Ionizable Polymeric Micelles with Phenylalanine Moieties Enhance Intracellular Delivery of Self-Replicating RNA for Long-Lasting Protein Expression In Vivo.

mRNA-based therapeutics are revolutionizing the landscape of medical interventions. However, the short half-life of mRNA and transient protein expression often limits its therapeutic potential, demanding high treatment doses or repeated administrations. Self-replicating RNA (RepRNA)-based treatments could offer enhanced protein production and reduce the required dosage. Here, we developed polymeric micelles based on flexible poly(ethylene glycol)-poly(glycerol) (PEG-PG) block copolymers modified with phenylalanine (Phe) moieties via biodegradable ester bonds for the efficient delivery of RepRNA. These polymers successfully encapsulated RepRNA into sub-100 nm micelles assisted by the hydrophobicity of the Phe moieties and their ability to π-π stack with the bases in RepRNA. The micelles made from Phe-modified PEG-PG (PEG-PG(Phe)) effectively maintained the integrity of the loaded RepRNA in RNase-rich serum conditions. Once taken up by cells, the micelles triggered a pH-responsive membrane disruption, promoted by the strong protonation of the amino groups at endosomal pH, thereby delivering the RepRNA to the cytosol. The system induced strong protein expression in vitro and outperformed commercial transfecting reagents in vivo, where it resulted in enhanced and long-lasting protein expression.

Microbial Detoxification of Sediments Underpins Persistence of Zostera marina Meadows.

Eelgrass meadows have attracted much attention not only for their ability to maintain marine ecosystems as feeding grounds for marine organisms but also for their potential to store atmospheric and dissolved CO2 as blue carbon. This study comprehensively evaluated the bacterial and chemical data obtained from eelgrass sediments of different scales along the Japanese coast to investigate the effect on the acclimatization of eelgrass. Regardless of the eelgrass habitat, approximately 1% Anaerolineales, Babeliales, Cytophagales, and Phycisphaerales was present in the bottom sediment. Sulfate-reducing bacteria (SRB) were present at 3.69% in eelgrass sediment compared to 1.70% in bare sediment. Sulfur-oxidizing bacteria (SOB) were present at 2.81% and 1.10% in the eelgrass and bare sediment, respectively. Bacterial composition analysis and linear discriminant analysis revealed that SOB detoxified H2S in the eelgrass meadows and that the larger-scale eelgrass meadows had a higher diversity of SOB. Our result indicated that there were regional differences in the system that detoxifies H2S in eelgrass meadows, either microbial oxidation mediated by SOB or O2 permeation via the physical diffusion of benthos. However, since bacterial flora and phylogenetic analyses cannot show bias and/or causality due to PCR, future kinetic studies on microbial metabolism are expected.

Block catiomers with flanking hydrolyzable tyrosinate groups enhance in vivo mRNA delivery via π-π stacking-assisted micellar assembly.

Messenger RNA (mRNA) therapeutics have recently demonstrated high clinical potential with the accelerated approval of SARS-CoV-2 vaccines. To fulfill the promise of unprecedented mRNA-based treatments, the development of safe and efficient carriers is still necessary to achieve effective delivery of mRNA. Herein, we prepared mRNA-loaded nanocarriers for enhanced in vivo delivery using biocompatible block copolymers having functional amino acid moieties for tunable interaction with mRNA. The block copolymers were based on flexible poly(ethylene glycol)-poly(glycerol) (PEG-PG) modified with glycine (Gly), leucine (Leu) or tyrosine (Tyr) via ester bonds to generate block catiomers. Moreover, the amino acids can be gradually detached from the block copolymers after ester bond hydrolyzation, avoiding cytotoxic effects. When mixed with mRNA, the block catiomers formed narrowly distributed polymeric micelles with high stability and enhanced delivery efficiency. Particularly, the micelles based on tyrosine-modified PEG-PG (PEG-PGTyr), which formed a polyion complex (PIC) and π-π stacking with mRNA, displayed excellent stability against polyanions and promoted mRNA integrity in serum. PEG-PGTyr-based micelles also increased the cellular uptake and the endosomal escape, promoting high protein expression both in vitro and in vivo. Furthermore, the PEG-PGTyr-based micelles significantly extended the half-life of the loaded mRNA after intravenous injection. Our results highlight the potential of PEG-PGTyr-based micelles as safe and effective carriers for mRNA, expediting the rational design of polymeric materials for enhanced mRNA delivery.

