Suppressing anti-citrullinated protein antibody-induced osteoclastogenesis in rheumatoid arthritis using anti-CD64 and PAD-2 inhibitors.

OBJECTIVES: To evaluate the role of Fcγ receptors (FcγR) and peptidyl arginine deiminase (PAD) in anti-citrullinated protein antibody (ACPA)-induced fibroblast-like synoviocytes (FLSs)-mediated osteoclastogenesis in patients with rheumatoid arthritis (RA). METHODS: FLSs and peripheral blood mononuclear cells were collected from patients with RA. We stimulated RA-FLS with ACPA (100 ng/ml) with and without anti-cluster of differentiation (CD)32a/CD64 (FcγRIIA/FcγRI) antibody and PAD-2/4 inhibitors. Flow cytometry and enzyme-linked immunosorbent assay were also performed. CD14+ monocytes were cultured with receptor activator of nuclear factor kappa beta (RANKL) and macrophage colony-stimulating factor, and ACPA-stimulated RA-FLSs were added. These cells were cultured for 14 days, and osteoclastogenesis was quantified using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: ACPA increased RANKL+ and tumour necrotic factor-alpha (TNF-α+) FLS, which decreased dose-dependently by adding 5 and 10 ug/mL anti-CD64 antibody rather than anti-CD32a antibody. In PAD inhibitor experiments, the proportion of RANKL+ and TNF-α+ FLS decreased in 50 µM condition containing PAD-2 inhibitor rather than PAD-4 inhibitor. The co-culture of ACPA-stimulated RA-FLSs and osteoclast precursors increased the TRAP+ multinucleated osteoclast count, which was decreased by anti-CD64 antibody and PAD2 inhibitor. CONCLUSIONS: The present study showed that ACPA increased RANKL and pro-inflammatory cytokine expression in RA-FLSs, and ACPA-activated RA-FLSs could augment osteoclastogenesis. These processes were inhibited by treatment with anti-CD64 antibody and PAD-2 inhibitors. These results show that CD64 and PAD-2-induced pathways may be involved in ACPA-induced FLS activation and osteoclastogenesis in patients with RA. Therefore, regulating the CD64 and PAD-2 pathways may improve RA treatment.

Effectiveness and safety of East Asian herbal medicine for menopausal insomnia: a systematic review and meta-analysis.

Background: Menopausal insomnia significantly impacts the quality of life in women. East Asian herbal medicines (EAHMs) have been traditionally used in Asian countries, but their efficacy and safety require systematic evaluation. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of EAHM for treating menopausal insomnia. Methods: A comprehensive literature search was conducted across 10 electronic databases from inception until 19 July 2023. Randomized controlled trials (RCTs) investigating EAHM for menopausal insomnia were included. Two reviewers independently screened studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. The primary outcome was sleep quality, insomnia severity, and sleep architecture. Secondary outcomes included total effective rate (TER), menopausal symptoms, and adverse effects. Meta-analysis was conducted using a random-effects model, and the results were calculated as mean differences (MDs) or risk ratios (RRs) and their 95% confidence intervals (CIs). Also, the certainty of evidence was assessed using the GRADE approach. Results: A total of 70 RCTs involving 6,035 participants met the inclusion criteria. The most frequently used EAHMs were modified Suan Zao Ren Tang, and the most frequently used herbal component was Zizyphus jujuba Miller var. spinosa Hu ex H. F. Chou [Rhamnaceae; Zizyphi Semen]. Compared with sedative-hypnotics, EAHM significantly improved sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI) (MD -2.18, 95% CI -2.56 to -1.80), and reduced menopausal symptoms, as assessed by the Kupperman Index (MD -4.92, 95% CI -6.03 to -3.80). Similar results were seen when EAHM was added to sedative-hypnotics. When EAHM was additionally used in sedative-hypnotics, similar benefits were shown for PSQI (MD -2.46, 95% CI -3.09 to -1.82) and the Kupperman Index (MD -4.64, 95% CI -5.07 to -4.21). EAHM was generally safer than sedative-hypnotics, with significantly fewer adverse reactions (RR 0.15, 95% CI 0.07-0.34). However, the certainty of evidence was moderate to low. Conclusion: EAHMs, alone or with sedative-hypnotics, may be effective and safe for improving sleep quality and managing menopausal symptoms. Future studies should include diverse populations, rigorous methodologies, and explore mechanisms of action to confirm these findings. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?], identifier [CRD42023446708].

