Recombinant Human IL-32θ Induces Polarization Into M1-like Macrophage in Human Monocytic Cells.

The tumor microenvironment (TME) is formed by several immune cells. Notably, tumor-associated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32θ was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) was generated using an Escherichia coli expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32θ. The mRNA level of M1 macrophage markers (IL-1ß, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFß, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.

Dual Antibacterial Properties of Copper-Coated Nanotextured Stainless Steel.

Bacterial adhesion to stainless steel, an alloy commonly used in shared settings, numerous medical devices, and food and beverage sectors, can give rise to serious infections, ultimately leading to morbidity, mortality, and significant healthcare expenses. In this study, Cu-coated nanotextured stainless steel (nSS) fabrication have been demonstrated using electrochemical technique and its potential as an antibiotic-free biocidal surface against Gram-positive and negative bacteria. As nanotexture and Cu combine for dual methods of killing, this material should not contribute to drug-resistant bacteria as antibiotic use does. This approach involves applying a Cu coating on nanotextured stainless steel, resulting in an antibacterial activity within 30 min. Comprehensive characterization of the surface revealing that the Cu coating consists of metallic Cu and oxidized states (Cu2+ and Cu+), has been performed by this study. Cu-coated nSS induces a remarkable reduction of 97% in Gram-negative Escherichia coli and 99% Gram-positive Staphylococcus epidermidis bacteria. This material has potential to be used to create effective, scalable, and sustainable solutions to prevent bacterial infections caused by surface contamination without contributing to antibiotic resistance.

Synovial fluid monocyte-to-lymphocyte ratio in knee osteoarthritis patients predicts patient response to conservative treatment: a retrospective cohort study.

BACKGROUND: Biomarkers that predict the treatment response in patients with knee osteoarthritis are scarce. This study aimed to investigate the potential role of synovial fluid cell counts and their ratios as biomarkers of primary knee osteoarthritis. METHODS: This retrospective study investigated 96 consecutive knee osteoarthritis patients with knee effusion who underwent joint fluid aspiration analysis and received concomitant intra-articular corticosteroid injections and blood tests. The monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) were calculated. After 6 months of treatment, patients were divided into two groups: the responder group showing symptom resolution, defined by a visual analog scale (VAS) score of ≤ 3, without additional treatment, and the non-responder group showing residual symptoms, defined by a VAS score of > 3 and requiring further intervention, such as additional medication, repeated injections, or surgical treatment. Unpaired t-tests and univariate and multivariate logistic regression analyses were conducted between the two groups to predict treatment response after conservative treatment. The predictive value was calculated using the area under the receiver operating characteristic curve, and the optimal cutoff value was determined. RESULTS: Synovial fluid MLR was significantly higher in the non-responder group compared to the responder group (1.86 ± 1.64 vs. 1.11 ± 1.37, respectively; p = 0.02). After accounting for confounding variables, odds ratio of non-responder due to increased MLR were 1.63 (95% confidence interval: 1.11-2.39). The optimal MLR cutoff value for predicting patient response to conservative treatment was 0.941. CONCLUSIONS: MLR may be a potential biomarker for predicting the response to conservative treatment in patients with primary knee osteoarthritis.

Asbestos Exposure and Ovarian Cancer: A Meta-analysis.

Background: The International Agency for Research on Cancer (IARC) Monograph conducted a systematic review of the relationship between asbestos and ovarian cancer. However, there may have been information bias due to the undue weight given to few articles. To address this limitation, the present study performed a meta-analysis integrating studies published both before and after the 2012 IARC Monograph on Asbestos, with the aim of investigating the association between asbestos exposure and ovarian cancer. Methods: A comprehensive search of major journal databases was conducted to identify studies examining the relationship between asbestos exposure and ovarian cancer, including those featured in the 2012 IARC Monograph on Asbestos. A meta-analysis on asbestos exposure and cancer risk was performed. Results: The meta-analysis of studies published after the 2012 IARC Monograph on Asbestos found a summary Standardized Mortality Ratio (SMR) of 2.04 (95% CI: 1.03-4.05; p = 0.0123; 5 studies), with a significant degree of heterogeneity among the studies (I2 = 72.99%). The combined analysis of 15 studies before and after the 2012 IARC Monograph showed an overall summary SMR of 1.72 (95% CI: 1.43-2.06; p = 0.0349; 15 studies), with a moderate degree of heterogeneity (I2 = 42.99%). Conclusion: This meta-analysis provides evidence of a significant association between asbestos exposure and ovarian cancer mortality. While the possibility of misdiagnosis in earlier studies cannot be completely ruled out, recent findings suggest a robust correlation between asbestos exposure and ovarian cancer. This highlights the importance of sustained efforts to minimize asbestos exposure and protect public health.