Case-control study of the correlation between the five times sit to stand and 6-min walk distance in patients with pancreatic cancer.

PURPOSE: Cases of pancreatic cancer are increasing, and the risk of developing this disease reportedly increases with age. In recent years, there has been an increasing number of reports on physical function in patients with pancreatic cancer. Methods such as the 6-min walk distance (6 MWD) should be established to evaluate physical function, as a decline in exercise capacity is an important index in these patients. Recently, the 6 MWD has also been used to evaluate physical function in patients with pancreatic cancer. In healthy older adults, a decrease in 6 MWD is reportedly associated with intrinsic capacity and health status. Such factors make assessing 6 MWD important. However, the measurement of 6 MWD requires a sizable measurement environment. The five times sit to stand (FTSTS) test is a simple method that can be performed using a chair. FTSTS is hypothesized to be a useful assessment scale in patients with pancreatic cancer because it is easy to estimate the decline in physical function in clinical practice if the decline in 6 MWD can be estimated by evaluating FTSTS. The study's purpose was to clarify this hypothesis and ascertain the cutoff required to determine the decrease in 6 MWD in clinical practice. METHODS: Sixty consecutive patients with preoperative pancreatic cancer who were assessed for physical function were studied. 6 MWD (< 400 m) was the objective variable, and binary logistic regression analysis was performed, with age, BMI, sex, FTSTS, and HGS as explanatory variables. Receiver-operating characteristic (ROC) curve analysis was performed for the explanatory variables, which were found to be significant based on logistic regression analysis. The area under the curve (AUC) was also calculated. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were evaluated. This study was approved by Hiroshima University Hospital's ethics committee (approval number: E808-1). RESULTS: Fifty-seven of the 60 patients were included in the analysis. Logistic regression analysis showed that FTSTS was a significant explanatory variable; ROC curve analysis showed an AUC of 0.872 and a cutoff value of 8.98 s. The sensitivity, specificity, PPV, and NPV were 82.4%, 80.0%, 63.6%, and 91.4%, respectively. CONCLUSIONS: A decrease in 6 MWD in preoperative pancreatic cancer patients can be identified by performing FTSTS.

Lactic acid bacterial exopolysaccharides strongly bind histamine and can potentially be used to remove histamine contamination in food.

The symptoms of foodborne histamine poisoning are similar to those of IgE-mediated food allergies. In this study, we investigated the histamine-binding capacity of lactic acid bacteria (LAB) strains as potential preventive agents against histamine poisoning. Histamine biosorption capacity was determined for 16 LAB strains. Leuconostoc mesenteroides TOKAI 51 m, Lactobacillus paracasei TOKAI 65 m, Lactobacillus plantarum TOKAI 111 m and Pediococcus pentosaceus TOKAI 759 m showed especially high biosorption rates and reached saturation within 30 min. Adsorption isotherms showed better conformance to the Freundlich model than to the Langmuir model. Analyses after heat, periodic acid and guanidine hydrochloride treatments suggested that histamine was bound to the bacterial cell surface. HPLC analysis revealed that exopolysaccharides produced by Lact. paracasei TOKAI 65 m strongly bound to histamine. In the detachment test with 1 mol l-1 HCl solution, the dissociation rate of histamine for Lact. paracasei TOKAI 65 m was <10 %. This strain is presumably a suitable candidate for use against histamine poisoning.