Symptom-specific non-pharmacological interventions for behavioral and psychological symptoms of dementia: An umbrella review.

BACKGROUND: Non-pharmacological interventions are considered the first-line treatment for managing the behavioral and psychological symptoms of dementia. Given the heterogeneous characteristics of these symptoms, which vary for each individual and tend to fluctuate, a symptom-specific approach is necessary for providing individualized non-pharmacological interventions for people with dementia. However, clear guidelines regarding the appropriate types of interventions for individual symptoms or clusters of behavioral and psychological symptoms of dementia are lacking. OBJECTIVES: The aim of this umbrella review was to summarize the current evidence on non-pharmacological interventions for behavioral and psychological symptoms of dementia and provide guidance for determining the appropriate types of interventions for each behavioral and psychological symptom of dementia. DESIGN: An umbrella review of systematic reviews and/or meta-analyses. METHODS: The Cochrane methodology for umbrella reviews was employed for this review, and the review protocol was registered. PubMed, CINAHL, Embase, PsycINFO, and Cochrane databases were searched for relevant reviews using the 'population, intervention, control, and outcomes' formulation. Two reviewers independently screened the extracted articles for eligibility. The quality of each selected review was independently assessed by the two reviewers using A Measurement Tool to Assess Systematic Reviews 2. The results were narratively synthesized and categorized according to each symptom. RESULTS: Thirty-five systematic reviews, 71 % of which were also meta-analyses, were included in this review. The methodologies employed in the included reviews were significantly heterogeneous. The qualities of the reviews ranged from low to moderate. Diverse types of non-pharmacological interventions were identified in the reviews, with music therapy being the most frequently discussed. Among the various symptoms, depression was most frequently addressed, followed by overall symptoms, agitation, anxiety, sleep problems, and apathy. Music therapy was found to be effective for improving both overall and specific symptoms, including depression and anxiety. Notably, relatively weak evidence supports the effectiveness of exercise in addressing each symptom. Aromatherapy could be considered for agitation, whereas reminiscence may be effective in managing overall and specific symptoms, such as depression. CONCLUSIONS: The results showed that the evidence of symptom-specific effectiveness of non-pharmacological interventions varied across the different behavioral and psychological symptoms of dementia, highlighting the need for a symptom-specific approach in future research. Furthermore, future research is needed to facilitate the development of symptom-specific guidelines that can enhance the quality of individualized dementia care. REGISTRATION: Registered with PROSPERO (number: CRD42022340930) on November 9, 2022.

Dual role of transient receptor potential ankyrin 1 in respiratory and gastrointestinal physiology: From molecular mechanisms to therapeutic targets.

