An intra articular injectable Mitocelle recovers dysfunctional mitochondria in cellular organelle disorders.

Mitochondrial dysfunction increases ROS production and is closely related to many degenerative cellular organelle diseases. The NOX4-p22phox axis is a major contributor to ROS production and its dysregulation is expected to disrupt mitochondrial function. However, the field lacks a competitive inhibitor of the NOX4-p22phox interaction. Here, we created a povidone micelle-based Prussian blue nanozyme that we named "Mitocelle" to target the NOX4-p22phox axis, and characterized its impact on the major degenerative cellular organelle disease, osteoarthritis (OA). Mitocelle is composed of FDA-approved and biocompatible materials, has a regular spherical shape, and is approximately 88 nm in diameter. Mitocelle competitively inhibits the NOX4-p22phox interaction, and its uptake by chondrocytes can protect against mitochondrial malfunction. Upon intra-articular injection to an OA mouse model, Mitocelle shows long-term stability, effective uptake into the cartilage matrix, and the ability to attenuate joint degradation. Collectively, our findings suggest that Mitocelle, which functions as a competitive inhibitor of NOX4-p22phox, may be suitable for translational research as a therapeutic for OA and cellular organelle diseases related to dysfunctional mitochondria.

Smoking and serological response to influenza vaccine.

Cigarette smoking confers additional risk from influenza. This study assessed the effect of smoking on humoral immune response to influenza vaccine. Adults ≥50 y of age were enrolled during the 2011-2016 influenza vaccination seasons in an observational prospective study. Non-fasting whole blood samples for hemagglutination inhibition (HAI) assays were obtained from participants at pre- and 28 d post-clinically administered, trivalent influenza vaccination. Among 273 participants, 133 subjects self-reported as never smokers, 87 as ex-smokers, and 53 as current smokers. Postvaccination geometric mean HAI titers were significantly higher among smokers for A/H1N1 (p = .031) and A/H3N2 (p = .001). Relative to never smokers, smoking was independently related to seroconversion to A/H1N1, A/H3N2 and B. The adjusted odd ratios (ORs) were 5.2 [95% confidence interval (CI), 2.3, 11.5] for seroconversion to A/H1N1, 5.4 (95% CI, 2.4, 12.1) for A/H3N2, and 2.7 (95% CI, 1.3, 5.7) for B. Smoking was also independently related to seroprotection to A/H1N1, A/H3N2 and B. The ORs were 3.6 (95% CI, 1.6, 8.08) for seroprotection to A/H1N1 in smokers, 2.7 (95% CI, 1.14, 6.5) for A/H3N2, and 2.5 (95% CI, 1.1, 5.7) for B. Although the mechanism is unclear, smokers showed a better immune response to influenza vaccination than never smokers and ex-smokers. The results can be used to emphasize the value of influenza vaccination for smokers.

A prediction of mutations in infectious viruses using artificial intelligence.

Many subtypes of SARS-CoV-2 have emerged since its early stages, with mutations showing regional and racial differences. These mutations significantly affected the infectivity and severity of the virus. This study aimed to predict the mutations that occur during the evolution of SARS-CoV-2 and identify the key characteristics for making these predictions. We collected and organized data on the lineage, date, clade, and mutations of SARS-CoV-2 from publicly available databases and processed them to predict the mutations. In addition, we utilized various artificial intelligence models to predict newly emerging mutations and created various training sets based on clade information. Using only mutation information resulted in low performance of the learning models, whereas incorporating clade differentiation resulted in high performance in machine learning models, including XGBoost (accuracy: 0.999). However, mutations fixed in the receptor-binding motif (RBM) region of Omicron resulted in decreased predictive performance. Using these models, we predicted potential mutation positions for 24C, following the recently emerged 24A and 24B clades. We identified a mutation at position Q493 in the RBM region. Our study developed effective artificial intelligence models and characteristics for predicting new mutations in continuously evolving infectious viruses.

Real-world effectiveness of influenza vaccine over a decade during the 2011-2021 seasons-Implications of vaccine mismatch.

