One-Year Results of Ear Reconstruction with 3D Printed Implants.

PURPOSE: External ear reconstruction has been a challenging subject for plastic surgeons for decades. Popular methods using autologous costal cartilage or polyethylene still have their drawbacks. With the advance of three-dimensional (3D) printing technique, bioscaffold engineering using synthetic polymer draws attention as an alternative. This is a clinical trial of ear reconstruction using 3D printed scaffold, presented with clinical results after 1 year. MATERIALS AND METHODS: From 2021 to 2022, five adult patients with unilateral microtia underwent two-staged total ear reconstruction using 3D printed implants. For each patient, a patient-specific 3D printed scaffold was designed and produced with polycaprolactone (PCL) based on computed tomography images, using fused deposition modeling. Computed tomography scan was obtained preoperatively, within 2 weeks following the surgery and after 1 year, to compare the volume of the normal side and the reconstructed ear. At 1-year visit, clinical photo was taken for scoring by two surgeons and patients themselves. RESULTS: All five patients had completely healed reconstructed ear at 1-year follow-up. On average, the volume of reconstructed ear was 161.54% of that of the normal side ear. In a range of 0 to 10, objective assessors gave scores 3 to 6, whereas patients gave scores 8 to 10. CONCLUSION: External ear reconstruction using 3D printed PCL implant showed durable, safe results reflected by excellent volume restoration and patient satisfaction at 1 year postoperatively. Further clinical follow-up with more cases and refinement of scaffold with advancing bioprinting technique is anticipated. The study's plan and results have been registered with the Clinical Research Information Service (CRIS No. 3-2019-0306) and the Ministry of Food and Drug Safety (MFDS No. 1182).

A Pilot Study for Effectiveness and Safety of Adjunctive Pharmacopuncture to Acupuncture Treatment for Rotator Cuff Diseases: A Pragmatic Randomized Controlled Trial.

Purpose: Pharmacopuncture therapy has been used in the conservative treatment of rotator cuff disease adjuvant to acupuncture treatment. Despite the increasing utilization of pharmacopuncture therapy, there is still a lack of high-quality research to support its effectiveness. This pilot study aimed to assess the feasibility of pharmacopuncture therapy adjuvant to acupuncture treatment for rotator cuff disease. Patients and Methods: This was a parallel-grouped, pragmatic randomized controlled, pilot study. Forty patients were randomly allocated to either the experimental or the control group. All patients received acupuncture treatment for four weeks, and pharmacopuncture was additionally administered to the experimental group. After eight treatments were delivered over four weeks, follow-up assessments were performed. The primary outcome was the mean change in the visual analog scale (VAS) score for shoulder pain from baseline to visit 8. Secondary outcomes included shoulder pain and disability index (SPADI) at visits 4, 8, and 9, shoulder range of motion (ROM) at visits 4, 8, and 9, EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) at visits 8 and 9, patient global impression of change (PGIC) at visits 8 and 9, and mean rescue medication consumption at visits 8 and 9. Results: Both groups showed that each treatment effectively improved rotator cuff disease in most assessments. Particularly, the group that received acupuncture plus pharmacopuncture required fewer rescue medications than the group that received acupuncture alone. However, there was little statistically significant difference between the two groups. There were no serious adverse events experienced by patients in this study. Conclusion: Although there was little statistical difference between the two groups, the combination of acupuncture and pharmacopuncture for rotator cuff disease was associated with a reduction in the rescue medicine dosage compared with acupuncture alone. Also, it confirmed the safety of pharmacopuncture therapy. This pilot study would help design future research on the effectiveness of pharmacopuncture in rotator cuff disease.

In Situ Hydrogel with Immobilized Mn-Porphyrin for Reactive Oxygen Species Scavenging, Oxygen Generation, and Risedronate Delivery in Bone Defect Treatment.