Clinical and radiological results of high tibial of osteotomy over the age of 65 are comparable to that of under 55 at minimum 2-year follow-up: a propensity score matched analysis.

PURPOSE: The results of medial open-wedge high tibial osteotomy (MOWHTO) according to age is inconclusive. This study aimed to compare the clinical outcomes and failure of MOWHTO in patients < 55 years and > 65 years. METHODS: Consecutive patients who underwent MOWHTO from July 2009 to August 2020 were retrospectively analyzed. 205 patients were considered for analysis. A 1-to-1 propensity score matched analysis to assess clinical outcomes scores including International Knee Documentation Committee (IKDC) subjective score and Lysholm score, radiologic outcomes, complication, and Total Knee Arthroplasty (TKA) conversion between patients > 65 years and patients < 55 years was performed. Radiologic outcomes included Hip-Knee-Ankle (HKA) angle, Weight Bearing Line ratio (WBLR), posterior tibial slope (PTS), and Insall-Salvati (IS) ratio before and after surgery. RESULTS: The follow-up period was 50.4 months in patients > 65 years and 55.3 months in patients < 55 years. There was no significant difference in the preoperative and postoperative HKA angle, WBLR, PTS, IS ratio, IKDC score and Lysholm score between the two groups. The arthroscopic evaluation of cartilage did not show any statistically significant differences between the two groups. Regarding Minimal clinically important differences (MCID), in the 26% of the older group exceeded MCID of IKDC score; 45% of the older group exceeded MCID of Lysholm score. In the younger group, 24% exceeded MCID of IKDC score and 35% exceeded MCID of Lysholm score. In older group, there were 7 (11.3%) cases of TKA conversion while no TKA conversion was recorded in the younger group. (P = 0.007) The average time to TKA conversion was 67 months. (42 months to 90 months) Kaplan-Meier analysis revealed that the survival rate was 95.2% at 4 years in the older group. CONCLUSION: Similar clinical results were obtained in patients over 65 years of age that were eligible for MOWHTO at minimum 2-year follow-up as in patients under 55 years of age. MOWHTO may be a viable option in older patients if proper indications are met. However, the risk of TKA conversion must be considered preoperatively and discussed with patients. STUDY DESIGN: Cohort study; Level of evidence, 3.

Costal Chondrocyte-Derived Pellet-Type Autologous Chondrocyte Implantation Versus Microfracture for the Treatment of Articular Cartilage Defects: A 5-Year Follow-up of a Prospective Randomized Trial.

BACKGROUND: Costal chondrocyte-derived pellet-type autologous chondrocyte implantation (CCP-ACI) has been introduced as a new therapeutic option for the treatment of articular cartilage defects. We had previously conducted a randomized controlled trial comparing CCP-ACI versus microfracture at 1 year postoperatively. PURPOSE: To compare the efficacy and safety of CCP-ACI versus microfracture for the treatment of articular cartilage defects of the knee at 5 years postoperatively. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: This study describes the mean 5-year follow-up of a previously published prospective clinical trial. The previous prospective trial compared the results of CCP-ACI versus microfracture until 1 year of follow-up. Of the 30 patients who were included in the previous study, 25 were followed up for 5 years. Patients were evaluated based on clinical outcome scores (Lysholm score, International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score [KOOS], and visual analog scale for pain), magnetic resonance imaging findings, and rates of treatment failure at last follow-up. RESULTS: The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score in the CCP-ACI group was significantly higher than that in the microfracture group at 5 years (62.3 vs 26.7, respectively; P < .0001). The Lysholm score and KOOS score in the CCP-ACI group were significantly higher than those in the microfracture group at 5 years (84.5 vs 64.9, respectively, and 390.9 vs 303.0, respectively; P = .023 and P = .017, respectively). There was 1 case of treatment failure that occurred in the microfracture group. CONCLUSION: The present randomized controlled trial indicated that the results of both procedures clinically and statistically significantly improved at 1 and 5 years' follow-up in treating cartilage defects, but the results of CCP-ACI were superior to those of microfracture. Magnetic resonance imaging conducted at 1 year and 5 years after CCP-ACI revealed statistically significant superior structural integration with native cartilage tissue compared with microfracture. REGISTRATION: NCT03545269 (ClinicalTrials.gov).

