Fracture Strength of Six-Unit Anterior Fixed Provisional Restorations Fabricated Using Various Dental CAD/CAM Systems.

PURPOSE: This study compares the fracture strengths of long-span fixed provisional restorations fabricated via digital additive and subtractive methods to those fabricated via conventional heat-processing techniques. MATERIALS AND METHODS: A six-unit anterior partial restoration was designed as an anatomical and morphologic structure using a dental CAD/CAM system. The provisional restorations (N = 40) of four different fabrication methods (n = 10 per group) were used for the failure loading test: stereolithography apparatus (SLA), liquid crystal display (LCD), milling (MIL), and heat-processed temporary (HPT). The specimens were subjected to a maximum load-to-fracture test using a universal testing machine, and the representative fracture patterns were observed. Statistical analysis was performed using Shapiro-Wilk, Kruskal-Wallis, Mann-Whitney U, and Bonferroni post hoc tests (P < .05). RESULTS: The four groups showed significant differences in fracture strength according to the materials and manufacturing methods used (P < .001, except between SLA and HPT groups). The fracture strengths of MIL and LCD digitally fabricated groups were significantly higher than that of the HPT group (P < .001). CONCLUSIONS: The subtractive method is ideal for fabricating long-span fixed provisional restorations for long-term use. Additionally, LCD additive manufacturing technology could soon be a good alternative for restorations.

Long-term prognostic factors for cardiovascular events in patients with chest pain without diabetes mellitus nor significant coronary stenosis.

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), revascularization, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal antianginal medication therapy. However, a recurrent chest pain remains a problem even with continuous antianginal medication therapy. Up to 5 years, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia (HR: 2.010, 95% CI 1.166-3.466, P = 0.012), mild-moderate (30-70%) coronary stenosis (HR: 2.369, 95% CI 1.118-5.018, P = 0.024), the use of aspirin (HR: 2.885, 95% CI 1.588-5.238, P < 0.001), and the use of nitrates (HR: 1.938, 95% CI 1.094-3.433, P = 0.023) were independent risk factors for MACCE. Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with antianginal medications.

Long-term air pollution exposure is associated with higher incidence of ST-elevation myocardial infarction and in-hospital cardiogenic shock.

Previous studies have reported the association between myocardial infarction (MI) and air pollution (AP). However, limited information is available regarding the long-term effects of AP on the relative incidence rates of ST-elevation MI (STEMI) and Non-ST-elevation MI (NSTEMI). We investigated the association between long-term exposure to AP and the incidence of STEMI. Between January 2006 and December 2015, a total of 45,619 eligible patients with Acute Myocardial Infarction (AMI) were enrolled in the Korea Acute MI Registry (KAMIR) and KAMIR-National Institutes of Health. Mixed-effect regression models were used to examine the association between the annual average ambient AP before MI onset and the incidence of STEMI, and to evaluate the association of AP with the incidence of in-hospital cardiogenic shock. After mixed-effect regression model analysis, particulate matter (PM) 10 µm or less in diameter (PM10) was associated with increased incidence of STEMI compared with NSTEMI (odds ratio [OR] 1.009, 95% Confidence Interval [CI] 1.002-1.016; p = 0.012). For in-hospital cardiogenic shock complication, PM10 and SO2 were associated with increased risk, PM10 (OR 1.033, 95% CI 1.018-1.050; p < 0.001), SO2 (OR 1.104, 95% CI 1.006-1.212; p = 0.037), respectively. Policy-level strategies and clinical efforts to reduce AP exposure are necessary to prevent the incidence of STEMI and severe cardiovascular complications.

Promising Effect of the Children in Disaster: Evaluation and Recovery Intervention on Trauma Symptoms and Quality of Life for Children and Adolescents: A Controlled Study.

OBJECTIVE: The Children in Disaster: Evaluation and Recovery (CIDER) program in Korea was developed to treat children and adolescents exposed to trauma. This study aimed to demonstrate the effectiveness of the CIDER through a comparison with controls. METHODS: A total of 85 participants consisted of the intervention group (n=41) and control group (n=44). We assessed the changes in trauma-related symptoms, depression, anxiety, and improvements in quality of life before and after the intervention. RESULTS: In total, bullying and school violence (44.7%) were the most common trauma, followed by sexual abuse (17.6%). Acute stress disorder and post-traumatic stress disorder (PTSD) accounted for 41.2%, and attention-deficit/hyperactivity disorder (ADHD) and developmental disorder were the most common comorbidities (51.8%). The symptoms of trauma, depression, anxiety, and quality of life improved significantly in the intervention group, while the control group did not show significant changes. CONCLUSION: Compared with the control group, the CIDER improved symptoms and quality of life in children and adolescents who had experienced trauma. The CIDER program was practical and easy to apply, even for different ages, types of traumas, and comorbidities.