The transient receptor potential ankyrin 1 (TRPA1) channel plays a pivotal role in the respiratory and gastrointestinal tracts. Within the respiratory system, TRPA1 exhibits diverse distribution patterns across key cell types, including epithelial cells, sensory nerves, and immune cells. Its activation serves as a frontline sensor for inhaled irritants, triggering immediate protective responses, and influencing airway integrity. Furthermore, TRPA1 has been implicated in airway tissue injury, inflammation, and the transition of fibroblasts, thereby posing challenges in conditions, such as severe asthma and fibrosis. In sensory nerves, TRPA1 contributes to nociception, the cough reflex, and bronchoconstriction, highlighting its role in both immediate defense mechanisms and long-term respiratory reflex arcs. In immune cells, TRPA1 may modulate the release of pro-inflammatory mediators, shaping the overall inflammatory landscape. In the gastrointestinal tract, the dynamic expression of TRPA1 in enteric neurons, epithelial cells, and immune cells underscores its multifaceted involvement. It plays a crucial role in gut motility, visceral pain perception, and mucosal defense mechanisms. Dysregulation of TRPA1 in both tracts is associated with various disorders such as asthma, Chronic Obstructive Pulmonary Disease, Irritable Bowel Syndrome, and Inflammatory Bowel Disease. This review emphasizes the potential of TRPA1 as a therapeutic target and discusses the efficacy of TRPA1 antagonists in preclinical studies and their promise for addressing respiratory and gastrointestinal conditions. Understanding the intricate interactions and cross-talk of TRPA1 across different cell types provides insight into its versatile role in maintaining homeostasis in vital physiological systems, offering a foundation for targeted therapeutic interventions.

Comparative analysis of obstetric, perinatal, and neurodevelopmental outcomes following chorionic villus sampling and amniocentesis.

Background: The risks of invasive prenatal tests are reported in previous studies such as miscarriage, fetal anomalies, and bleeding. However, few compare short-term and long-term outcomes between invasive tests. This study aims to investigate obstetric, perinatal, and children's neurodevelopmental outcomes following chorionic villus sampling (CVS) or amniocentesis in singleton pregnancy. Methods: This retrospective cohort study included healthy singleton pregnancies underwent transabdominal CVS (gestational age [GA] at 10-13 weeks) or amniocentesis (GA at 15-21 weeks) at a single medical center between 2012 and 2022. Only cases with normal genetic results were eligible. Short-term and long-term neurodevelopmental outcomes were evaluated. Results: The study included 200 CVS cases and 498 amniocentesis cases. No significant differences were found in body mass index, parities, previous preterm birth, conception method, and cervical length (CL) before an invasive test between the groups. Rates of preterm labor, preterm premature rupture of the membranes, preterm birth, neonatal survival, neonatal short-term morbidities, and long-term neurodevelopmental delay were similar. However, the CVS group had a higher rate of cervical cerclage due to short CL before 24 weeks (7.0%) compared to the amniocentesis group (2.4%). CVS markedly increased the risk of cervical cerclage due to short CL (adjusted odd ratio [aOR] = 3.17, 95%CI [1.23-8.12], p = 0.016), after considering maternal characteristics. Conclusion: Performing CVS resulted in a higher incidence of cerclage due to short cervix or cervical dilatation compared to amniocentesis in singleton pregnancies. This highlights the importance of cautious selection for CVS and the necessity of informing women about the associated risks beforehand.

Protective Effects of Changbudodam-tang on Cell Death Signals on the Bone Marrow-Derived Human Mesenchymal Stem Cells via Regulation of MKK7/JNK/c-Jun Signaling Pathway.

Objectives: Polycystic ovary syndrome (PCOS) is one of the most common disorders and it shows up to 20% prevalence in reproductive-aged women populations, but no cures are available to date. We aimed to investigate the protective effects of Changbudodam-tang (CBD) on cell death signaling pathways, inflammation, and oxidative stress observed in Bone-Marrow derived human mesenchymal stem cell (BM-hMSC) by means of PCOS therapeutics in the future. Methods: BM-hMSCs were applied with cell deaths and injuries. Apoptosis and pyroptosis signals were quenched with their related signaling pathways using quantitative PCR, Western blot, and fluorescence image analysis. Results: Our data clearly displayed hydrogen peroxide- and nigericin-treated cell death signaling pathways via regulations of mitochondrial integrity and interleukin (IL)-1ß at the cellular levels (p < 0.01 or 0.001). We further observed that pre-treatment with CBD showed protective effects against oxidative stress by enhancement of antioxidant components at the cellular level, with respect to both protein and mRNA expression levels (p < 0.05, 0.01 or 0.001). The mechanisms of CBD were examined by Western blot analysis, and it showed anti-cell death, anti-inflammatory, and antioxidant effects via normalizations of the Jun N-terminal kinase/mitogen-activated protein kinase kinase 7/c-Jun signaling pathways. Conclusion: This study confirmed the pharmacological properties of CBD by regulation of cellular oxidation and the inflammation-provoked cell death condition of BM-hMSCs, which is mediated by the MKK7/JNK/c-Jun signaling pathway.