Controlled posterior condylar milling technique for unicompartmental knee arthroplasty minimises tibia resection during gap balancing: Short-term clinical results.

PURPOSE: The purpose of this study was to demonstrate the clinical utility of controlled posterior condylar milling (CPCM) in gap balancing while minimally resecting the tibia during fixed-bearing unicompartmental knee arthroplasty (UKA). METHODS: This study is a retrospective cohort study. Patients who underwent medial UKA for isolated medial compartment osteoarthritis with a minimum follow-up of 2 years were included. The patients were divided into two groups: the conventional group (n = 56) and the CPCM group (n = 66). In the CPCM group, the proximal tibia was resected at the level of the distal end of the subchondral bone. If the flexion gap was tighter than extension, the posterior condyle was additionally milled to adjust gap tightness. Standing knee X-ray and scanogram were used to evaluate alignment and tibia resection amount. Range of motion (ROM) and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scores were used to evaluate clinical outcomes. RESULTS: The CPCM group showed significantly smaller tibia resection (3.6 ± 1.9 mm) compared to the conventional group (5.2 ± 2.7 mm) (p < 0.001). Postoperative ROM (133.0 ± 8.3°, 135.2 ± 7.2°, n.s.) and WOMAC (19.3 ± 13.6, 23.6 ± 17.7, n.s.) were not significantly different between the two groups. Postoperative periprosthetic fractures occurred in two patients in conventional group, while the CPCM group had no periprosthetic fractures. CONCLUSION: The CPCM technique may be a simple and useful intraoperative technique that can achieve minimal tibia resection and promising clinical outcomes while easily adjusting gap tightness between flexion and extension during medial fixed-bearing UKA. LEVEL OF EVIDENCE: Level III.

Machine Learning-Based Predictive Models for 90-Day Readmission of Total Joint Arthroplasty Using Comprehensive Electronic Health Records and Patient-Reported Outcome Measures.

Background: The Centers for Medicare & Medicaid Services currently incentivizes hospitals to reduce postdischarge adverse events such as unplanned hospital readmissions for patients who underwent total joint arthroplasty (TJA). This study aimed to predict 90-day TJA readmissions from our comprehensive electronic health record data and routinely collected patient-reported outcome measures. Methods: We retrospectively queried all TJA-related readmissions in our tertiary care center between 2016 and 2019. A total of 104-episode care characteristics and preoperative patient-reported outcome measures were used to develop several machine learning models for prediction performance evaluation and comparison. For interpretability, a logistic regression model was built to investigate the statistical significance, magnitudes, and directions of associations between risk factors and readmission. Results: Given the significant imbalanced outcome (5.8% of patients were readmitted), our models robustly predicted the outcome, yielding areas under the receiver operating characteristic curves over 0.8, recalls over 0.5, and precisions over 0.5. In addition, the logistic regression model identified risk factors predicting readmission: diabetes, preadmission medication prescriptions (ie, nonsteroidal anti-inflammatory drug, corticosteroid, and narcotic), discharge to a skilled nursing facility, and postdischarge care behaviors within 90 days. Notably, low self-reported confidence to carry out social activities accurately predicted readmission. Conclusions: A machine learning model can help identify patients who are at substantially increased risk of a readmission after TJA. This finding may allow for health-care providers to increase resources targeting these patients. In addition, a poor response to the "social activities" question may be a useful indicator that predicts a significant increased risk of readmission after TJA.

Modulatory effects of point-mutated IL-32θ (A94V) on tumor progression in triple-negative breast cancer cells.