Changes in motor function and quality of life after surgery in patients with pancreatic cancer.

OBJECTIVE: To determine the changes in motor function and health-related quality of life after pancreatectomy and identify factors influencing postoperative physical functioning in health-related quality of life. METHODS: This single-centre, prospective, observational study measured 6-min walking distance, grip strength, knee extension strength and health-related quality of life variables in patients with pancreatic cancer, before and after surgery. Paired t- and Wilcoxon signed-rank tests were used to compare pre- and postoperative motor function and health-related quality-of-life variables. Factors associated with postoperative physical functioning scores of health-related quality of life were assessed using multiple regression analysis. RESULTS: Fifty-nine individuals were enrolled. Motor function values decreased significantly postoperatively, including 6-min walking distance (mean ± standard deviation: 402.5 ± 95.4 vs. 497.7 ± 80.4 m, p < 0.001), knee extensor strength (0.42 ± 0.10 vs. 0.47 ± 0.10 kgf/kg, p < 0.001) and grip strength (22.0 ± 8.9 vs. 24.5 ± 9.2 kg, p = 0.001). Multiple regression analysis showed significant association between 6-min walking distance change and postoperative physical functioning scores of health-related quality of life (p = 0.036). CONCLUSION: The results suggest that motor function decreases postoperatively, and a decrease in 6-min walking distance after surgery is associated with postoperative physical functioning in patients with pancreatic cancer.

Anaplastic Carcinoma Arising From Ovarian Mucinous Adenocarcinoma With Massive Cardiopulmonary Metastasis: An Autopsy Case Report.

BACKGROUND: The presence of anaplastic and sarcomatoid components in ovarian mucinous carcinoma is extremely rare. CASE: A 64-year-old woman underwent radical surgery for right ovarian cancer. Pathological examination showed mucinous adenocarcinoma with a focal mural nodule of anaplastic and sarcomatoid carcinoma (FIGO stage IIB). She underwent adjuvant chemotherapy but developed severe respiratory failure and died after 9 months. Autopsy showed that the bilateral pulmonary parenchyma was filled with a multinodular hemorrhagic mass, and the cardiac wall had a massive invasive lesion. Histopathological examination of the lung and myocardium revealed diffuse invasion of the anaplastic carcinoma component with infiltrating osteoclastic giant cells. CONCLUSION: This case is very rare, and the clinical management of anaplastic carcinoma arising in mucinous neoplasms remains challenging.

Thermoelectric properties of sorted semiconducting single-walled carbon nanotube sheets.

Single-walled carbon nanotubes (SWNTs), especially their semiconducting type, are promising thermoelectric (TE) materials due to their high Seebeck coefficient. In this study, the in-plane Seebeck coefficient (S), electrical conductivity (σ), and thermal conductivity (κ) of sorted semiconducting SWNT (s-SWNT) free-standing sheets with different s-SWNT purities are measured to determine the figure of merit ZT. We find that the ZT value of the sheets increases with increasing s-SWNT purity, mainly due to an increase in Seebeck coefficient while the thermal conductivity remaining constant, which experimentally proved the superiority of the high purity s-SWNT as TE materials for the first time. In addition, from the comparison between sorted and unsorted SWNT sheets, it is recognized that the difference of ZT between unsorted SWNT and high-purity s-SWNT sheet is not remarkable, which suggests the control of carrier density is necessary to further clarify the superiority of SWNT sorting for TE applications.

[The Optimal Start Timing of Helical Scan for Coronary CT Angiography and CT Myocardial Perfusion Scan Using 64-MDCT].