Interleukin-18 binding protein regulates mast cell activation and mast cell induced osteoclastogenesis of rheumatoid arthritis.

OBJECTIVES: Mast cell activation induces pathological responses, including increased osteoclastogenesis in rheumatoid arthritis (RA). Interleukin (IL)-18 binding protein (IL-18BP) has anti-inflammatory effects. In this study, we evaluated the effect of IL-18BP on mast cell activation and mast cell induced osteoclastogenesis. METHODS: Mast cells were activated by IL-33 (100 ng/mL) and cultured with IL-18BP (10, 50, and 100 ng/mL). The proliferation, apoptosis, and necroptosis of mast cells were measured using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of mast cell enzymes, matrix metalloproteinase (MMP), soluble RANKL (sRANKL), and pro-inflammatory cytokines in the culture media. Monocytes from patients with RA patients (n=5) were cultured with activated mast cells with various concentrations of IL-18BP. TRAP+ multinucleated osteoclasts, bone resorption area, and osteoclast differentiation-related genes were measured. RESULTS: Proliferation of tryptase+chymase+c-kit+FcεR1+ mast cells was suppressed following incubation with IL-18BP (10, 50, and 100 ng/mL). RNA expression levels of tryptase and chymase were reduced by 100 ng/mL IL-18BP. Additionally, the levels of MMP-3/9, IL-17A, IL-6, TNF-α, and sRANKL were significantly inhibited by 100 ng/mL IL-18BP. Annexin V+ and annexin V-PI+ mast cells were reduced following incubation with 100 ng/mL IL-18BP. The addition of IL-33 significantly stimulated mast cell and increased TRAP+ multinucleated cells and bone resorption area, and these effects were suppressed by IL-18BP. The osteoclast-related genes (TRAP, ATP6v0d2, RANK, and cathepsin K) expression were suppressed by IL-18BP. CONCLUSIONS: IL-18BP suppressed mast cell activation and mast cell induced osteoclastogenesis. This suggests a potential anti-arthritic role for IL-18BP in patients with RA.

The relationship between caregivers' behaviors and resistant behaviors of persons living with dementia during personal care in long-term care facilities: A lag sequential analysis.

Many older adults living with dementia exhibit resistant behaviors. Person-centered care is the gold standard of care; however, the sequential relationship between resistant and caregiving behaviors has not been identified. This study examined the sequential relationship between caregiving and care-resistant behaviors and analyzed 68 videos of personal care encounters of 21 residents living in four long-term care facilities. The videos were coded focusing on two sequences of behavior: residents' resistant behaviors and caregivers' behaviors. Lag sequential analysis was conducted using initial-response behavior pairs (resident-caregiver behavior or caregiver-resident behavior pairs). Person-centered care led to less resistant behavior (odds ratio 0.23; 95 % confidence interval 0.16, 0.33), whereas less person-centered care was followed by resistant behaviors (odds ratio 0.42; 95 % confidence interval 0.30, 0.59). A significant sequential association was found between task-centered behavior and resistant behavior. Hence, rigorous efforts are recommended to provide person-centered care through multilevel efforts.

Microbial production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate), from lab to the shelf: A review.

