SNP loci from blood of a participant and from that person's buccal or nasal microneedle swab, the buccal and nasal microneedle swabs show 100% concordance for all five SNP genotypes. Microneedle swabs can be effectively used for genomic analysis and prevention through genomic analysis, so the utilization of microneedle swabs is expected to be high.

On-demand Versus Continuous Maintenance Treatment With a Proton Pump Inhibitor for Mild Gastroesophageal Reflux Disease: A Prospective Randomized Multicenter Study.

Background/Aims: It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD). We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. Methods: Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals. Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. Results: A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the non-inferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. Conclusions: Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

Is conservative treatment (enucleation using modified Carnoy's solution) of odontogenic keratocyst in the maxilla good prognosis?

Odontogenic keratocysts (OKCs) located in the maxillae have rarely been reported in the literature. Standard treatment modalities for OKC range from marsupialization to marginal resection. However, most of the studies on OKC treatment have been related to mandibular OKCs. The anatomical structure and loose bone density of the maxillae and the empty space of the maxillary sinus could allow rapid growth of a lesion and the ability to tolerate tumor occupancy in the entire maxilla within a short period of time. Therefore, OKCs of the maxillae require more aggressive surgery, such as resection. As an alternative, this report introduces a modified Carnoy's solution, a strong acid, as an adjuvant chemotherapy after cyst enucleation. This report describes the clinical outcomes of enucleation using a modified Carnoy's solution in patients with large OKCs on the posterior maxillae. In three cases, application of a modified Carnoy's solution had few side effects or morbidity. Each patient was followed for four to six years, and none showed any signs of recurrence. In conclusion, adjuvant treatment with a modified Carnoy's solution can be considered a treatment option capable of reducing the recurrence rate of OKC in the maxillae.

Dual-frequency piezoelectric micromachined ultrasound transducer based on polarization switching in ferroelectric thin films.

Due to its additional frequency response, dual-frequency ultrasound has advantages over conventional ultrasound, which operates at a specific frequency band. Moreover, a tunable frequency from a single transducer enables sonographers to achieve ultrasound images with a large detection area and high resolution. This facilitates the availability of more advanced techniques that simultaneously require low- and high-frequency ultrasounds, such as harmonic imaging and image-guided therapy. In this study, we present a novel method for dual-frequency ultrasound generation from a ferroelectric piezoelectric micromachined ultrasound transducer (PMUT). Uniformly designed transducer arrays can be used for both deep low-resolution imaging and shallow high-resolution imaging. To switch the ultrasound frequency, the only requirement is to tune a DC bias to control the polarization state of the ferroelectric film. Flextensional vibration of the PMUT membrane strongly depends on the polarization state, producing low- and high-frequency ultrasounds from a single excitation frequency. This strategy for dual-frequency ultrasounds meets the requirement for either multielectrode configurations or heterodesigned elements, which are integrated into an array. Consequently, this technique significantly reduces the design complexity of transducer arrays and their associated driving circuits.

Cell-free protein synthesis system: A new frontier for sustainable biotechnology-based products.

Cell-free protein synthesis (CFPS) system is an innovative technology with a wide range of potential applications that could challenge current thinking and provide solutions to environmental and health issues. CFPS system has been demonstrated to be a successful way of producing biomolecules in a variety of applications, including the biomedical industry. Although there are still obstacles to overcome, its ease of use, versatility, and capacity for integration with other technologies open the door for it to continue serving as a vital instrument in synthetic biology research and industry. In this review, we mainly focus on the cell-free based platform for various product productions. Moreover, the challenges in the bio-therapeutic aspect using cell-free systems and their future prospective for the improvement and sustainability of the cell free systems.

Comparison of complications after closure of totally implantable venous access devices with non-absorbable suture and n-butyl-2-cyanoacrylate (NBCA) skin adhesive: Propensity score matching analysis.