PURPOSE: Ichihara et al. (Fujita Med J 2015; 1(1): 9-14) developed a method to simultaneously obtain both coronary computed tomography (CT) angiography and CT myocardial perfusion (CTP) using 64-multi detector CT (MDCT). An input-function (time enhancement curve, TEC) of the ascending aorta (Ao) and myocardial CT density are necessary to calculate absolute myocardial blood flow (ml/g/min) using a two-compartment model. Helical scan starting timing is important to capture the peak (P) of Ao time enhancement curve (TEC). The purpose is to search the optimal timing of starting helical scan to capture the P. METHODS: We performed 14 CTPs using Definition AS+ (SIEMENS). A dynamic scan at the Ao level was started at 7 s after contrast injection and helical scan was started at various trigger on bolus tracking. Definition AS+ needs 2 s (other scanner may need 4 s) for changing from a dynamic to helical scan mode. We created TECs of pulmonary artery (PA) and Ao using the fifth function fitting. We measured the time from trigger point to the P (t200, t250, t300 and tCP). RESULTS: Mean t200, t250, t300 and tCP were 9.1±1.9, 7.9±2.0, 6.6±1.9 and 3.9±1.2 s, respectively. In additional other 16 CTP studies using the cross point method, we can capture the P in all (100%) examinations. CONCLUSION: Scan starting at the cross point is best for Definition AS+, and the Ao=300 HU may be best for other scanner that needs 4 s for changing scan mode to obtain a fine input function for calculating absolute myocardial blood flow.

An extremely rare case of tubo-ovarian abscesses involving corynebacterium striatum as causative agent.

BACKGROUND: We present an extremely rare case of tubo-ovarian abscesses involving Corynebacterium striatum (C. striatum) as causative agent in a 53-year-old woman. CASE PRESENTATION: The patient presented with stomach pain, chills, and nausea. Her medical history included poorly controlled psoriasis vulgaris and diabetes. Laboratory and imaging findings led to diagnosis of septic shock due to tubo-ovarian abscesses. She was treated with antibiotic therapy and surgery to remove the left adnexa. Various cultures detected Prevotella spp. and C. striatum. We concluded that C. striatum from skin contaminated by psoriasis vulgaris had caused the tubo-ovarian abscesses by way of ascending infection. CONCLUSIONS: This may be the first known case of tubo-ovarian abscesses due to C. striatum. In patients whose skin has been weakened by psoriasis vulgaris or other infections, Corynebacterium should be considered as causative microorganisms, and antibiotic therapy including vancomycin should be administered.

Prevalence of fracture progression in fragility fractures of the pelvis: Systematic review and meta-analysis.

BACKGROUND: Fragility fractures of the pelvis (FFP) are a growing problem in aging populations. Fracture progression (FP) occasionally occurs during FFP treatment; however, its prevalence remains unclear. This systematic review and meta-analysis aimed to assess the prevalence of FP among patients with FFP. METHODS: We performed a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. All cohort studies that reported the prevalence of FP in patients with FFP were included. FP was defined as the appearance of additional pelvic fractures after the initial FFP. We searched the CENTRAL, MEDLINE, and EMBASE databases until April 2024. The pooled prevalence was generated using a random-effects model and presented as a 95 % confidence interval (CI) and prediction interval (PI). We assessed the risk of bias in each study using the Joanna Briggs Institute's Prevalence Critical Appraisal Tool. RESULTS: This review included eight studies (925 patients). The pooled prevalence of FP in patients with FFP was 11 % (95 % CI, 5-19 %; 95 % PI, 0-44 %). Subgroup analysis showed that the pooled prevalence of FP in patients with FFP (conservative treatment vs. surgery for initial FFP) was 16 % (95 % CI, 9-24 %) and 2 % (95 % CI, 0-11 %), respectively (test for subgroup difference, P = 0.03). Additional analysis showed that in patients with FP, the pooled prevalence of the fractured site (ipsilateral site, contralateral site, and both sites) was 66 %, 12 %, and 19 %, respectively. The pooled prevalence of fractured bone (pubis, ischium, ilium, and sacrum) was 25 %, 0 %, 15 %, and 68 %, respectively. The risk of bias in the patient sampling method and sufficient data analysis in all included studies was high. CONCLUSION: This review suggests that the prevalence of FP in patients with FFP is relatively high. Clinicians should recognize FP as a possible diagnosis in patients experiencing additional pain after FFP. However, further prospective studies with adequate patient sampling are required to confirm the true prevalence.