Biofilm removal effect of diatom complex on 3D printed denture base resin.

For patients who have difficulty in mechanical cleaning of dental appliances, a denture cleaner that can remove biofilm with dense extracellular polymeric substances is needed. The purpose of this study is to evaluate the efficacy of diatom complex with active micro-locomotion for removing biofilms from 3D printed dentures. The diatom complex, which is made by doping MnO2 nanosheets on diatom biosilica, is mixed with H2O2 to generate fine air bubbles continuously. Denture base resin specimens were 3D printed in a roof shape, and Pseudomonas aeruginosa (107 CFU/mL) was cultured on those for biofilm formation. Cleaning solutions of phosphate-buffered saline (negative control, NC), 3% H2O2 with peracetic acid (positive control, PC), denture cleanser tablet (DCT), 3% H2O2 with 2 mg/mL diatom complex M (Melosira, DM), 3% H2O2 with 2 mg/mL diatom complex A (Aulacoseira, DA), and DCT with 2 mg/mL DM were prepared and applied. To assess the efficacy of biofilm removal quantitatively, absorbance after cleaning was measured. To evaluate the stability of long-term use, surface roughness, ΔE, surface micro-hardness, and flexural strength of the 3D printed dentures were measured before and after cleaning. Cytotoxicity was evaluated using Cell Counting Kit-8. All statistical analyses were conducted using SPSS for Windows with one-way ANOVA, followed by Scheffe's test as a post hoc (p < 0.05). The group treated with 3% H2O2 with DA demonstrated the lowest absorbance value, followed by the groups treated with 3% H2O2 with DM, PC, DCT, DCT + DM, and finally NC. As a result of Scheffe's test to evaluate the significance of difference between the mean values of each group, statistically significant differences were shown in all groups based on the NC group. The DA and DM groups showed the largest mean difference though there was no significant difference between the two groups. Regarding the evaluation of physical and mechanical properties of the denture base resin, no statistically significant differences were observed before and after cleaning. In the cytotoxicity test, the relative cell count was over 70%, reflecting an absence of cytotoxicity. The diatom complex utilizing active micro-locomotion has effective biofilm removal ability and has a minimal effect in physical and mechanical properties of the substrate with no cytotoxicity.

Non-suicidal Self-injury and Quantified Electroencephalogram in Adolescents and Young Adults with Depression.

Objective: : This study investigated the association between non-suicidal self-injury (NSSI) and quantified electroencephalogram (QEEG) in patients with depression. We aimed to identify clinical features of NSSI and differences in QEEG findings. Methods: : This retrospective study used the medical records of 52 inpatients with major depressive episodes, aged from 15 to 30. The patients were categorized according to their history of NSSI. Their main diagnosis and sex were also considered. To evaluate clinical symptoms, self-reported scales were used. The absolute power and the Z-scores of various waves were included. Results: : NSSI was associated with suicidal ideations (p = 0.001) and trauma history (p = 0.014). In the binary logistic regression analysis, the Z-score of absolute alpha power was higher on the FP2 node (p = 0.029), lower on the F4 node (p = 0.029) in the NSSI group. The absolute high beta power in the NSSI group was higher on the FP2 and the F3 node, but lower on the F7 and F8 node. Patients with NSSI showed higher Z-score of the absolute delta power at the FP2 node (p = 0.044). The absolute gamma power was higher on the FP2 (p = 0.012) and the F3 node (0.043), lower on the FP1 (p = 0.019) and the F7 node (0.018) in the NSSI group. The absolute high gamma power at the FP2 (p = 0.017) and F8 nodes (p = 0.045) were higher in the NSSI group. Conclusion: : Patients with NSSI may have clinical features distinct from those of patients without NSSI. QEEG results have shown some differences, although it is less applicable due to some limitations.

Role of GO and Photoinitiator Concentration on Curing Behavior of PEG-Based Polymer for DLP 3D Printing.