PURPOSE: This study aimed to compare the complication rates of non-absorbable suture (NAS) and n-butyl-2-cyanoacrylate (NBCA) skin adhesive for skin closure during totally implantable venous access devices (TIVADs) implantation. METHODS: Between March 2020 and February 2021, 586 consecutive patients who underwent TIVAD implantation were retrospectively analyzed. Two groups of patients suture with NAS (n = 299) or NBCA (n = 287) were followed up for 18 months to compare the occurrence of infection, thrombosis, and non-thrombotic malfunction. A total of 364 cases were extracted using propensity score matching in a 1:1 ratio. Mean TIVADs maintenance days were analyzed using Kaplan-Meier survival analysis. RESULTS: Nineteen cases of complications occurred (0.294/1000 catheter-days) in the NAS group and 17 cases (0.210/1000 catheter-days) in the NBCA group. The difference in the complication rates between the two groups was not statistically significant (p = 0.725) after propensity score matching. Mean TIVADs maintenance days were 627.3 days in NAS group and 697.6 days in NBCA group. There was no statistically significant difference in the number of TIVADs maintenance days between the two groups (p = 0.081). CONCLUSION: In TIVADs implantation, skin closure using NBCA showed no difference in the occurrence of infectious complications compared with conventional non-absorbable skin suture.

Impact of proton pump inhibitors on the risk of small bowel or colorectal bleeding: A systematic review and meta-analysis.

BACKGROUND: Several studies have suggested that the mucosal protective effects of proton pump inhibitors (PPIs) do not extend beyond the duodenum; however, PPIs may cause lower gastrointestinal (LGI) injury, although these relationships have not yet been fully elucidated. METHODS: We searched all the relevant studies published until September 2022 that examined the risk of PPIs for LGI bleeding. We performed a meta-analysis of the risk of LGI bleeding (small bowel (SB) or colorectal bleeding) between PPI users and non-users. A subgroup analysis of patients consuming aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) was also performed. RESULTS: Twelve studies with 341,063 participants were included in this meta-analysis. The use of PPIs was associated with the risk of LGI bleeding (odds ratio [OR] [95% confidence interval [CI]] = 1.42 [1.16-1.73]; hazard ratio [HR] [95% CI] = 3.23 [1.56-6.71]). An association between PPI use and the risk of LGI bleeding was also identified in the subgroup of aspirin or NSAID users (OR [95% CI] = 1.64 [1.49-1.80]; HR [95% CI] = 6.55 [2.01-21.33]). In the bleeding site-specific analyses, the risk of SB bleeding was associated with PPI use (OR [95% CI] = 1.54 [1.30-1.84]). CONCLUSIONS: PPI use was associated with an increased risk of LGI bleeding, particularly SB bleeding. This association was particularly pronounced among aspirin and NSAID users. Inappropriate PPI prescriptions should be avoided in patients with LGI bleeding and a low risk of upper gastrointestinal disease.

Comparative Efficacy of Tegoprazan vs Esomeprazole/Sodium Bicarbonate for the Treatment of Helicobacter pylori Infection.

INTRODUCTION: Potassium-competitive acid blockers and proton pump inhibitors/sodium bicarbonate can rapidly increase intragastric pH. In this study, we aimed to compare the clinical outcomes of tegoprazan-based and esomeprazole/sodium bicarbonate-based triple therapies in the treatment of Helicobacter pylori infection. METHODS: We retrospectively reviewed the data of patients with H. pylori infection treated with a 14-day tegoprazan-based triple therapy or 14-day esomeprazole/sodium bicarbonate-based triple therapy. The primary end point was the H. pylori eradication rate with first-line treatment in an intention-to-treat analysis. Secondary end points included the eradication rate with first-line therapy in the per-protocol analysis and adverse events associated with eradication therapy. RESULTS: Of the 854 included patients, 435 were treated with tegoprazan-based therapy, and 419 received esomeprazole/sodium bicarbonate-based therapy. In the intention-to-treat population, no significant difference in eradication rate was detected between the tegoprazan-treated and esomeprazole/sodium bicarbonate-treated groups (78.6% [95% confidence interval (CI), 74.6-82.3%] vs 81.4% [95% CI, 77.4-84.9%], P = 0.313). The per-protocol analysis also revealed a similar eradication rate between groups (tegoprazan vs esomeprazole/sodium bicarbonate: 85.5% [95% CI, 81.8-87.5%] vs 87.8% [95% CI, 84.1-90.7%], P = 0.339). However, abdominal discomfort and diarrhea were more common in the esomeprazole/sodium bicarbonate-treated group than in the tegoprazan-treated group (abdominal discomfort: 1.1% vs 3.8%, P = 0.012; diarrhea: 9.9% vs 21.2%, P < 0.001). DISCUSSION: The efficacy of the esomeprazole/sodium bicarbonate-based triple therapy for H. pylori eradication was comparable with that of the tegoprazan-based triple therapy. However, esomeprazole/sodium bicarbonate-based therapy exhibited a higher risk of abdominal discomfort and diarrhea than tegoprazan-based therapy.