BACKGROUND: Influenza imposes a significant healthcare burden in Korea, leading the government to initiate a national immunization program. Previous studies on vaccine effectiveness (VE) were limited to single-season estimation in Korea. METHODS: This multicenter prospective cohort study enrolled patients with influenza-like illnesses at 10 medical centers in Korea from 2011 to 2021. The demographic and clinical data were collected from questionnaire surveys and electronic medical records. Using a test-negative design, we aimed to investigate the effectiveness of a seasonal influenza vaccine for antigenic matching of the vaccine and circulating viral strains over 10 seasons. RESULTS: Overall, 5322 adults aged ≥65 years were enrolled. Only three (33.3 %) of nine seasons showed >70 % antigenic match between vaccine and circulating strains. Influenza VE was significantly variable by season, ranging from -46.9 % (95 %confidence interval [CI]: -127.6-5.2) in the 2011/12 season to 47.7 % (95 %CI: 22.6-64.7) in the 2016/17 season. A significant difference was observed in the VE depending on whether the vaccine strains matched with epidemic strains: 28.8 % (95 %CI: 8.8-44.8) in matched seasons versus -12.0 % (95 %CI: -30.0-3.7) in mismatched seasons. Across the study period, influenza-related hospitalizations were reduced by 13.6 % (95 %CI: 0.7-24.8) with vaccination. In a subgroup analysis, the VE against influenza-related hospitalization was 48.4 % (95 %CI 29.6-62.2) in A/H3N2 dominant seasons and 53.8 % (95 %CI: -73.4-87.7) in A/H1N1 dominant seasons, respectively. CONCLUSION: Influenza vaccine mismatch was frequent over the study period, leading to negligibly low VE in mismatched seasons. Influenza vaccination reduces the risk of influenza-related hospitalizations.

Neoplastic progression risk in females with Barrett's esophagus: a systematic review and meta-analysis of individual patient data.

BACKGROUND AND AIMS: Females with Barrett's esophagus (BE) have a lower risk of neoplastic progression than males, but sufficiently powered risk analyses are lacking. This systematic review and meta-analysis of individual patient data (IPD) aims to provide more robust evidence on neoplastic progression risk in females. METHODS: Systematic literature search of three electronic databases (Medline, Embase, Google Scholar) from inception until August 2023. Eligible studies (1) reported original data on progression from non-dysplastic BE (NDBE), indefinite for dysplasia (IND) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), and (2) included female and male patients. IPD were quality controlled by two independent reviewers. Primary outcome was the association between sex and neoplastic progression risk, adjusted for risk factors using multivariable Cox regression analysis. Secondary outcomes were sex differences in time to progression and annual progression rate. RESULTS: IPD were obtained from 11/66 eligible studies, including 2.196 (31%) females. Neoplastic progression risk was lower in females (HR 1.44 for males vs females, 95%CI 1.13-1.82) after adjusting for age, smoking, medication use, hiatal hernia, BE length, and baseline pathology. Annual progression rate was 0.88% in females vs 1.29% in males. Time to progression was similar in both sexes; 3.7 years (IQR 2.1-7.7) in females, and 4.2 years (IQR 2.0-8.1) in males. CONCLUSION: Although females had a lower neoplastic progression risk, sex differences were smaller than previously reported and time to progression was similar for both sexes. Future research should focus on other factors than sex to identify low- and high-risk BE patients.

Effectiveness of the Bivalent mRNA COVID-19 Vaccine for Preventing Critical Infection From the SARS-CoV-2 Omicron Variant in the Republic of Korea.

BACKGROUND: This retrospective observational matched cohort study assessed the differences in critical infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the omicron-predominant period of the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the vaccine effectiveness of bivalent mRNA vaccine compared to unvaccinated individuals. METHODS: We collected COVID-19 case data from the Korean COVID-19 vaccine effectiveness cohort. We calculated the probability of critical COVID-19 cases by comparing the vaccinated and unvaccinated groups. RESULTS: The risk of being critically infected due to SAR-CoV-2 infection was 5.96 times higher (95% confidence interval, 5.63-6.38) among older individuals who were unvaccinated compared to those who received the bivalent COVID-19 vaccine. CONCLUSION: Our findings indicate that the bivalent vaccine reduces the disease burden of the SARS-CoV-2 omicron variant, particularly among the older population. Further studies are warranted to determine the effectiveness of booster doses of vaccines for SARS-CoV-2 infection.

Burden of Herpes Zoster in Individuals With Chronic Conditions in the Republic of Korea: A Nationwide Population-Based Database Study.