Photocuring kinetics in photopolymerization-based three-dimensional (3D) printing processes have gained significant attention because they determine the final dimension accuracy of the printed structures. In this study, the curing kinetics of liquid-light-curable resins, including water-dispersed graphene oxide (GO) and ultraviolet (UV)-cured acrylic resins, were investigated during digital light processing (DLP) 3D printing. Various stable composites of water-dispersed GO and UV-cured acrylic resin were prepared to fabricate 3D structures for cure-depth measurements. Several factors, including the UV-exposure conditions, photoinitiator concentration, and composition of the photopolymer resin, were found to significantly affect the cure-depth characteristics of the printed structures. The photocuring depth of the polymeric resin system was investigated as a function of the photoinitiator concentration. In addition, the study showed that the introduction of GO played a significant role in controlling the performance of the highly cross-linked network and the thickness of the cured layer. The curing characteristics of functional photocurable polymer-based DLP 3D printing contribute to process development and improvement of the quality of printed microstructures for industrial applications.

Pb2+ Ion Sensors Employing Gold Etching Process: Comparative Investigation on Au Nanorods and Au Nanotriangles.

The leaching phenomenon of gold (Au) nanomaterials by Pb2+ ions in the presence of 2-mercaptoethanol (2-ME) and thiosulfate (S2O32- ion) has been systematically applied to a Pb2+ ion sensor. To further investigate the role of Pb2+ ions in sensors containing Au nanomaterials, we revisited the leaching conditions for Au nanorods and compared them with the results for Au nanotriangles. By monitoring the etching rate, it was revealed that Pb2+ ions were important for the acceleration of the etching rate mainly driven by 2-ME and S2O32- pairs, and nanomolar detection of Pb2+ ions were shown to be promoted through this catalytic effect. Using the etchant, the overall size of the Au nanorods decreased but showed an unusual red-shift in UV-Vis spectrum indicating increase of aspect ratio. Indeed, the length of Au nanorods decreased by 9.4% with the width decreasing by 17.4% over a 30-min reaction time. On the other hand, the Au nanotriangles with both flat sides surrounded mostly by dense Au{111} planes showed ordinary blue-shift in UV-Vis spectrum as the length of one side was reduced by 21.3%. By observing the changes in the two types of Au nanomaterials, we inferred that there was facet-dependent alloy formation with lead, and this difference resulted in Au nanotriangles showing good sensitivity, but lower detection limits compared to the Au nanorods.

Quantitative Association between Computed-Tomography-Based L1 Skeletal Muscle Indices and Major Adverse Clinical Events Following Percutaneous Coronary Intervention.

Sarcopenia is as a non-traditional risk factor for atherosclerotic cardiovascular disease. Further investigation is required to elucidate the prognostic significance of computed tomography (CT)-based sarcopenia assessment in coronary artery disease (CAD). We prospectively enrolled 475 patients, who underwent coronary stent implantation and peri-procedural CT scans within one month. Skeletal muscle index (SMI) was assessed cross-sectionally at the first lumbar vertebra (L1) level. The participants were grouped based on sex-specific L1 SMI quartiles. The primary endpoint was all-cause mortality, and the secondary composite endpoint was major adverse cardiovascular events (MACEs) over a 3-year follow-up period. Three-year all-cause mortality and MACE incidence increased significantly in patients in the lower L1 SMI quartiles compared to those of patients in the higher quartiles (p < 0.001). The individual composite endpoints consistently showed a higher incidence in the lower quartiles of L1 SMI (p < 0.001). In multivariable analysis, the lower L1 SMI quartiles independently predicted 3-year all-cause mortality and MACEs (lowest vs. highest quartiles, respectively: OR 4.90 (95% CI 1.54-15.5), p = 0.007; and OR 12.3 (95% CI 4.99-30.4), p < 0.001). In conclusion, CT-based L1 SMI demonstrated a distinct dose-dependent relationship with future MACEs in CAD patients undergoing percutaneous coronary intervention, thereby enhancing cardiovascular risk stratification.

Metabolite Profiling of Allium hookeri Leaves Using UHPLC-qTOF-MS/MS and the Senomorphic Activity of Phenolamides.