Association between a history of major osteoporotic fractures and subsequent hip fracture: a systematic review and meta-analysis.

PURPOSE: A history of fractures involving the distal radius, proximal humerus, spine, and hip may be associated with the incidence of subsequent hip fractures in older people. However, a comprehensive summary of this association using a rigorous methodology is lacking. Our objective was to systematically review the literature and examine the association between four major osteoporotic fractures and subsequent hip fractures in individuals aged ≥ 50 years. METHODS: We searched MEDLINE, Embase, CENTRAL, ICTRP, and ClinicalTrials.gov on February 15, 2023. The search included cohort or case-control studies investigating the association between these four types of osteoporotic fractures and subsequent hip fractures. We pooled the hazard ratios (HRs) with 95% confidence intervals (CI) using the random-effects model. We used the Quality In Prognosis Studies tool to assess the risk of bias in the included studies, and the grading of recommendations assessment, development, and evaluation approach to determine the certainty of evidence. RESULTS: The selection process identified 48 studies for qualitative synthesis and 23 studies (2,239,217 participants) for meta-analysis. The overall methodological quality had a low risk of bias in 65% of the included studies. The association between a history of major osteoporotic fractures and subsequent hip fracture varied, with a high certainty of evidence for a history of proximal humerus and hip fractures (HR 2.02, 95% CI 1.75-2.33 and 2.86, 95% CI 1.92-4.25, respectively), moderate certainty for distal radius fractures (HR 1.66, 95% CI 1.53-1.81), and low certainty for spine fractures (HR 1.53, 95% CI 1.38-1.69). CONCLUSIONS: In conclusion, a history of major osteoporotic fractures, particularly distal radius, proximal humerus, and hip fractures, is associated with subsequent hip fractures in older adults. Further research is needed to verify the association between a history of spine fracture and subsequent hip fractures. PROTOCOL REGISTRATION: Open Science Framework ( https://osf.io/7fjuc ).

Advanced liver fibrosis is associated with decreased gait speed in older patients with chronic liver disease.

This study investigated whether the progression of liver fibrosis affects the prevalence of sarcopenia and incidence of decreased gait speed in older patients with chronic liver disease (CLD). Patients with CLD aged ≥ 60 years were classified into low, intermediate, and high fibrosis 4 (FIB-4) index groups according to the degree of liver fibrosis. The prevalence of sarcopenia and incidence of decreased gait speed (< 1.0 m/s) were compared among the three groups. Logistic regression analysis was performed to investigate factors affecting the risk of decreased gait speed. No significant difference was observed in the prevalence of sarcopenia among the three groups, but the incidence of decreased gait speed significantly differed (p = 0.029). When analyzed individually, a significant difference in decreased gait speed incidence was observed between the high and low FIB-4 index groups (p = 0.014). In logistic regression analysis, the progression of liver fibrosis (odds ratio: 1.32, 95% confidence interval: 1.13-1.55) and lower extremity muscle strength (LEMS) (odds ratio: 0.92, 95% confidence interval: 0.88-0.97) were significantly associated with decreased gait speed. As liver fibrosis progresses in older patients with CLD, it becomes important to focus on not only skeletal muscle mass and grip strength, but also gait speed and LEMS.

Safety and Feasibility of Fan Therapy for Dyspnea: A Scoping Review.