Background: Chronic conditions (CCs) may increase the risk of herpes zoster (HZ) infection, leading to a greater healthcare burden in these individuals compared to those without CCs. It is therefore clinically important to quantify HZ disease burden in individuals with and without CCs, given the rapidly aging population in the Republic of Korea (ROK). Methods: This retrospective cohort study examines the trends in incidence rates (IRs) and incidence rate ratios (IRRs) in individuals aged ≥18 years with CCs, using the National Health Insurance Service National Sample Cohort (NHIS-NSC) database from 2010 to 2019. These patients were stratified by age group, sex, HZ complications, and CCs. The annual average number of HZ patients, IRs, and IRRs were calculated for individuals with and without CCs. Results: In total, 729 347 patients with HZ were eligible for the study. HZ IRs were highest in patients with diabetes, followed by chronic obstructive pulmonary disease, chronic kidney disease, asthma, and chronic liver disease, with HZ IRRs following a similar trend. Overall, HZ IRs generally increased with age, typically peaking at 60-64 or 65-69 years, and were similar for females and males. HZ IRs were highest among patients without complications, followed by HZ with other, cutaneous, ocular, and neurologic complications across all CCs. For each of the CCs, HZ IRs were consistently higher than those of the non-CC population regardless of sex. Conclusions: The findings of this study reiterate the importance of HZ prevention for healthy aging, especially for CC populations at increased risk of HZ in the ROK.

Highly Water-Dispersed Natural Fullerenes Coated with Pluronic Polymers as Novel Nanoantioxidants for Enhanced Antioxidant Activity.

Fullerene is a cosmic material with a buckyball-like structure comprising 60 carbon atoms. It has attracted significant interest because of its outstanding antioxidant, antiviral, and antibacterial properties. Natural fullerene (NC60) in shungite meets the demand of biomedical fields to scavenge reactive oxygen species in many diseases. However, its hydrophobicity and poor solubility in water hinder its use as an antioxidant. In this study, highly water-dispersed and stable Pluronic-coated natural fullerene nanoaggregates (NC60/Plu) were prepared from various Pluronic polymers. The water dispersity and stability of NC60 were compared and optimized based on the characteristics of Pluronic polymers including F68, F127, L35, P123, and L81. In particular, NC60 coated with Pluronic F127 at a weight ratio of 1 to 5 showed excellent antioxidant effects both in situ and in vitro. This suggests that the high solubilization of NC60 in Pluronic polymers increases its chance of interacting with reactive oxygen radicals and improves radical scavenging activity. Thus, the optimized NC60/PF127 may be a novel biocompatible antioxidant for treating various diseases associated with oxidative stress.

Prediction Equations for Calculating Maximal Inspiratory Pressure from Spirometry and Thoracic Ultrasound After COVID-19 with Gastroesophageal Reflux Disease in Indonesian Adults: A Cross-sectional Study.

BACKGROUND: This study aimed to determine the prediction equations for calculating maximal inspiratory pressure using spirometry and thoracic ultrasonography (USG) after COVID-19 with gastroesophageal reflux disease (GERD).  Methods: This cross-sectional study was conducted from January to December 2022 and included Indonesian adults recruited by consecutive sampling after they developed COVID-19 with GERD symptoms. The following tests were used: spirometry (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1); thoracic USG (left diaphragm excursion (LDE) and right diaphragm excursion (RDE); and respirometry (maximal inspiratory pressure (MIP). The data were analyzed using Pearson correlational analysis and multiple linear regression. RESULTS: Sixty-two participants were recruited: mean age 37.23 ± 9.76 years and average MIP 49.85 ± 18.13 cmH2O. MIP correlated significantly with FVC (r = 0.307; p = 0.015), LDE (r = 0.249; p = 0.051), FEV1(r = 0.186; p = 0.147), and RDE (r = 0.156; p = 0.221). We developed two models based on their applicability. Model 1 provides an MIP prediction equation for health facilities that have only spirometry: 23.841 - (20.455 × FEV1) + (26.190 × FVC). Model 2 provides an MIP prediction equation for health facilities that have both spirometry and thoracic USG: 3.530 - (20.025 × FEV1) + (25.354 × FVC) + (4.819 × LDE). CONCLUSION: In this study, measures of respiratory function correlated significantly with diaphragm excursion. MIP can be predicted from spirometry and thoracic USG data. Healthcare facilities can choose the prediction equation model that best meets their situation.

Immediate Effects of Two Different Methods of Trunk Elastic Taping on Pelvic Inclination, Trunk Impairment, Balance, and Gait in Stroke Patients.