The plant Allium hookeri, a member of the Allium genus, has a rich history of culinary and medicinal use. Recent studies have unveiled its potent antioxidant and anti-inflammatory properties. While research on A. hookeri has demonstrated its neuroprotective and anti-neuroinflammatory effects, the specific bioactive compounds responsible for these effects remain unidentified in prior research. This study utilized an untargeted metabolomic approach, employing HRESI-qTOF MS/MS-based molecular networking, to comprehensively profile the chemical composition of metabolites in A. hookeri and identify new compounds within the plant. As a result, ten compounds, comprising one novel flavonoid (2) and nine known compounds (1 and 3-10), were isolated and identified through NMR analysis. The inhibitory effects of all isolated compounds on the senescent cell-associated secretory phenotype (SASP), which is pivotal in neuroprotective actions, were evaluated. Biological activity testing revealed N-trans-feruloyltyramine (7) to be the most potent compound, effectively inhibiting SASP markers and contributing to the senomorphic activities of A. hookeri. These findings underscore the potential of phenolamides from A. hookeri as a promising source of bioactive compounds for mitigating senescence-associated diseases.

Oxindole and Benzoxazinone Alkaloids from the Seeds of Persea americana (Avocado) and Their SIRT1 Stimulatory Activity.

Persea americana Mill. (Lauraceae), commonly known as avocado, is a well-known food because of its nutrition and health benefits. The seeds of avocado are major byproducts, and thus their phytochemicals and bioactivities have been of interest for study. The chemical components of avocado seeds were investigated by using UPLC-qTOF-MS/MS-based molecular networking, resulting in the isolation of seven new oxindole alkaloids (1-7) and two new benzoxazinone alkaloids (8 and 9). The chemical structures of the isolated compounds were identified by the analysis of NMR data in combination with computational approaches, including NMR and ECD calculations. Bioactivities of the isolated compounds toward silent information regulation 2 homologue-1 (SIRT1) in HEK293 cells were assessed. The results showed that compound 1 had the most potent effect on SIRT1 activation with an elevated NAD+/NADH ratio with potential for further investigation as an anti-aging agent.

Long-term clinical outcomes following successful percutaneous coronary intervention in patients with extremely long coronary chronic total occlusion lesions.

BACKGROUND: Lesion length is related to worse clinical outcomes following percutaneous coronary intervention (PCI) for the treatment of chronic total occlusion (CTO). However, the data to confirm the association between extremely long lesions and clinical hard endpoints have been limited. Therefore, we investigated the impact of extremely long CTO lesions (≥50 mm, treated lesion length) on the long-term clinical outcomes following successful PCI. METHODS: A total of 333 consecutive patients with CTO who underwent successful PCI with drug-eluting stents (DESs) were allocated to either the extremely long or the short CTO group according to their CTO lesion length. The 5-year clinical outcomes were compared between the two groups. The incidence of myocardial infarction, cardiac death (CD), revascularization, and major adverse cardiovascular events (MACE) was higher in the extremely long CTO group. The 5-year clinical outcomes were analyzed using the Cox hazard ratio (HR) model. RESULTS: In the entire study population, the extremely long CTO lesion was an independent predictor for higher rate of revascularization, MACE, CD, or mortality. CONCLUSIONS: In our study, CTO patients with extremely long lesions (≥50 mm) who underwent successful PCI were associated with a higher risk of worse long-term clinical outcomes, including hard clinical endpoints such as CD and mortality even in the DESs era.

Linderanidins A-F: Rare oligomeric flavonoids with an unusual C-3-C-4 linkage from the roots of Lindera erythrocarpa and their inhibitory activities on autophagy.

Autophagy is a crucial process for maintaining cellular homeostasis by degrading and recycling unnecessary or damaged cellular components. In the process of exploring autophagy regulators in plants, unique nine oligomeric flavonoids linked by the bonding of C-3 and C-4, consisting of three pairs of biflavonoids, linderanidins A-C [(+)-1/(-)-1, (+)-2/(-)-2, and (+)-3/(-)-3], and three trimeric A-type proanthocyanidins, linderanidins D-F (4-6), were isolated from the roots of Lindera erythrocarpa. The structures and absolute configurations of these compounds were determined using various techniques, such as 1D and 2D NMR, mass spectrometry, X-ray crystallography, and electronic circular dichroism. All isolates were evaluated for their ability to regulate autophagy, and compounds (±)-1-(±)-3, (-)-1-(-)-3, (+)-1-(+)-3 and 4 were found to inhibit autophagy by blocking the fusion process between autophagosome and lysosome in HEK293 cells. This study suggests that unique oligomeric flavonoids possessing a C-3-C-4 linkage derived from the roots of L. erythrocarpa are potent autophagy inhibitors.

Itaconate family-based host-directed therapeutics for infections.