We propose a hydrogel immobilized with manganese porphyrin (MnP), a biomimetic superoxide dismutase (SOD), and catalase (CAT) to modulate reactive oxygen species (ROS) and hypoxia that impede the repair of large bone defects. Our hydrogel synthesis involved thiolated chitosan and polyethylene glycol-maleimide conjugated with MnPs (MnP-PEG-MAL), which enabled in situ gelation via a click reaction. Through optimization, a hydrogel with mechanical properties and catalytic effects favorable for bone repair was selected. Additionally, the hydrogel was incorporated with risedronate to induce synergistic effects of ROS scavenging, O2 generation, and sustained drug release. In vitro studies demonstrated enhanced proliferation and differentiation of MG-63 cells and suppressed proliferation and differentiation of RAW 264.7 cells in ROS-rich environments. In vivo evaluation of a calvarial bone defect model revealed that this multifunctional hydrogel facilitated significant bone regeneration. Therefore, the hydrogel proposed in this study is a promising strategy for addressing complex wound environments and promoting effective bone healing.

Development and external validation of a logistic and a penalized logistic model using machine-learning techniques to predict suicide attempts: A multicenter prospective cohort study in Korea.

Despite previous efforts to build statistical models for predicting the risk of suicidal behavior using machine-learning analysis, a high-accuracy model can lead to overfitting. Furthermore, internal validation cannot completely address this problem. In this study, we created models for predicting the occurrence of suicide attempts among Koreans at high risk of suicide, and we verified these models in an independent cohort. We performed logistic and penalized regression for suicide attempts within 6 months among suicidal ideators and attempters in The Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS). We then validated the models in a test cohort. Our findings indicated that several factors significantly predicted suicide attempts in the models, including young age, suicidal ideation, previous suicidal attempts, anxiety, alcohol abuse, stress, and impulsivity. The area under the curve and positive predictive values were 0.941 and 0.484 after variable selection and 0.751 and 0.084 in the test cohort. The corresponding values for the penalized regression model were 0.943 and 0.524 in the original training cohort and 0.794 and 0.115 in the test cohort. The prediction model constructed through a prospective cohort study of the suicide high-risk group showed satisfactory accuracy even in the test cohort. The accuracy with penalized regression was greater than that with the "classical" logistic model.

Evolving Paradigms in Sepsis Management: A Narrative Review.

Sepsis, a condition characterized by life-threatening organ dysfunction due to a dysregulated host response to infection, significantly impacts global health, with mortality rates varying widely across regions. Traditional therapeutic strategies that target hyperinflammation and immunosuppression have largely failed to improve outcomes, underscoring the need for innovative approaches. This review examines the development of therapeutic agents for sepsis, with a focus on clinical trials addressing hyperinflammation and immunosuppression. It highlights the frequent failures of these trials, explores the underlying reasons, and outlines current research efforts aimed at bridging the gap between theoretical advancements and clinical applications. Although personalized medicine and phenotypic categorization present promising directions, this review emphasizes the importance of understanding the complex pathogenesis of sepsis and developing targeted, effective therapies to enhance patient outcomes. By addressing the multifaceted nature of sepsis, future research can pave the way for more precise and individualized treatment strategies, ultimately improving the management and prognosis of sepsis patients.

Bisphosphonium Benzene Diimides.

The incorporation of cationic groups onto electron-poor compounds is a viable strategy for achieving potent electron acceptors, as evidenced by reports of air-stable radical forms of large aromatic diimides such as naphthalene and perylene diimides. These ions have also been observed to exhibit anion-π interaction tendencies of interest in molecular recognition applications. The benefits of phosphonium incorporation, however, have not yet been extended to the smallest benzene diimides. Here, we report that dibrominated pyromellitic diimide and mellophanic diimide both readily undergo substitution reactions with phosphine sources to yield bisphosphonium compounds. In the single crystalline form, these dications display anion-π interactions and, in the case of mellophanic diimide, the stabilization of a bromide-water H-bonding ring pattern. The reaction of these dications with chemical reductants readily provides the singly and doubly reduced redox states, which were characterized by UV-vis spectroscopy and found to exhibit intense absorptions extending into the near-IR region. Taken together, this work demonstrates that phosphonium incorporation onto congested aromatic diimide scaffolds is synthetically viable and produces unusual electron-poor compounds.

Enhancing Identification of High-Risk cN0 Lung Adenocarcinoma Patients Using MRI-Based Radiomic Features.

Purpose: To develop an MRI-based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space (STAS), and poorly differentiated patterns. Materials and Methods: As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, SUVmax (maximum standardized uptake value) on FDG PET/CT, and the mean ADC value on DWI, were considered together to build prediction models for high-risk pathologic features. Results: Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The MR-eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p<0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p<0.001), worse 4-year disease free survival (p<0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC 0.860 and 0.907, respectively). Conclusion: Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.