The Risk of Venous Thromboembolism in Korean Patients with Breast Cancer: A Single-Center Experience.

The relationship between cancer and venous thromboembolism (VTE) has long been described. The risk of VTE in Asian patients with breast cancer remains largely unknown. This study described the incidence and risk factors of VTE in Korean patients with breast cancer. Data were collected from a retrospective database of patients who underwent breast cancer surgery between 2011 and 2020 at a single institution. The Cox proportional-hazards model was used to identify factors associated with VTE occurrences. Among the 2246 patients with breast cancer, 48 (2.1%) developed VTE during a median follow-up period of 53 months. The average incidence of VTE was 459 per 100,000 person-years. Age ≥ 60 years, male sex, chronic kidney disease, reconstructive procedures, and stage II or higher were independent predictive factors for VTE. VTE was associated with poor disease-free survival (hazard ratio (HR), 6.140; 95% confidence interval (CI), 3.480-10.835), and overall survival (HR, 8.842; 95% CI 4.386-17.824). Most VTE events were manageable with anticoagulation; three (6.3%) patients died of VTE, despite intensive care. The incidence of VTE was significantly elevated in Korean patients with breast cancer. Since VTE has a negative effect on oncologic outcomes of breast cancer, clinicians should manage its risk throughout their lifetime.

Production of a 135-residue long N-truncated human keratinocyte growth factor 1 in Escherichia coli.

BACKGROUND: Palifermin (trade name Kepivance®) is an amino-terminally truncated recombinant human keratinocyte growth factor 1 (KGF-1) with 140 residues that has been produced using Escherichia coli to prevent and treat oral mucositis following radiation or chemotherapy. In this study, an amino-terminally shortened KGF-1 variant with 135 residues was produced and purified in E. coli, and its cell proliferation activity was evaluated. RESULTS: We expressed soluble KGF-1 fused to thioredoxin (TRX) in the cytoplasmic fraction of E. coli to improve its production yield. However, three N-truncated forms (KGF-1 with 140, 138, and 135 residues) were observed after the removal of the TRX protein from the fusion form by cleavage of the human enterokinase light chain C112S (hEKL C112S). The shortest KGF-1 variant, with 135 residues, was expressed by fusion with TRX via the hEKL cleavage site in E. coli and purified at high purity (> 99%). Circular dichroism spectroscopy shows that purified KGF-1135 had a structure similar to that of the KGF-1140 as a random coiled form, and MCF-7 cell proliferation assays demonstrate its biological activity. CONCLUSIONS: We identified variations in N-terminus-truncated KGF-1 and selected the most stable form. Furthermore, by a simple two-step purification, highly purified KGF-1135 was obtained that showed biological activity. These results demonstrate that KGF-1135 may be considered an alternative protein to KGF-1.

Identification and Characterization of HEPN-MNT Type II TA System from Methanothermobacter thermautotrophicus ΔH.

Toxin-antitoxin (TA) systems are widespread in bacteria and archaea plasmids and genomes to regulate DNA replication, gene transcription, or protein translation. Higher eukaryotic and prokaryotic nucleotide-binding (HEPN) and minimal nucleotidyltransferase (MNT) domains are prevalent in prokaryotic genomes and constitute TA pairs. However, three gene pairs (MTH304/305, 408/409, and 463/464) of Methanothermobacter thermautotropicus ΔH HEPN-MNT family have not been studied as TA systems. Among these candidates, our study characterizes the MTH463/MTH464 TA system. MTH463 expression inhibited Escherichia coli growth, whereas MTH464 did not and blocked MTH463 instead. Using site-directed MTH463 mutagenesis, we determined that amino acids R99G, H104A, and Y106A from the R[ɸX]4-6H motif are involved with MTH463 cell toxicity. Furthermore, we established that purified MTH463 could degrade MS2 phage RNA, whereas purified MTH464 neutralized MTH463 activity in vitro. Our results indicate that the endonuclease toxin MTH463 (encoding a HEPN domain) and its cognate antitoxin MTH464 (encoding the MNT domain) may act as a type II TA system in M. thermautotropicus ΔH. This study provides initial and essential information studying TA system functions, primarily archaea HEPN-MNT family.