Itaconate is a crucial anti-infective and anti-inflammatory immunometabolite that accumulates upon disruption of the Krebs cycle in effector macrophages undergoing inflammatory stress. Esterified derivatives of itaconate (4-octyl itaconate and dimethyl itaconate) and its isomers (mesaconate and citraconate) are promising candidate drugs for inflammation and infection. Several itaconate family members participate in host defense, immune and metabolic modulation, and amelioration of infection, although opposite effects have also been reported. However, the precise mechanisms by which itaconate and its family members exert its effects are not fully understood. In addition, contradictory results in different experimental settings and a lack of clinical data make it difficult to draw definitive conclusions about the therapeutic potential of itaconate. Here we review how the immune response gene 1-itaconate pathway is activated during infection and its role in host defense and pathogenesis in a context-dependent manner. Certain pathogens can use itaconate to establish infections. Finally, we briefly discuss the major mechanisms by which itaconate family members exert antimicrobial effects. To thoroughly comprehend how itaconate exerts its anti-inflammatory and antimicrobial effects, additional research on the actual mechanism of action is necessary. This review examines the current state of itaconate research in infection and identifies the key challenges and opportunities for future research in this field.

Accuracy of Measurements of the Structural Reserve for Upper Limb Function in Patients With Moderate-to-Severe Stroke.

BACKGROUND: The structural integrity of the corticospinal tract (CST) is an important biomarker of poststroke upper limb recovery. Injured CST undergoes Wallerian degeneration rostrocaudally during the first few months. However, there is no standardized measurement of the structural integrity of the CST. This study aimed to determine the measurement accuracy of the structural integrity of the CST. METHODS: This cross-sectional study included 50 consecutive patients with middle cerebral artery stroke who underwent diffusion tensor imaging upon transfer from the acute stroke unit to the inpatient rehabilitation facility (2018-2022). We evaluated hemiplegic upper limb function using Shoulder Abduction and Finger Extension (SAFE) scores. Fractional anisotropy values representing the structural integrity of the CST were evaluated using 4 region of interest-based and 2 tract-based measurements, including the posterior limb of internal capsule, cerebral peduncle, pons, pontomedullary junction, entire CST, and CST in the brainstem. Multivariate linear regression models and the area under the curve (AUC) were used to determine measurement accuracy for hemiplegic upper limb function. RESULTS: The structural integrity of the CST at the pontomedullary junction showed the highest explanatory power, followed by the entire CST, in the multivariate linear regression models (adjusted R2=0.459 and 0.425, respectively). The structural integrity of the CST at the pontomedullary junction also showed the highest AUC, followed by the entire CST, in discriminating patients with a SAFE score of <8 or 5 from those with SAFE ≥8 or 5 (SAFE <8: AUC, 0.90 [95% CI, 0.80-1.00]; AUC, 0.83 [0.66-0.99]; SAFE <5: AUC, 0.87 [0.77-0.96]; AUC, 0.83, [0.72-0.95], respectively). CONCLUSIONS: The structural integrity of the CST measured at the pontomedullary junction or entire CST demonstrated the highest accuracy for hemiplegic upper limb function in the subacute phase of stroke.

Development and validation of equation for cardiorespiratory fitness in patients with heart failure with preserved ejection fraction.

BACKGROUND/AIMS: Cardiorespiratory fitness (CRF), as measured by maximal oxygen consumption (VO2max), is an important independent predictive factor of cardiovascular outcomes in patients with heart failure (HF). However, it is unclear whether conventional equations for estimating CRF are applicable to patients with HF with preserved ejection fraction (HFpEF). METHODS: This study included 521 patients with HFpEF (EF ≥ 50%) whose CRF was directly measured by cardiopulmonary exercise test using a treadmill. We developed a new equation (Kor-HFpEF) for half of the patients in the HFpEF cohort (group A, n = 253) and validated it for the remaining half (group B, n = 268). The accuracy of the Kor-HFpEF equation was compared to that of the other equations in the validation group. RESULTS: In the total HFpEF cohort, the directly measured VO2max was significantly overestimated by the FRIEND and ACSM equations (p < 0.001) and underestimated by the FRIEND-HF equation (p <0.001) (direct 21.2 ± 5.9 mL/kg/min; FRIEND 29.1 ± 11.8 mL/kg/min; ACSM 32.5 ± 13.4 mL/kg/min; FRIEND-HF 14.1 ± 4.9 mL/kg/min). However, the VO2max estimated by the Kor-HFpEF equation (21.3 ± 4.6 mL/kg/min) was similar to the directly measured VO2max (21.7 ± 5.9 mL/kg/min, p = 0.124), whereas the VO2max estimated by the other three equations was still significantly different from the directly measured VO2max in group B (all p < 0.001). CONCLUSION: Traditional equations used to estimate VO2max were not applicable to patients with HFpEF. We developed and validated a new Kor-HFpEF equation for these patients, which had a high accuracy.