Breast cancer is a frequently diagnosed cancer and the leading cause of death among women worldwide. Tumor-associated macrophages stimulate cytokines and chemokines, which induce angiogenesis, metastasis, proliferation, and tumor-infiltrating immune cells. Although interleukin-32 (IL-32) has been implicated in the development and modulation of several cancers, its function in breast cancer remains elusive. Mutation of interleukin-32θ (IL-32θ) in the tissues of patients with breast cancer was detected by Sanger sequencing. RT-qPCR was used to detect the mRNA levels of inflammatory cytokines, chemokines, and mediators. The secreted proteins were detected using respective enzyme-linked immunosorbent assays. Evaluation of the inhibitory effect of mutant IL-32θ on proliferation, migration, epithelial-mesenchymal transition (EMT), and cell cycle arrest in breast cancer cells was conducted using MTS assays, migration assays, and Western blotting. A point mutation (281C>T, Ala94Val) was detected in IL-32θ in both breast tumors and adjacent normal tissues, which suppressed the expression of pro-inflammatory factors, EMT factors, and cell cycle related factors. Mutated IL-32θ inhibited the expression of inflammatory factors by regulating the NF-κB pathway. Furthermore, mutated IL-32θ suppressed EMT markers and cell cycle related factors through the FAK/PI3K/AKT pathway. It was inferred that mutated IL-32θ modulates breast cancer progression. Mutated IL-32θ (A94V) inhibited inflammation, EMT, and proliferation in breast cancer by regulating the NF-κB (p65/p50) and FAK-PI3K-GSK3 pathways.

Fixed-Bearing Unicompartmental Knee Arthroplasty in Tibia Vara Knees Results in Joint Surface Malalignment and Varus Joint Line Obliquity, but Does Not Affect Functional Outcomes at Greater Than 5 Years Follow-Up.

BACKGROUND: This study aimed to investigate the clinical outcomes of fixed-bearing medial unicompartmental knee arthroplasty (UKA) for tibia vara knees and the associated changes in joint space malalignment (JSM) and joint line obliquity (JLO). METHODS: We retrospectively analyzed a consecutive group of 100 patients who underwent fixed-bearing medial UKA with a preoperative medial proximal tibia angle (MPTA) ≥86° (n = 50) and MPTA <86° (n = 50) and who had a minimum 5-year follow-up. Radiological parameters, including the hip-knee-ankle angle, MPTA, and the postoperative JSM and JLO, were measured. Functional evaluation was performed using the range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index score. RESULTS: The MPTA <86° group showed significantly higher postoperative JLO (91.8 versus 90.4°, respectively; P = .002) and JSM (6.1 versus 4.2°, respectively; P = .026) compared to the MPTA ≥86° group. Functional outcomes, including range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index scores, were not significantly different between the 2 groups. CONCLUSIONS: Fixed-bearing medial UKA is a safe and effective surgical option for patients who have tibia vara knees, as an increase in JLO and JSM postoperatively does not have a clinically relevant impact, even after a minimum 5-year follow-up.

Synovium-Derived Mesenchymal Stem Cell-Based Scaffold-Free Fibrocartilage Engineering for Bone-Tendon Interface Healing in an Anterior Cruciate Ligament Reconstruction Model.

BACKGROUND: Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone-tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model. METHODS: Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including  TGF-ß-only, CTGF-only, and TGF-ß + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model. RESULTS: Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-ß and CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period. CONCLUSION: Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.

The Effect of Aging on Outcomes after Posterior Cruciate Ligament Reconstruction: Older (≥ 50 Years) Versus Younger (< 50 Years) Patients.

Background: This study aimed to evaluate the clinical and radiological outcomes after posterior cruciate ligament (PCL) reconstruction in ≥ 50-year-old patients. Methods: This retrospective case-control study reviewed 28 patients (age, ≥ 50 years) who underwent PCL reconstruction from 2004 to 2018. These patients were 1 : 1 matched to < 50-year-old patients by sex. Clinical, radiological, and survivorship outcomes of the patients were assessed at the final follow-up. Failure of PCL reconstruction was defined as the requirement for additional surgery (revision PCL reconstruction, high tibial osteotomy, or arthroplasty) due to unrelieved symptoms or grade III instability on stress radiographs. Results: The mean follow-up periods (± standard deviation) in < 50- and ≥ 50-year-old patients were 3.9 ± 1.0 years and 3.6 ± 1.9 years, respectively (p = 0.583). In < 50- and ≥ 50-year-old patients, the mean International Knee Documentation Committee scores were 64.1 ± 10.3 and 53.5 ± 17.3; mean Lysholm scores were 81.4 ± 13.0 and 66.3 ± 21.5; and mean Tegner activity scores were 6.1 ± 1.4 and 4.8 ± 1.7, respectively (p = 0.032, p = 0.018, and p = 0.016, respectively). Side-to-side differences in posterior translation on Telos stress radiographs at the final follow-up were 4.4 ± 1.4 mm and 6.9 ± 3.0 mm in < 50- and ≥ 50-year-old patients, respectively (p < 0.001). According to Kaplan-Meier analysis, the failure-free survival rates of both groups were significantly different in the follow-up period (p = 0.014). The failure-free survival rates for < 50- and ≥ 50-year-old patients were 100% and 78.6%, respectively. Conclusions: Clinical, radiological, and survivorship outcomes were inferior among ≥ 50-year-old patients after PCL reconstruction. Thus, surgeons should be careful when deciding and performing PCL reconstruction in patients 50 years old or over.