Discrete prognostic implication of sarcopenia according to nutritional status in surgically treated patients with hypopharyngeal cancer.

BACKGROUND: Nutritional status and sarcopenia affects the prognosis of head and neck cancers including hypopharyngeal cancer. Hypopharyngeal cancer patients tend to exhibit sarcopenia, which is associated with poor treatment outcomes. This study aims to determine the correlation between nutritional status and sarcopenia, and their prognostic role in surgically treated hypopharyngeal cancer. MATERIALS AND METHODS: Patients who had been diagnosed with squamous cell carcinoma originating from the hypopharynx and underwent surgery between January 2009 and December 2019 were enrolled in this study. The median neutrophil-to-lymphocyte ratio and prognostic nutritional index (PNI) of the cohort were considered the cut-off values. Sarcopenia was evaluated by measuring skeletal muscle index (SMI) at the third lumbar vertebra. Clinical and serological factors predictive of survival outcomes were evaluated. RESULTS: Patients with high PNI showed better 5-year Overall survival (OS) (52.8% vs. 27.2%, p = 0.001) and disease-free survival (DFS) (59.6% vs. 44.6%, p = 0.033) than those with low PNI. Likewise, patients with low SMI showed worse 5-year OS (25.0% vs. 60.9%, p = 0.002) and DFS (42.4% vs. 68.7%, p = 0.034) than patients with high SMI. Among the patients with high PNI, those with sarcopenia displayed significantly worse OS than those with high SMI (78.0% vs. 34.4%, p = 0.049). High PNI with high SMI presented better overall (p = 0.010) and DFS (p = 0.055) than any other group. CONCLUSIONS: Both sarcopenia and PNI were associated with the prognosis of hypopharyngeal cancer. Considering that PNI and sarcopenia indicate the nutritional status, nutritional status may be a significant risk factor. Therefore, nutritional support that ameliorates sarcopenia may improve survival outcomes in surgically treated patients with hypopharyngeal cancer.

Platelet-Rich Plasma-Embedded Porous Polycaprolactone Film with a Large Surface Area for Effective Hemostasis.

BACKGROUND: Uncontrollable and widespread bleeding caused by surgery or sudden accidents can lead to death if not treated with appropriate hemostasis. To prevent excessive life-threatening bleeding, various hemostatic agents based on polymeric biomaterials with various additives for accelerated blood coagulation have been adopted in clinical fields. In particular, platelet-rich plasma (PRP), which contains many blood coagulation factors that can accelerate blood clot formation, is considered as one of the most effective hemostatic additives. METHODS: We investigated a PRP-embedded porous film using discarded (expired) PRP and a film with a leaf-stacked structure (FLSS), as a hemostatic agent to induce rapid hemostasis. The film, which contained an LSS on one side (PCL-FLSS), was fabricated by a simple heating-cooling technique using tetraglycol and polycaprolactone (PCL) film. Activated PRP was obtained by the thawing of frozen PRP at the end of its expiration date (the platelet cell membrane is disrupted during the freezing and thawing of PRP, thus releasing various coagulation factors) and embedded in the PCL-FLSS (PRP-FLSS). RESULTS: From in vitro and in vivo experiments using a rat hepatic bleeding model, it was recognized that PRP-FLSS is not only biocompatible but also significantly accelerates blood clotting and thus prevents rapid bleeding, probably due to a synergistic effect of the sufficient supply of various blood coagulants from activated PRP embedded in the LSS layer and the large surface area of the LSS itself. CONCLUSION: The study suggests that PRP-FLSS, a combination of a porous polymer matrix with a unique morphology and discarded biofunctional resources, can be an advanced hemostatic agent as well as an upcycling platform to avoid the waste of biofunctional resources.

Effect of Rumen-Protected L-Tryptophan or L-Ascorbic Acid on Plasma Metabolites and Milk Production Characteristics of Lactating Holstein Cows during Summer Conditions.