Background and Objectives: Stroke patients often experience changes in their pelvic tilt, trunk impairments and decreased gait and balance. While various therapeutic interventions have been attempted to improve these symptoms, there is a need for interventions that are easy to apply and reduce the physical labor of physical and occupational therapists. We aimed to investigate the immediate effects of two different methods of trunk elastic taping on the pelvic inclination, trunk impairment, balance, and gait in chronic stroke patients. Materials and Methods: We performed a single-blind randomized controlled trial involving 45 patients with chronic stroke. Participants were randomly assigned to one of three groups: forward rotation with posterior pelvic tilt taping (FRPPT, n = 14), backward rotation with posterior pelvic tilt taping (BRPPT, n = 14), or placebo taping (PT = 14). This study was conducted from December 2023 to January 2024. All the measurements were performed twice: before the intervention and immediately after the intervention. The pelvic inclination was assessed using the anterior pelvic tilt angle. The trunk impairment scale (TIS) was used to measure the trunk impairment. The balance and gait were evaluated using a force plate and walkway system. Results: The pelvic inclination was significantly different in the FRPPT and BRPPT groups compared to the PT group (p < 0.05, p < 0.001). The TIS and gait were significantly increased in the FRPPT group compared to the PT group (p < 0.05). The balance significantly improved in the FRPPT and BRPPT within groups (p < 0.05). Conclusions: Two different methods of posterior pelvic tilt taping improved the anterior pelvic tilt in chronic hemiplegic stroke patients compared with PT, and the FRPPT method also improved the trunk impairment and gait. Therefore, posterior pelvic tilt taping can be used as an intervention with immediate effect.

Cystic Angiomyofibroblastoma of the Uterus Mimicking Ovarian Cancer.

Angiomyofibroblastoma (AMFB) is an exceedingly rare mesenchymal tumor of the lower genital tract. AMFB primarily affects the pelviperineal region, especially the vulvar in premenopausal women. Typically, AMFB is a benign disease and does not have the potential for metastasis or recurrence, requiring complete surgical excision. Its accurate differentiation from aggressive angiomyxoma is critical due to varying prognoses. A 51-year-old woman, diagnosed with mucinous carcinoma of the breast, presented with a 12 cm abdominopelvic mass identified during breast cancer staging. Imaging suggested an ovarian origin; however, surgical exploration revealed a stalk-attached cystic mass in the anterior body of the uterus. Histopathology confirmed AMFB. Immunohistochemical analysis showed positivity for estrogen and progesterone receptors and smooth muscle actin. The patient continued breast cancer treatment postoperatively without pelvic mass recurrence or complications for a postoperative follow-up period of one year. This case highlights AMFB's potential uterine body origin, expending known tumor sites and complicating diagnosis due to overlapping features with other mesenchymal tumors. Accurate diagnosis using immunohistochemical markers and pathological features is essential to avoid unnecessary aggressive treatments. The uterine location in this case suggests a possible shared pathogenesis with uterine myomas, warranting further research into their connection. Reporting the first case of AMFB originating in the uterine body enhances understanding of this rare condition and underscores the importance of clinical awareness and precise diagnostic strategies to guide management and improve outcomes.

Furthering decent work by expanding the role of occupational safety and health.

BACKGROUND: The International Labour Organization (ILO) and the United Nations (UN) have promoted the concept of decent work as a Sustainable Development Goal for 2030 to address critical global problems. Occupational safety and health (OSH) are components of decent work, primarily through the ILO social protection objective of the goal, and are linked to various other objectives. OBJECTIVE: This Commentary applies a previously published staging framework to stimulate thinking about how the OSH field can contribute further to the achievement of decent work. METHODS: To advance the contribution of the framework, the different functions of OSH (research, practice, advocacy, governance, and professional education) were used to identify impediments to achieving decent work and develop recommendations for each determinant in the framework. RESULTS: Promoting and achieving decent work are complex issues that require a multifactorial approach. Numerous recommendations supporting systems thinking and transdisciplinary approaches are provided. CONCLUSIONS: The OSH field can expand to further address decent work.

Phytochemical-Based Nanoantioxidants Stabilized with Polyvinylpyrrolidone for Enhanced Antibacterial, Antioxidant, and Anti-Inflammatory Activities.