Development of Self-Assembled Protein Nanocage Spatially Functionalized with HA Stalk as a Broadly Cross-Reactive Influenza Vaccine Platform.

There remains a need for the development of a universal influenza vaccine, as current seasonal influenza vaccines exhibit limited protection against mismatched, mutated, or pandemic influenza viruses. A desirable approach to developing an effective universal influenza vaccine is the incorporation of highly conserved antigens in a multivalent scaffold that enhances their immunogenicity. Here, we develop a broadly cross-reactive influenza vaccine by functionalizing self-assembled protein nanocages (SAPNs) with multiple copies of the hemagglutinin stalk on the outer surface and matrix protein 2 ectodomain on the inner surface. SAPNs were generated by engineering short coiled coils, and the design was simulated by MD GROMACS. Due to the short sequences, off-target immune responses against empty SAPN scaffolds were not seen in immunized mice. Vaccination with the multivalent SAPNs induces high levels of broadly cross-reactive antibodies of only external antigens, demonstrating tight spatial control over the designed antigen placement. This work demonstrates the use of SAPNs as a potential influenza vaccine.

Dual-Antigen Subunit Vaccine Nanoparticles for Scrub Typhus.

Orientia tsutsugamushi is the causative pathogen of scrub typhus, an acute febrile disease prevalent in the Asia-Pacific region that is spread to people through chigger bites. Despite the emerging threat, there is no currently available vaccine against O. tsutsugamushi. Here, we developed dual-antigen subunit vaccine nanoparticles using recombinant 47 kD and 56 kD proteins, which are immunogenic outer membrane antigens of O. tsutsugamushi. The biocompatible protein vaccine nanoparticles were formed via desolvation of r56 or r47E antigens with acetone, coating with an additional layer of the 56 kD protein, and stabilization with reducible homobifunctional DTSSP and heterobifunctional SDAD crosslinkers. The dual-antigen subunit vaccine nanoparticles significantly improved antigen-specific antibody responses in vaccinated mice. Most importantly, the dual-antigen nanoparticles coated with an additional layer of the 56 kD protein were markedly more immunogenic than soluble antigens or single-antigen nanoparticles in the context of cellular immune responses. Given the significance of cellular immune responses for protection against O. tsutsugamushi, these results demonstrate the potent immunogenicity of dual-layered antigen nanoparticles and their potential as a promising strategy for developing vaccines against scrub typhus.

MMPP is a novel VEGFR2 inhibitor that suppresses angiogenesis via VEGFR2/AKT/ERK/NF-κB pathway.

Many types of cancer are associated with excessive angiogenesis. Anti-angiogenic treatment is an effective strategy for treating solid cancers. This study aimed to demonstrate the inhibitory effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) in VEGFA-induced angiogenesis. The results indicated that MMPP effectively suppressed various angiogenic processes, such as cell migration, invasion, tube formation, and sprouting of new vessels in human umbilical vein endothelial cells (HUVECs) and mouse aortic ring. The inhibitory mechanism of MMPP on angiogenesis involves targeting VEGFR2. MMPP showed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stability and inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-κB, and it downregulated NF-κB target genes such as VEGFA, VEGFR2, MMP2, and MMP9. Furthermore, conditioned medium from MMPP-treated breast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promise as a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/NF-κB signaling pathway.

Development of algorithm for work intensity evaluation using excess overwork index of construction workers with real-time heart rate measurement device.