Polyhydroxyalkanoates (PHAs) are natural biopolyesters produced by microorganisms that represent one of the most promising candidates for the replacement of conventional plastics due to their complete biodegradability and advantageous material properties which can be modulated by varying their monomer composition. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] has received particular research attention because it can be synthesized based on the same microbial platform developed for poly(3-hydroxybutyrate) [P(3HB)] without much modification, with as high productivity as P(3HB). It also offers more useful mechanical and thermal properties than P(3HB), which broaden its application as a biocompatible and biodegradable polyester. However, a significant commercial disadvantage of P(3HB-co-3HV) is its rather high production cost, thus many studies have investigated the economical synthesis of P(3HB-co-3HV) from structurally related and unrelated carbon sources in both wild-type and recombinant microbial strains. A large number of metabolic engineering strategies have also been proposed to tune the monomer composition of P(3HB-co-3HV) and thus its material properties. In this review, recent metabolic engineering strategies designed for enhanced production of P(3HB-co-3HV) are discussed, along with their current status, limitations, and future perspectives.

Artificial intelligence-based radiographic extent analysis to predict tuberculosis treatment outcomes: a multicenter cohort study.

Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture conversion, focusing on artificial intelligence (AI)-based chest X-ray analysis and Xpert MTB/RIF assay cycle threshold (Ct) values. In this retrospective study across six South Korean referral centers (January 1 to December 31, 2019), we included adults with rifampicin-susceptible pulmonary tuberculosis confirmed by Xpert assay from sputum samples. We analyzed patient characteristics, AI-based tuberculosis extent scores from chest X-rays, and Xpert Ct values. Of 230 patients, 206 (89.6%) achieved treatment success. The median age was 61 years, predominantly male (76.1%). AI-based radiographic tuberculosis extent scores (median 7.5) significantly correlated with treatment success (odds ratio [OR] 0.938, 95% confidence interval [CI] 0.895-0.983) and culture conversion at 8 weeks (liquid medium: OR 0.911, 95% CI 0.853-0.973; solid medium: OR 0.910, 95% CI 0.850-0.973). Sputum smear positivity was 49.6%, with a median Ct of 26.2. However, Ct values did not significantly correlate with major treatment outcomes. AI-based radiographic scoring at diagnosis is a significant predictor of treatment success and culture conversion in pulmonary tuberculosis, underscoring its potential in personalized patient management.

GLP-1 and Its Derived Peptides Mediate Pain Relief Through Direct TRPV1 Inhibition Without Affecting Thermoregulation.

Hormonal regulation during food ingestion and its association with pain prompted the investigation of the impact of glucagon-like peptide-1 (GLP-1) on the transient receptor potential vanilloid 1 (TRPV1). Both endogenous and synthetic GLP-1 and an antagonist of GLP-1, exendin 9-39, reduced heat sensitivity in naïve mice. GLP-1-derived peptides (liraglutide, exendin-4, and exendin 9-39) effectively inhibited capsaicin (CAP)-induced currents and calcium responses in cultured sensory neurons and TRPV1-expressing cell lines. Notably, the exendin 9-39 alleviated CAP-induced acute pain, as well as chronic pain induced by complete Freund's adjuvant (CFA) and spared nerve injury (SNI) in mice, without causing hyperthermia associated with other TRPV1 inhibitors. Electrophysiological analyses revealed that exendin 9-39 binds to the extracellular side of TRPV1, functioning as a noncompetitive inhibitor of CAP. Exendin 9-39 did not affect proton-induced TRPV1 activation, suggesting its selective antagonism. Among exendin 9-39 fragments, exendin 20-29 specifically binds to TRPV1, alleviating pain in both acute and chronic pain models without interfering with GLP-1R function. Our study revealed a novel role for GLP-1 and its derivatives in pain relief, proposing exendin 20-29 as a promising therapeutic candidate.

Inactivation of Cronobacter sakazakii in powdered infant formula with probiotics and metagenomic analysis.