This study investigated the effects of rumen-protected L-tryptophan or L-ascorbic acid supplementation on the productivity of lactating Holstein cows during a high-temperature period. Thirty cows were assigned to three dietary groups: control (CON), treatment 1 (TRT 1; rumen-protected L-tryptophan, 20 g/cow/d), and treatment 2 (TRT 2; rumen-protected L-ascorbic acid, 20 g/cow/d). As the high-temperature period progressed, the decrease in milk yield and dry matter intake (DMI) in the TRT 1 and TRT 2 groups was lower than that in the CON group. The total protein level in the plasma of the TRT 1 group was higher than that in the CON group (p < 0.05). Milk melatonin concentration was higher in the TRT 1 group than in the CON and TRT 2 groups (p < 0.05). Thus, the present results indicate that rumen-protected L-tryptophan or L-ascorbic acid has positive effects in preventing declines in DMI and milk yield by reducing heat stress in Holstein cows. In particular, rumen-protected L-tryptophan is considered effective in increasing the melatonin concentration in milk.

Emergency medicine residents' learning curve in diagnosing deep vein thrombosis with 3-point venous point-of-care ultrasound.

BACKGROUND: Many cases of deep vein thrombosis (DVT) are diagnosed in the emergency department, and abbreviated lower extremity venous point-of-care ultrasound (POCUS) has already shown an accuracy comparable to that of specialists. This study aimed to identify the learning curve necessary for emergency medicine (EM) residents to achieve expertise-level accuracy in diagnosing DVT through a 3-point lower extremity venous POCUS. METHODS: This prospective study was conducted at an emergency department between May 2021 and October 2022. Four EM residents underwent a one-hour POCUS training session and performed DVT assessments in participants with DVT symptoms or confirmed pulmonary embolism. POCUS was performed at three proximal lower extremity sites to evaluate the thrombi presence and vein compressibility, with results validated by specialized radiology ultrasound. Cumulative sum (CUSUM) and the Bush and Mosteller models were used to analyze the learning curve, while generalized estimating equations were used to identify factors affecting diagnostic accuracy. RESULTS: 91 POCUS scans were conducted in 49 patients, resulting in 22% DVT confirmed by specialized venous ultrasound. In the CUSUM analysis, all four EM residents attained a 90% success rate at the common femoral vein, whereas only half achieved this rate when all three sites were considered. According to Bush and Mosteller models, 13-18 cases are required to attain 90-95% diagnostic accuracy. After 10-16 cases, the examination time for each resident decreased, and a 20% increase in examiner confidence was linked to a 2.506-fold increase in the DVT diagnosis accuracy. CONCLUSION: EM residents generally required 13-18 cases for 90-95% DVT diagnostic accuracy, but proficiency varied among individuals, particularly requiring more cases for regions outside the common femoral vein.

Effect of virtual reality-based biofeedback for depressive and anxiety symptoms: Randomized controlled study.

BACKGROUND: The use of virtual reality (VR)-based biofeedback (BF), a relatively new intervention, is a non-pharmacological treatment of depressive and anxiety symptoms. However, studies on VR-based BF are lacking and inconclusive. METHODS: A total of 131 adults were recruited from the community. Participants who scored ≥10 on the Patient Health Questionnaire-9 (PHQ-9) or ≥9 on the Panic Disorder Severity Scale (PDSS) were included in the group with depressive or anxiety symptoms (DAS group), and others as the healthy control group (HC group). Participants from the DAS group were randomly assigned to VR-based or conventional BF intervention. All individuals visited at three times (weeks 0, 2, and 4), and completed the Montgomery-Asberg Depression Rating Scale (MADRS), the State-Trait Anxiety Inventory (STAI), and a visual analog scale (VAS) before and after the intervention, and PHQ-9 at the beginning and final visit. RESULTS: The analysis included a total of 118 participants (DAS/VR: 40, DAS/BF: 38, HC/VR: 40). There was no significant difference in demographic variables among the three groups. After the intervention, the DAS/VR group exhibited significant decreases in MADRS (70.0 %), PHQ-9 (64.1 %), STAI (29.5 %), and VAS (61.7 %) scores compared to the baseline (p <0.001). There were no significant differences between the effects of VR-based BF and conventional BF with a therapist. The HC group also showed significant decreases in the measures of depression and anxiety after receiving VR-based BF. CONCLUSION: VR-based BF was effective in reducing depressive and anxiety symptoms, even for subthreshold depression and anxiety symptoms in the HC group.

Anti-chitinase-3-like 1 antibody attenuated atopic dermatitis-like skin inflammation through inhibition of STAT3-dependent CXCL8 expression.