Despite the inhibitory effect of phytoncide (Pht) on food-borne pathogenic bacterial growth, the hydrophobic nature and susceptibility to biodegradation under physiological conditions limits its applications. Here, we developed Pht-loaded polyvinylpyrrolidone (PVP) micelles (Pht@PVP MC) via micelle packing. Pht was solubilized using different types of PVP as micellar vehicles. The as-prepared Pht@PVP MCs were characterized using dynamic light scattering and transmission electron microscopy. The sizes of the Pht@PVP MCs were controlled from 301 ± 51 to 80 ± 3 nm by adjusting the PVP content. The polydispersity index of Pht@PVP MC was between 0.21 ± 0.03 and 0.16 ± 0.04, indicating homogeneous size. A colony-counting method was employed to evaluate the improvement in antibacterial activity after Pht encapsulation in PVP micelles. The reactive oxygen species (ROS)-scavenging activity and anti-inflammatory efficacy of Pht@PVP MC were analyzed in a concentration range of 10-100 µg/mL by evaluating in vitro ROS and nitric oxide levels using DCFDA and Griess reagents. PVP with both hydrophobic and hydrophilic moieties improved the aqueous solubility of Pht and stabilized it via steric hindrance. Higher-molecular-weight PVP at higher concentrations resulted in a smaller hydrodynamic diameter of Pht@PVP MC with uniform size distribution. The spherical Pht@PVP MC maintained its size and polydispersity index in a biological buffer for 2 weeks. Pht@PVP MC exhibited enhanced antibacterial activity compared to bare Pht. The growth of Staphylococcus aureus was effectively inhibited by Pht@PVP MC treatment. Furthermore, biocompatible Pht@PVP MC exhibited dose-dependent antioxidant and anti-inflammatory activities in vitro. Overall, Pht@PVP MC is an effective alternative to synthetic antibacterial, antioxidant, and anti-inflammatory chemicals.

Functional pathogenicity of ESRRB variant of uncertain significance contributes to hearing loss (DFNB35).

Advances in next-generation sequencing technologies have led to elucidation of sensorineural hearing loss genetics and associated clinical impacts. However, studies on the functional pathogenicity of variants of uncertain significance (VUS), despite their close association with clinical phenotypes, are lacking. Here we identified compound heterozygous variants in ESRRB transcription factor gene linked to DFNB35, specifically a novel splicing variant (NM_004452.4(ESRRB): c.397 + 2T>G) in trans with a missense variant (NM_004452.4(ESRRB): c.1144C>T p.(Arg382Cys)) whose pathogenicity remains unclear. The splicing variant (c.397 + 2T>G) caused exon 4 skipping, leading to premature stop codon formation and nonsense-mediated decay. The p.(Arg382Cys) variant was classified as a VUS due to its particularly higher allele frequency among East Asian population despite disease-causing in-silico predictions. However, functional assays showed that p.(Arg382Cys) variant disrupted key intramolecular interactions, leading to protein instability. This variant also reduced transcriptional activity and altered expression of downstream target genes essential for inner ear function, suggesting genetic contribution to disease phenotype. This study expanded the phenotypic and genotypic spectrum of ESRRB in DFNB35 and revealed molecular mechanisms underlying ESRRB-associated DFNB35. These findings suggest that variants with high allele frequencies can also possess functional pathogenicity, providing a breakthrough for cases where VUS, previously unexplored, could be reinterpreted by elucidating their functional roles and disease-causing characteristics.

Viral Load-Based Prediction of Hepatocellular Carcinoma Risk in Noncirrhotic Patients With Chronic Hepatitis B : A Multinational Study for the Development and External Validation of a New Prognostic Model.