In the present study, proper manual for powdered infant formula with probiotics (PIF-P) to prevent the contamination of Cronobacter sakazakii was investigated. First, the population of C. sakazakii and LAB in three different PIF-P samples were quantitatively analyzed after reconstituted with hydrothermal treatments. When C. sakazakii was inoculated into reconstituted infant formula with probiotics (RIF-P), it was immediately reduced below the detection limit by 60-65 °C hydrothermal treatment whereas reduction levels of LAB was 1-2 log CFU/g. When heat resistance of C. sakazakii inoculated to PIF-P with 4 h drying was compared with that inoculated to RIF-P samples, the heat resistance of C. sakazakii increased significantly after the inoculation in PIF-P with drying. Metagenomic analysis revealed that Lactobacillus and Bifidobacterium were dominant genus in all three groups and there was no significant difference in the microbial community of untreated PIF sample and hydrothermal treated samples. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01503-x.

Orthodontic diagnosis rates based on panoramic radiographs in children aged 6-8 years: A retrospective study.

Objective: This study aimed to retrospectively analyze the prevalence of orthodontic problems and the proportion of patients who underwent orthodontic diagnosis among children aged 6 (n = 300), 7 (n = 400), and 8 (n = 400) years who had undergone panoramic radiography. Methods: Children were divided into five groups according to their chief complaint and consultation: conservative dentistry, oral and maxillofacial surgery, orthodontics, periodontics, and prosthodontics). Chief complaints investigated included first molar eruption, lack of space for incisor eruption, frequency of eruption problems, lack of space, impaction, supernumerary teeth (SNT), missing teeth, and ectropion eruption. The number of patients whose chief complaint was not related to orthodontics but had dental problems requiring orthodontic treatment was counted. The proportion of patients with orthodontic problems who received an orthodontic diagnosis was also examined. Results: Dental trauma and SNT were the most frequent chief complaints among the children. The proportion of patients with orthodontic problems increased with age. However, the orthodontic diagnosis rates based on panoramic radiographs among children aged 6, 7, 8 years were only 1.5% (6 years) and 23% (7 and 8 years). Conclusions: Accurate information should be provided to patient caregivers to correct misconceptions regarding the appropriateness of delaying orthodontic examination until permanent dentition is established.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

Imeglimin attenuates NLRP3 inflammasome activation by restoring mitochondrial functions in macrophages.

Imeglimin is a novel oral antidiabetic drug for treating type 2 diabetes. However, the effect of imeglimin on NLRP3 inflammasome activation has not been investigated yet. Here, we aimed to investigate whether imeglimin reduces LPS-induced NLRP3 inflammasome activation in THP-1 macrophages and examine the associated underlying mechanisms. We analyzed the mRNA and protein expression levels of NLRP3 inflammasome components and IL-1ß secretion. Additionally, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening were measured by flow cytometry. Imeglimin inhibited NLRP3 inflammasome-mediated IL-1ß production in LPS-stimulated THP-1-derived macrophages. In addition, imeglimin reduced LPS-induced mitochondrial ROS production and mitogen-activated protein kinase phosphorylation. Furthermore, imeglimin restored the mitochondrial function by modulating mitochondrial membrane depolarization and mPTP opening. We demonstrated for the first time that imeglimin reduces LPS-induced NLRP3 inflammasome activation by inhibiting mPTP opening in THP-1 macrophages. These results suggest that imeglimin could be a promising new anti-inflammatory agent for treating diabetic complications.

Maximization strategies in relationship and career enhances life satisfaction through meaning making among established adults in South Korea.