BACKGROUND AND PURPOSE: Chitinase-3-like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti-CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action. EXPERIMENTAL APPROACH: The effect of CHI3L1 antibody on phthalic anhydride-induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis-related cytokines were determined using an enzyme-linked immunosorbent assay, and RT-qPCR, STAT3 and CXCL8 signalling were measured by western blotting. KEY RESULTS: Anti-CHI3L1 antibody suppressed phthalic anhydride-induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride-induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride-treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis-related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL-4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein-association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL-1ß, IL-4, CXCL8, TSLP, and the expression of CHI3L1 and p-STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p-STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model. CONCLUSION AND IMPLICATIONS: Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis.

Resting energy expenditure differs among individuals with different levels of perceived thermal sensitivity: A cross-sectional study.

Metabolic rate has been used in thermophysiological models for predicting the thermal response of humans. However, only a few studies have investigated the association between an individual's trait-like thermal sensitivity and resting energy expenditure (REE), which resulted in inconsistent results. This study aimed to explore the association between REE and perceived thermal sensitivity. The REE of healthy adults was measured using an indirect calorimeter, and perceived thermal intolerance and sensation in the body were evaluated using a self-administered questionnaire. In total, 1567 individuals were included in the analysis (women = 68.9%, age = 41.1 ±â€…13.2 years, body mass index = 23.3 ±â€…3.3 kg/m2, REE = 1532.1 ±â€…362.4 kcal/d). More women had high cold intolerance (31.8%) than men (12.7%), and more men had high heat intolerance (23.6%) than women (16.1%). In contrast, more women experienced both cold (53.8%) and heat (40.6%) sensations in the body than men (cold, 29.1%; heat, 27.9%). After adjusting for age, fat-free mass, and fat mass, lower cold intolerance, higher heat intolerance, and heat sensation were associated with increased REE only in men (cold intolerance, P for trend = .001; heat intolerance, P for trend = .037; heat sensation, P = .046), whereas cold sensation was associated with decreased REE only in women (P = .023). These findings suggest a link between the perceived thermal sensitivity and REE levels in healthy individuals.

Efficacy and Safety of WCFA19 (Weissella confusa WIKIM51) in Reducing Body Fat in Overweight and Obese Adults.

Background: WCFA19 (Weissella confusa WIKIM51), found during the fermentation of kimchi, is known for its inhibitory effects on body weight and body fat. This study looked at the impact of WCFA19 isolated from dandelion kimchi on weight loss in overweight and obese adults that are otherwise healthy. Methods: This study was conducted as a multicenter, double-blind, randomized, placebo-controlled study with 104 overweight and obese subjects. Subjects were randomized evenly into the test group (WCFA19, 500 mg, n = 40) or control group (n = 34) for 12 weeks from 14 June 2021 to 24 December 2021. Effects were based on DEXA to measure changes in body fat mass and percentage. Results: Among the 74 subjects analyzed, WCFA19 oral supplementation for 12 weeks resulted in a significant decrease in body fat mass of 633.38 ± 1396.17 g (p = 0.0066) in overweight and obese individuals in the experimental group. The control group showed an increase of 59.10 ± 1120.57 g (p = 0.7604), indicating a statistically significant difference between the two groups. There was also a statistically significant difference (p = 0.0448) in the change in body fat percentage, with a decrease of 0.41 ± 1.22% (p = 0.0424) in the experimental group and an increase of 0.17 ± 1.21% (p = 0.4078) in the control group. No significant adverse events were reported. Conclusions: Oral supplementation of 500 mg of WCFA19 for 12 weeks is associated with a decrease in body weight, particularly in body fat mass and percentage.

Synthesis, Antiproliferative Activity and Molecular Docking Analysis of Both Enantiomerically Pure Decursin Derivatives as Anticancer Agents.