BACKGROUND: A nonlinear association between serum hepatitis B virus (HBV) DNA levels and hepatocellular carcinoma (HCC) risk has been suggested in patients with chronic hepatitis B (CHB). OBJECTIVE: To develop and externally validate a prognostic model for HCC risk in noncirrhotic adult patients with CHB and no notable alanine aminotransferase (ALT) elevation. DESIGN: Multinational cohort study. SETTING: A community-based cohort in Taiwan (REVEAL-HBV [Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus]; REACH-B [Risk Estimation for HCC in CHB] model cohort) and 8 hospital-based cohorts from Korea and Hong Kong (GAG-HCC [Guide with Age, Gender, HBV DNA-HCC] and CU-HCC [Chinese University-HCC] cohorts). PARTICIPANTS: Model development: 6949 patients with CHB from a Korean hospital-based cohort. External validation: 7429 patients with CHB combined from the Taiwanese cohort and 7 cohorts from Korea and Hong Kong. MEASUREMENTS: Incidence of HCC. RESULTS: Over median follow-up periods of 10.0 and 12.2 years, the derivation and validation cohorts identified 435 and 467 incident HCC cases, respectively. Baseline HBV DNA level was one of the strongest predictors of HCC development, demonstrating a nonlinear parabolic association in both cohorts, with moderate viral loads (around 6 log10 IU/mL) showing the highest HCC risk. Additional predictors included in the new model (Revised REACH-B) were age, sex, platelet count, ALT levels, and positive hepatitis B e antigen result. The model exhibited satisfactory discrimination and calibration, with c-statistics of 0.844 and 0.813 in the derivation and validation cohorts with multiple imputation, respectively. The model yielded a greater positive net benefit compared with other strategies in the 0% to 18% threshold. LIMITATION: Validation in cohorts of other races and receiving antiviral treatment was lacking. CONCLUSION: Our new prognostic model, based on the nonlinear association between HBV viral loads and HCC risk, provides a valuable tool for predicting and stratifying HCC risk in noncirrhotic patients with CHB who are not currently indicated for antiviral treatment. PRIMARY FUNDING SOURCE: Korean government.

Discovery, Characterization, and Structure of a Cell Active PAD2 Inhibitor Acting through a Novel Allosteric Mechanism.

Peptidyl arginine deiminases (PADs) are important enzymes in many diseases, especially those involving inflammation and autoimmunity. Despite many years of effort, developing isoform-specific inhibitors has been a challenge. We describe herein the discovery of a potent, noncovalent PAD2 inhibitor, with selectivity over PAD3 and PAD4, from a DNA-encoded library. The biochemical and biophysical characterization of this inhibitor and two noninhibitory binders indicated a novel, Ca2+ competitive mechanism of inhibition. This was confirmed via X-ray crystallographic analysis. Finally, we demonstrate that this inhibitor selectively inhibits PAD2 in a cellular context.

Biocompatibility and dimensional stability through the use of 3D-printed scaffolds made by polycaprolactone and bioglass-7: An in vitro and in vivo study.

PURPOSE: This experiment aimed to observe the differences in biological properties by producing BGS-7 + PCL scaffolds with different weight fractions of BGS-7 through 3D printing and to confirm whether using the scaffold for vertical bone augmentation is effective. MATERIALS AND METHODS: Cube-shaped bioglass (BGS-7) and polycaprolactone (PCL) scaffolds with different weight fractions (PCL alone, PCL with 15% and 30% BGS-7) are produced using 3D printing. The surface hydroxyapatite (HA) apposition, the pH change, proliferation and attachment assays, and various gene expression levels are assessed. After a 7-mm implant was inserted 3 mm into the rabbit calvaria, vertical bone augmentation is performed around the implant and inside the scaffold in four ways: scaffold only, scaffold+bone graft, bone graft only, and no graft. Sacrifice is performed at 6, 12, and 24 weeks, and the various parameters are compared radiographically and histologically. RESULTS: HA apposition, cell proliferation, cell attachment, and expression of osteogenic genes increase as the proportion of BGS-7 increase. In the in vivo test, a higher bone-implant contact ratio, bone volume ratio, bone mineral density, and new bone area are observed when the scaffold and bone grafts were used together. CONCLUSION: The 3D-printed scaffold, a mixture of BGS-7 and PCL, exhibit higher biological compatibility as the proportion of BGS-7 increase. Additionally, the use of scaffold is effective for vertical bone augmentation.

Chemical induction of the interaction between AIMP2-DX2 and Siah1 to enhance ubiquitination.

AIMP2-DX2 (hereafter DX2) is an oncogenic variant of aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) that mediates tumorigenic interactions with various factors involved in cancer. Reducing the levels of DX2 can effectively inhibit tumorigenesis. We previously reported that DX2 can be degraded through Siah1-mediated ubiquitination. In this study, we identified a compound, SDL01, which enhanced the interaction between DX2 and Siah1, thereby facilitating the ubiquitin-dependent degradation of DX2. SDL01 was found to bind to the pocket surrounding the N-terminal flexible region and GST domain of DX2, causing a conformational change that stabilized its interaction with Siah1. Our findings demonstrate that protein-protein interactions (PPIs) can be modulated through chemically induced conformational changes.

The effect of nebulized N-acetylcysteine on the phlegm of chronic obstructive pulmonary disease: the NEWEST study.

BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.