Background: The construction workers are vulnerable to fatigue due to high physical workload. This study aimed to investigate the relationship between overwork and heart rate in construction workers and propose a scheme to prevent overwork in advance. Methods: We measured the heart rates of construction workers at a construction site of a residential and commercial complex in Seoul from August to October 2021 and develop an index that monitors overwork in real-time. A total of 66 Korean workers participated in the study, wearing real-time heart rate monitoring equipment. The relative heart rate (RHR) was calculated using the minimum and maximum heart rates, and the maximum acceptable working time (MAWT) was estimated using RHR to calculate the workload. The overwork index (OI) was defined as the cumulative workload evaluated with the MAWT. An appropriate scenario line (PSL) was set as an index that can be compared to the OI to evaluate the degree of overwork in real-time. The excess overwork index (EOI) was evaluated in real-time during work performance using the difference between the OI and the PSL. The EOI value was used to perform receiver operating characteristic (ROC) curve analysis to find the optimal cut-off value for classification of overwork state. Results: Of the 60 participants analyzed, 28 (46.7%) were classified as the overwork group based on their RHR. ROC curve analysis showed that the EOI was a good predictor of overwork, with an area under the curve of 0.824. The optimal cut-off values ranged from 21.8% to 24.0% depending on the method used to determine the cut-off point. Conclusion: The EOI showed promising results as a predictive tool to assess overwork in real-time using heart rate monitoring and calculation through MAWT. Further research is needed to assess physical workload accurately and determine cut-off values across industries.

Retro Diels-Alder-triggered self-assembly of a polymerizable macrocyclic diacetylene.

A new triggered self-assembly method, which utilizes retro Diels-Alder (rDA)-promoted self-assembly of a macrocyclic diacetylene, was developed. The steric bulk present in a Diels-Alder (DA) adduct was released by a thermally promoted rDA reaction, resulting in the generation of a linear diacetylene that readily self-assembles to form a supramolecular polymer. The maleimide-containing blue-colored polydiacetylene, which was generated by UV irradiation, was utilized as a thiol specific colorimetric sensor.

Chemical and biological conjugation strategies for the development of multivalent protein vaccine nanoparticles.

The development of subunit vaccine platforms has been of considerable interest due to their good safety profile and ability to be adapted to new antigens, compared to other vaccine typess. Nevertheless, subunit vaccines often lack sufficient immunogenicity to fully protect against infectious diseases. A wide variety of subunit vaccines have been developed to enhance antigen immunogenicity by increasing antigen multivalency, as well as stability and delivery properties, via presentation of antigens on protein nanoparticles. Increasing multivalency can be an effective approach to provide a potent humoral immune response by more strongly engaging and clustering B cell receptors (BCRs) to induce activation, as well as increased uptake by antigen presenting cells and their subsequent T cell activation. Proper orientation of antigen on protein nanoparticles is also considered a crucial factor for enhanced BCR engagement and subsequent immune responses. Therefore, various strategies have been reported to decorate highly repetitive surfaces of protein nanoparticle scaffolds with multiple copies of antigens, arrange antigens in proper orientation, or combinations thereof. In this review, we describe different chemical bioconjugation methods, approaches for genetic fusion of recombinant antigens, biological affinity tags, and enzymatic conjugation methods to effectively present antigens on the surface of protein nanoparticle vaccine scaffolds.

Selective Extracellular Matrix Guided Mesenchymal Stem Cell Self-Aggregate Engineering for Replication of Meniscal Zonal Tissue Gradient in a Porcine Meniscectomy Model.

Degenerative meniscus tears (DMTs) are prevalent findings in osteoarthritic knees, yet current treatment is mostly limited to arthroscopic partial meniscectomy rather than regeneration, which further exacerbates arthritic changes. Translational research regarding meniscus regeneration is hindered by the complex, composite nature of the meniscus which exhibit a gradient from inner cartilage-like tissue to outer fibrous tissue, as well as engineering hurdles often requiring growth factors and cross-linking agents. Here, a meniscus zonal tissue gradient is proposed using zone-specific decellularized meniscus extracellular matrix (DMECM) and autologous synovial mesenchymal stem cells (SMSC) via self-aggregation without the use of growth factors or cross-linking agents. Combination with zone-specific DMECM during self-aggregation of MSCs forms zone-specific meniscus tissue that reflects the respective DMECM harvest site. The implantation of these constructs leads to the regeneration of meniscus tissue resembling the native meniscus, demonstrating inner cartilaginous and outer fibrous characteristics as well as recovery of native meniscal microarchitecture in a porcine partial meniscectomy model at 6 months. In all, the findings offer a potential regenerative therapy for DMTs that may improve current partial meniscectomy-based patient care.