A ramus cortical bone harvesting technique without bone marrow invasion.

Autogenous bone grafts from the mandibular ramus are a known source of inadequate bone volume scenarios of the residual alveolar ridge. However, the conventional block-type harvesting technique cannot prevent bone marrow invasion, which can cause postoperative complications such as pain, swelling, and inferior alveolar nerve injury. This study aims to suggest a complication-free harvesting technique and present the results of bone grafting and donor sites. One patient received two dental implants with a complication-free harvesting technique that involves creation of ditching holes with a 1 mm round bur. Sagittal, coronal, and axial osteotomies produced grid-type cortical squares using a micro-saw and a round bur to confirm the cortical thickness. The grid-type cortical bone was harvested from the occlusal aspect, and the harvesting was extended through an additional osteotomy on the exposed and remaining cortical bone to prevent bone marrow invasion. The patient did not suffer postoperative severe pain, swelling, or numbness. After 15 months, the harvested site exhibited new cortical bone lining, and the grafted area had healed to a cortico-cancellous complex with functional loading of the implants. Our technique, grid-type cortical bone harvesting without bone marrow invasion, allowed application of autogenous bone without bone marrow invasion to achieve acceptable bone healing of the dental implants and to regenerate the harvested cortical bone.

Inoculation of ACC deaminase-producing endophytic bacteria down-regulates ethylene-induced pathogenesis-related signaling in red pepper (Capsicum annuum L.) under salt stress.

Pathogenesis-related (PR) signaling plays multiple roles in plant development under abiotic and biotic stress conditions and is regulated by a plethora of plant physiological as well as external factors. Here, our study was conducted to evaluate the role of an ACC deaminase-producing endophytic bacteria in regulating ethylene-induced PR signaling in red pepper plants under salt stress. We also evaluated the efficiency of the bacteria in down-regulating the PR signaling for efficient colonization and persistence in the plant endosphere. We used a characteristic endophyte, Methylobacterium oryzae CBMB20 and its ACC deaminase knockdown mutant (acdS- ). The wild-type M. oryzae CBMB20 was able to decrease ethylene emission by 23% compared to the noninoculated and acdS- M. oryzae CBMB20 inoculated plants under salt stress. The increase in ethylene emission resulted in enhanced hydrogen peroxide concentration, phenylalanine ammonia-lyase activity, ß-1,3 glucanase activity, and expression profiles of WRKY, CaPR1, and CaPTI1 genes that are typical salt stress and PR signaling factors. Furthermore, the inoculation of both the bacterial strains had shown induction of PR signaling under normal conditions during the initial inoculation period. However, wild-type M. oryzae CBMB20 was able to down-regulate the ethylene-induced PR signaling under salt stress and enhance plant growth and stress tolerance. Collectively, ACC deaminase-producing endophytic bacteria down-regulate the salt stress-mediated PR signaling in plants by regulating the stress ethylene emission levels and this suggests a new paradigm in efficient colonization and persistence of ACC deaminase-producing endophytic bacteria for better plant growth and productivity.

Polyhydroxybutyrate production from crude glycerol using a highly robust bacterial strain Halomonas sp. YLGW01.

Petrochemical-based plastics are hardly biodegradable and a major cause of environmental pollution, and polyhydroxybutyrate (PHB) is attracting attention as an alternative due to its similar properties. However, the cost of PHB production is high and is considered the greatest challenge for its industrialization. Here, crude glycerol was used as a carbon source for more efficient PHB production. Among the 18 strains investigated, Halomonas taeanenisis YLGW01 was selected for PHB production due to its salt tolerance and high glycerol consumption rate. Furthermore, this strain can produce poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(3HB-co-3 HV)) with 17 % 3 HV mol fraction when a precursor is added. PHB production was maximized through medium optimization and activated carbon treatment of crude glycerol, resulting in 10.5 g/L of PHB with 60 % PHB content in fed-batch fermentation. Physical properties of the produced PHB were analyzed, i.e., weight average molecular weight (6.8 × 105), number average molecular weight (4.4 × 105), and the polydispersity index (1.53). In the universal testing machine analysis, the extracted intracellular PHB showed a decrease in Young's modulus, an increase in Elongation at break, greater flexibility than authentic film, and decreased brittleness. This study confirmed that YLGW01 is a promising strain for industrial PHB production using crude glycerol.