Using (S)-decursinol isolated from root of Angelica gigas Nakai (AGN), we semi-synthesized and evaluated a series of both enantiomerically pure decursin derivatives for their antiproliferative activities against A549 human lung cancer cells. All synthesized compounds showed a broad spectrum of inhibitory activities against the growth of A549 cells. Especially, compound (S)-2d with (E)-(furan-3-yl)acryloyl group showed the most potent activity (IC50: 14.03 µM) against A549 cancer cells as compared with the reference compound, decursin (IC50: 43.55 µM) and its enantiomer, (R)-2d (IC50: 151.59 µM). Western blotting assays indicated that (S)-2d more strongly inhibited Janus kinase 1 (JAK1) and signal transducer and activator of transcription activation 3 (STAT3) phosphorylation than decursin in a dose-dependent manner, while having no effect on CXCR7 overexpression and total STAT3 level. In addition, (S)-2d induced cell cycle arrest at G1 phase and subsequent apoptotic cell death in A549 cancer cells. Our combined analysis of molecular docking studies and biological data suggests that the inhibition of JAK1 with (S)-2d resulted in loss of STAT3 phosphorylation and inhibition of cell growth in A549 cancer cells. These overall results strongly suggest that (S)-2d (MRC-D-004) as a novel JAK1 inhibitor may have therapeutic potential in the treatment of A549 human lung cancers by targeting the JAK1/STAT3 signaling pathway.

Mechanism of Z-Selective Allylic Functionalization via Thianthrenium Salts.

A detailed mechanistic study of the Z-selective allylic functionalization via thianthrenium salts is presented. Kinetic analyses, deuterium labeling experiments, and computational methods are used to rationalize the observed reactivity and selectivity. We find that the reaction proceeds via a rate-determining and stereodetermining allylic deprotonation of an alkenylthianthrenium species. The Z-configuration of the resultant allylic ylide is translated into the Z-allylic amine product through a sequence of subsequent fast and irreversible steps: protonation to form a Z-allylic thianthrenium electrophile and then regioselective substitution by the nucleophile. In the stereodetermining deprotonation step, computational studies identified a series of stabilizing nonbonding interactions in the Z-alkene-forming transition state that contribute to the stereoselectivity.

Modeling of solar UV-induced photodamage on the hair follicles in human skin organoids.

Solar ultraviolet (sUV) exposure is known to cause skin damage. However, the pathological mechanisms of sUV on hair follicles have not been extensively explored. Here, we established a model of sUV-exposed skin and its appendages using human induced pluripotent stem cell-derived skin organoids with planar morphology containing hair follicles. Our model closely recapitulated several symptoms of photodamage, including skin barrier disruption, extracellular matrix degradation, and inflammatory response. Specifically, sUV induced structural damage and catagenic transition in hair follicles. As a potential therapeutic agent for hair follicles, we applied exosomes isolated from human umbilical cord blood-derived mesenchymal stem cells to sUV-exposed organoids. As a result, exosomes effectively alleviated inflammatory responses by inhibiting NF-κB activation, thereby suppressing structural damage and promoting hair follicle regeneration. Ultimately, our model provided a valuable platform to mimic skin diseases, particularly those involving hair follicles, and to evaluate the efficacy and underlying mechanisms of potential therapeutics.

A novel zwitterion incorporated Nano-crystalline ceramic and polymer for bacterial resistant dental CAD-CAM block.

OBJECTIVES: To create bacteria-resistant dental CAD-CAM blocks with a biofilm-resistant effect by incorporating Nano-crystalline ceramic and polymer (NCP) with 2-methacryloyloxyethyl phosphorylcholine (MPC) and sulfobetaine methacrylate (SBMA) and at an equimolar ratio, referred to as MS. METHODS: Experimental groups comprised NCP blocks containing zwitterions at 0.15wt% (MS015) and 0.45wt% (MS045). NCP blocks without MS served as control (CTRL). Flexural strength, surface hardness, water sorption and solubility, photometric properties, and cytotoxicity were assessed for all samples. Additionally, the resistance to single and multi-species bacterial adhesion was investigated. RESULTS: MS045 showed significant reduction in flexural strength (P < 0.01) compared to both CTRL and MS015. Both MS015 and MS045 showed significantly increased water sorption and significant reduction in water solubility compared to CTRL. Light transmission remained consistent across all MS content levels, but the irradiance value decreased by 12 % in the MS045 group compared to the MS015 group. Notably, compared to the CTRL group, the MS015 group exhibited enhanced resistance to adhesion by Porphyromonas gingivalis and a multi-species salivary biofilm, with biofilm thickness and biomass reduced by 45 % and 56 %, respectively. CONCLUSIONS: NCP containing 0.15 % MS can effectively reduce adhesion of multiple species of bacteria while maintaining physical and mechanical properties. CLINICAL SIGNIFICANCE: NCP integrating zwitterions is clinically advantageous in resisting bacterial adhesion at internal and external margins of milled indirect restoration.