Fan therapy is a non-pharmacological approach useful in terminally ill patients that relieves dyspnea by directing a fan to blow air on one side of the patient's face. To date, there has been no systematic review of fan therapy for critically ill patients in the intensive care unit. This scoping review aimed to provide a comprehensive overview of fan therapy studies published to date, clarify the therapeutic intervention methods of fan therapy, evaluate its safety according to existing literature, and explore its potential use in critically ill patients. A scoping review was conducted using the Joanna Briggs Institute methodology. This scoping review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension of the scoping reviews statement. All published studies conducted on patients who received fan therapy regardless of age, disease, setting, phase, country, or follow-up duration were included. The data sources included Medical Literature Analysis and Retrieval System Online, Embase, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Literature databases. Of the 685 studies obtained, 15 were included, comprising patients with terminal cancer and chronic lung diseases. The most common intervention was a single five-minute intervention for dyspnea at rest. The studies on patients receiving oxygen therapy did not report adverse events or worsening of blood pressure, pulse rate, respiratory rate, or SpO2 levels. However, there are no studies in the literature on the use of fan therapy for critically ill patients. Nevertheless, previous studies suggest that fan therapy is safe.

Efficacy of Pelvic Floor Muscle Training for Postoperative Patients With Rectal Cancer: A Systematic Review and Meta-Analysis.

This study aimed to assess the effectiveness of pelvic floor muscle training (PFMT) for fecal incontinence (FI) and health-related quality of life (HR-QOL) after colorectal cancer surgery. This systematic review (SR) and meta-analysis included randomized controlled trials (RCTs) that examined the effects of PFMT after colorectal cancer surgery, which were extracted from several databases in January 2023. The primary outcomes were FI (Wexner scores), HR-QOL, and adverse events. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence (CoE). A total of seven RCTs were included. Our SR results suggested that PFMT showed little to no difference in FI (mean difference 0.62 higher; 95% CI: -1.26 to 2.5, low CoE) and adverse events (risk ratio 5.78; 95% CI: 0.28-117.22, low CoE). Two adverse events occurred in the PFMT group (anastomotic stenosis, suboptimal use of laxatives) and were not observed in controls. HR-QOL was measured in two RCTs using 12-item Short Form Survey (SF-12) and fecal incontinence quality of life (FIQL). Two RCTs found no trend toward a positive impact on HR-QOL. Higher quality RCTs on colorectal cancer after surgery are required. Furthermore, extending the duration of the PFMT intervention may be necessary to ensure its success.

Efficacy of neuromuscular electrical stimulation for thoracic and abdominal surgery: A systematic review and meta-analysis.

This systematic review and meta-analysis examined the efficacy of neuromuscular electrical stimulation (NMES) on lower limb muscle strength and health-related quality of life (HR-QOL) after thoracic and abdominal surgery. We searched the Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, Excerpta Medica Database via Elsevier, Physiotherapy Evidence Database, Cumulative Index to Nursing and Allied Health Literature, World Health Organization International Clinical Trials Registry Platform via their dedicated search portal, and ClinicalTrials.gov on November 2021 and updated in April 2023 to identify randomized controlled trials that examined the effects of NMES after thoracic and abdominal surgery. The primary outcomes were lower limb muscle strength, HR-QOL, and adverse events. We used the Cochrane Risk of Bias Tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess the certainty of evidence. A total of 18 randomized control trials involving 915 participants, including 10 on cardiovascular surgery, two on pulmonary surgery, five on digestive system surgery, and one on other surgery, were included. NMES slightly increased lower limb muscle strength and adverse events in cardiovascular surgery. Adverse events (hypotension, pain, and muscle discomfort) occurred in seven patients. HR-QOL was measured in two studies on cardiovascular surgery, but these were not pooled due to concept heterogeneity. Overall, NMES slightly increases lower limb muscle strength after cardiovascular surgery without serious adverse events. However, higher-quality randomized control trials in thoracic and abdominal surgeries are needed.

Identification of a pluripotency-inducing small compound, PLU, that induces callus formation via Heat Shock Protein 90-mediated activation of auxin signaling.