BACKGROUND: Choosing a partner and job have long been regarded as important developmental milestones to reach in adulthood. In a collective cultural context with high familial and societal expectations to commit to a relationship and job by age 30, maximizing on such life decisions might potentially harm one's well-being. The literature on maximization-well-being association is complex, and recent research suggests that this relationship might differ by its dimensions and cultural context. In the present study, we examined how engaging in a maximization strategy in relationship and career domains predicts life satisfaction and whether this pathway is mediated by a meaning-making process (search-to-presence of meaning) among established adults in South Korea. METHODS: Survey data on measures of relational maximization strategy, career maximization strategy, search for meaning, presence of meaning, and life satisfaction was collected from 264 South Korean unmarried, working adults in their 30 s to 40 s. A two-step structural equation modeling method was applied to test the hypothesized serial mediation model. RESULTS: Tests of the measurement and structural model showed good fit with the data (CFI = .96, TLI = .95, RMSEA = .07, SRMR = .05). Further bootstrapping results supported significant indirect effects of the serial mediation model in the paths between maximization strategy and life satisfaction via a search-to-presence of meaning in both relational (b = .16, 95% CI [.01, -.16], p < .05) and career (b = .26, 95% CI [.11, -.26], p < .01) domains. CONCLUSIONS: Our findings suggest that for established adults in a collectivist culture who may experience familial and social pressure on these life choices, searching for alternative options to make the best relationship and career decisions could potentially lead to higher life satisfaction, when done through an intentional meaning-making process.

Clinical and Microbiologic Analysis of Klebsiella pneumoniae Infection: Hypermucoviscosity, Virulence Factor, Genotype, and Antimicrobial Susceptibility.

Hypervirulent Klebsiella pneumoniae (KP) is defined according to hypermucoviscosity or various virulence factors and is clinically associated with community-acquired liver abscess (CLA). In this study, we investigated the clinical and microbiological characteristics of KP and significant factors associated with hypervirulence. The clinical characteristics, antimicrobial susceptibility, hypermucoviscosity, serotypes, hypervirulence-related genes, and biofilm formation of 414 KP isolates collected from the Keimyung University Dongsan Hospital between December 2013 and November 2015 were analyzed according to CLA. Significant risk factors for hypervirulent KP (HvKP) associated with CLA were investigated using logistic regression analysis. Notably, 155 (37.4%) isolates were hypermucoviscous, and 170 (41.1%) harbored aerobactin. CLA was present in 34 cases (8.2%). Epidemiology and treatment outcomes did not differ significantly between the CLA and non-CLA groups. The CLA group had significantly higher antibiotic susceptibility, K1/K2, rmpA, magA, allS, kfu, iutA, string test-positive result, and biofilm mass. Multivariate logistic regression revealed rmpA (OR, 5.67; 95% CI, 2.09-15.33; p = 0.001), magA (OR, 2.34; 95% CI, 1.01-5.40; p = 0.047), and biofilm mass >0.80 (OR, 2.13; 95% CI, 1.00-4.56; p = 0.050) as significant risk factors for CLA. rmpA was identified as the most significant risk factor for CLA among KP strains, implying that it is an important factor associated with HvKP.

Systematic Engineering of Genistein Biosynthetic Pathway through Genetic Regulators and Combinatorial Enzyme Screening.

Microbial production of genistein, an isoflavonoid primarily found in soybeans, is gaining prominence in the food industry due to its significant nutritional and health benefits. However, challenges arise in redesigning strains due to intricate regulatory nodes between cell growth and genistein production and in systematically exploring core enzymes involving genistein biosynthesis. To address this, this study devised a strategy that simultaneously and precisely rewires flux at both acetyl-CoA and malonyl-CoA nodes toward genistein synthesis. In particular, naringenin, the primary precursor of genistein, was accumulated 2.6 times more than the unoptimized strain through transcriptional repressor-based genetic regulators. Building upon this, a combination of isoflavone synthase and cytochrome P450 reductase with the remarkable conversion of naringenin to genistein was screened from enzyme homologue libraries. The integrated metabolic engineering strategy yields the highest reported production (98 mg/L of genistein) to date, providing a framework for the biosynthesis of diverse flavonoids, including genistein.