Chemical constituents with senolytic activity from the stems of Limacia scandens.

While screening senotherapeutics from natural products, seven undescribed chemicals, two syringylglycerol derivatives, two cyclopeptides, one tigliane analogue, and two chromone derivatives, as well as six known compounds were isolated from the stems of Limacia scandens. The structures of compounds were elucidated through spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, and CD data. All compounds were tested in replicative senescent human dermal fibroblasts (HDFs) to determine their potential as senotherapeutic agents to specifically target senescent cells. One tigliane and two chromones derivatives showed senolytic activity, indicating that senescent cells were selectively removed. Especially, 2-{2-[(3'-O-ß-d-glucopyranosyl)phenyl]ethyl}chromone is expected to be a potential senotherapeutics by inducing HDF death, inhibiting the activity of senescence-associated ß-galactosidase (SA-ß-gal) and expressing senescence-associated secretory phenotype (SASP) factors.

Composition and variability of core phyllosphere fungal mycobiota on field-grown broccoli.

BACKGROUND: Fresh vegetables harbor an assemblage of different microorganisms on their surfaces. The phyllosphere microbiota is important for maintaining plant health and managing crop quality before and after harvest. However, the diversity and ecology of fungal communities are largely unexplored in fresh vegetables. This study investigated the phyllosphere mycobiota of field-grown broccoli florets (n = 66) collected from 22 farms across four regions in Korea, using culturing, amplicon sequencing of the internal transcribed spacer region, and microbial network analysis. RESULTS: Microbial network analysis identified core genera (Purpureocillium, Filobasidium, Cystofilobasidium, Papiliotrema, Aureobasidium, and unclassified genera of Capnodiales) specific to the broccoli phyllosphere. The composition and network complexity of core and unique populations varied among farming regions, and was associated with local agro-meteorological conditions. The complexity of microbial associations was higher in mature communities than in immature communities, but complexity was lost upon development of plant pathogenic disease. Broccoli mycobiota were classified according to the dominance of Purpurecillium. While Purpurecillium-type microbiota were prevalent in normal samples, Filobasidium-type microbiota were frequently observed in immature, damaged, or postharvest samples. CONCLUSIONS: Together, fungal communities were important components of phyllosphere microbiota on fresh vegetables, and have substantial potential for exploitation to enhance and stabilize plant health and growth.

Dimethyl itaconate is effective in host-directed antimicrobial responses against mycobacterial infections through multifaceted innate immune pathways.

BACKGROUND: Itaconate, a crucial immunometabolite, plays a critical role in linking immune and metabolic functions to influence host defense and inflammation. Due to its polar structure, the esterified cell-permeable derivatives of itaconate are being developed to provide therapeutic opportunities in infectious and inflammatory diseases. Yet, it remains largely uncharacterized whether itaconate derivatives have potentials in promoting host-directed therapeutics (HDT) against mycobacterial infections. Here, we report dimethyl itaconate (DMI) as the promising candidate for HDT against both Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria by orchestrating multiple innate immune programs. RESULTS: DMI per se has low bactericidal activity against Mtb, M. bovis Bacillus Calmette-Guérin (BCG), and M. avium (Mav). However, DMI robustly activated intracellular elimination of multiple mycobacterial strains (Mtb, BCG, Mav, and even to multidrug-resistant Mtb) in macrophages and in vivo. DMI significantly suppressed the production of interleukin-6 and -10, whereas it enhanced autophagy and phagosomal maturation, during Mtb infection. DMI-mediated autophagy partly contributed to antimicrobial host defenses in macrophages. Moreover, DMI significantly downregulated the activation of signal transducer and activator of transcription 3 signaling during infection with Mtb, BCG, and Mav. CONCLUSION: Together, DMI has potent anti-mycobacterial activities in macrophages and in vivo through promoting multifaceted ways for innate host defenses. DMI may bring light to new candidate for HDT against Mtb and nontuberculous mycobacteria, both of which infections are often intractable with antibiotic resistance.