Plants retain the ability to generate a pluripotent tissue called callus by dedifferentiating somatic cells. A pluripotent callus can also be artificially induced by culturing explants with hormone mixtures of auxin and cytokinin, and an entire body can then be regenerated from the callus. Here we identified a pluripotency-inducing small compound, PLU, that induces the formation of callus with tissue regeneration potency without the external application of either auxin or cytokinin. The PLU-induced callus expressed several marker genes related to pluripotency acquisition via lateral root initiation processes. PLU-induced callus formation required activation of the auxin signaling pathway though the amount of active auxin was reduced by PLU treatment. RNA-seq analysis and subsequent experiments revealed that Heat Shock Protein 90 (HSP90) mediates a significant part of the PLU-initiated early events. We also showed that HSP90-dependent induction of TRANSPORT INHIBITOR RESPONSE 1, an auxin receptor gene, is required for the callus formation by PLU. Collectively, this study provides a new tool for manipulating and investigating the induction of plant pluripotency from a different angle from the conventional method with the external application of hormone mixtures.

Multimodality imaging to identify lipid-rich coronary plaques and predict periprocedural myocardial injury: Association between near-infrared spectroscopy and coronary computed tomography angiography.

Background: This study compares the efficacy of coronary computed tomography angiography (CCTA) and near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with significant coronary stenosis for predicting periprocedural myocardial injury during percutaneous coronary intervention (PCI). Methods: We prospectively enrolled 107 patients who underwent CCTA before PCI and performed NIRS-IVUS during PCI. Based on the maximal lipid core burden index for any 4-mm longitudinal segments (maxLCBI4mm) in the culprit lesion, we divided the patients into two groups: lipid-rich plaque (LRP) group (maxLCBI4mm ≥ 400; n = 48) and no-LRP group (maxLCBI4mm < 400; n = 59). Periprocedural myocardial injury was a postprocedural cardiac troponin T (cTnT) elevation of ≥5 times the upper limit of normal. Results: The LRP group had a significantly higher cTnT (p = 0.026), lower CT density (p < 0.001), larger percentage atheroma volume (PAV) by NIRS-IVUS (p = 0.036), and larger remodeling index measured by both CCTA (p = 0.020) and NIRS-IVUS (p < 0.001). A significant negative linear correlation was found between maxLCBI4mm and CT density (rho = -0.552, p < 0.001). Multivariable logistic regression analysis identified maxLCBI4mm [odds ratio (OR): 1.006, p = 0.003] and PAV (OR: 1.125, p = 0.014) as independent predictors of periprocedural myocardial injury, while CT density was not an independent predictor (OR: 0.991, p = 0.22). Conclusion: CCTA and NIRS-IVUS correlated well to identify LRP in culprit lesions. However, NIRS-IVUS was more competent in predicting the risk of periprocedural myocardial injury.

Spred-2 deficiency exacerbates acetaminophen-induced hepatotoxicity in mice.

MAPKs are involved in acetaminophen (APAP)-hepatotoxicity, but the regulatory mechanism remains unknown. Here, we explored the role of Spred-2 that negatively regulates Ras/ERK pathway in APAP-hepatotoxicity. Spred-2 knockout (KO) mice demonstrated exacerbated liver injury, an event that was associated with increased numbers of CD4(+) T, CD8(+) T and NK cells in the liver compared to the control. Levels of CXCL9/CXCL10 that attract and activate these cells were increased in Spred-2 KO-liver. Kupffer cells isolated from Spred-2 KO mice after APAP challenge expressed higher levels of CXCL9/CXCL10 than those from the control. Upon stimulation with APAP or IFNγ, naïve Kupffer cells from Spred-2 KO mice expressed higher levels of CXCL9/CXCL10. NK cell-depletion attenuated APAP-hepatotoxicity with lowered hepatic IFNγ and decreased numbers of not only NK cells but also CD4(+) T and CD8(+) T cells in the liver. These results suggest that Spred-2 negatively regulates APAP-hepatotoxicity under the control of Kupffer cells and NK cells.