Nanoplastics causes heart aging/myocardial cell senescence through the Ca2+/mtDNA/cGAS-STING signaling cascade.

BACKGROUND: Nanoplastics (NPs) are now a new class of pollutants widely present in the soil, atmosphere, freshwater and marine environments. Nanoplastics can rapidly penetrate cell membranes and accumulate in human tissues and organs, thus posing a potential threat to human health. The heart is the main power source of the body. But up to now, the toxicological effects of long-term exposure to nanoplastics on the heart has not been revealed yet. RESULTS: We evaluated the effects of long term exposure of nanoplastics on cardiac cell/tissue in vitro and in vivo model. Furthermore, we explored the molecular mechanism by which nanoplastics exposure causes myocardial cell senescence. Immunohistochemistry, indirect immunofluorescence and ELISA were performed to detect the effects of nanoplastics on heart aging. We found that nanoplastics were able to induce significant cardiac aging through a series of biochemical assays in vivo. In vitro, the effects of nanoplastics on cardiac cell were investigated, and found that nanoplastics were able to internalize into cardiomyocytes in time and dose-dependant manner. Further biochemical analysis showed that nanoplastics induces cardiomyocytes senescence by detecting a series of senescence marker molecules. Molecular mechanism research shows that nanoplastics may cause mitochondrial destabilization by inducing oxidative stress, which leads to the leakage of mtDNA from mitochondria into the cytoplasm, and then cytoplasm-localized mt-DNA activates the cGAS-STING signaling pathway and promotes inflammation response, ultimately inducing cardiomyocytes senescence. CONCLUSIONS: In this work, we found that nanoplastics exposure induces premature aging of heart. Current research also reveals the molecular mechanism by which nanoplastics induces cardiomyocyte senescence. This study laid the foundation for further studying the potential harm of nanoplastics exposure on heart.

HDAC Inhibitors Alleviate Uric Acid-Induced Vascular Endothelial Cell Injury by Way of the HDAC6/FGF21/PI3K/AKT Pathway.

ABSTRACT: Uric acid (UA) accumulation triggers endothelial dysfunction, oxidative stress, and inflammation. Histone deacetylase (HDAC) plays a vital role in regulating the pathological processes of various diseases. However, the influence of HDAC inhibitor on UA-induced vascular endothelial cell injury (VECI) remains undefined. Hence, this study aimed to investigate the effect of HDACs inhibition on UA-induced vascular endothelial cell dysfunction and its detailed mechanism. UA was used to induce human umbilical vein endothelial cell (HUVEC) injury. Meanwhile, potassium oxonate-induced and hypoxanthine-induced hyperuricemia mouse models were also constructed. A broad-spectrum HDAC inhibitor trichostatin A (TSA) or selective HDAC6 inhibitor TubastatinA (TubA) was given to HUVECs or mice to determine whether HDACs can affect UA-induced VECI. The results showed pretreatment of HUVECs with TSA or HDAC6 knockdown-attenuated UA-induced VECI and increased FGF21 expression and phosphorylation of AKT, eNOS, and FoxO3a. These effects could be reversed by FGF21 knockdown. In vivo, both TSA and TubA reduced inflammation and tissue injury while increased FGF21 expression and phosphorylation of AKT, eNOS, and FoxO3a in the aortic and renal tissues of hyperuricemia mice. Therefore, HDACs, especially HDAC6 inhibitor, alleviated UA-induced VECI through upregulating FGF21 expression and then activating the PI3K/AKT pathway. This suggests that HDAC6 may serve as a novel therapeutic target for treating UA-induced endothelial dysfunction.

Mediating effect of resilience on the relationship between perceived social support and burnout among Chinese palliative nurses.

AIMS AND OBJECTIVES: To detect the mediating effect of resilience on the relationship between perceived social support and burnout in Chinese palliative nurses. BACKGROUND: Palliative nurses are a group that is vulnerable to burnout. Perceived social support may contribute to decreasing palliative nurses' burnout and facilitating their personal resilience, and resilience may be associated with lower levels of burnout. However, these relationships were unclear in the Chinese context. DESIGN: A cross-sectional design. METHODS: The STROBE guideline was performed to report this study. A mixed sampling method including convenience sampling and stratified sampling was used to recruit participants, and a total of 319 palliative nurses completed the Nursing Burnout Scale, the Perceived Social Support Scale and the Connor-Davidson Resilience Scale from May 2021 to September 2021. Influencing factors were primarily identified using independent-sample t tests and one-way ANOVA. Bootstrap method was used to detect the mediating effect of resilience. RESULTS: The level of burnout in palliative nurses (23.4 ± 7.68) was higher than that of general nurses in China. Education level, health condition and monthly income were influencing factors of burnout. Resilience was detected as a mediator in the relationships between perceived social support and dimensions of burnout. CONCLUSIONS: Chinese palliative nurses experience a relatively high level of burnout, which may be influenced by several sociodemographic variables. Resilience could mediate the effect of perceived social support on the dimensions of burnout. Problem-oriented and palliative-tailored strategies should be developed to further address burnout in Chinese palliative nurses. RELEVANCE TO CLINICAL PRACTICE: Nurse managers and policy makers should support nurse ongoing education, adopt health-promoting interventions and optimise salary systems. In addition, perceived social support resources and resilience training programmes are also warranted. PATIENT OR PUBLIC CONTRIBUTION: All participants were invited to complete the informed consent form and paper questionnaires. Human resource managers helped us collect some subjective data through the personnel management system. Nurse managers of palliative units conducted regular staff meetings to promote the data collection process.

Caregiver burden among family caregivers of patients with advanced cancer in a palliative context: A mixed-method study.

AIM: To examine the multidimensional properties of caregiver burden among family caregivers of patients with advanced cancer in a palliative context. DESIGN: A sequential, explanatory, mixed-method study was performed. METHODS: Family caregivers of patients diagnosed with advanced cancer were recruited from a palliative care department of a third-level hospital in Sichuan Province, China. The Caregiver Burden Inventory, Social Support Rating Scale and Connor-Davidson Resilience Scale were used to collect quantitative data, and a total of 150 caregivers were recruited from January 2022 to September 2022. Qualitative data were collected through semi-structured interviews, and a total of 22 caregivers were interviewed from October 2022 to November 2022. Survey data were analysed using descriptive statistics, and the factors of caregiver burden were identified using the Mann-Whitney U test, Kruskal-Wallis H test and Spearman correlations. Interpretative phenomenological analysis was performed to analyse the interview data to initially explore the multidimensions of caregiver burden. The following-a-thread method and convergence coding matrix were used for triangulation to examine the multidimensional properties of caregiver burden. RESULTS: The participants experienced a moderate level of caregiver burden (32.97 ± 13.09). Through triangulation, six meta-themes and nine meta-subthemes were identified as multidimensional properties of caregiver burden, including physical (too many caring tasks and poor health condition), emotional (strong negative emotions resulting from patients' suffering and insufficient and ineffective family communication), social (less social interaction and social role conflict) and economic burdens, factors that aggravate burden (prevention and control of COVID-19 and spousal relationship with patients) and factors that mitigate burden (social support). CONCLUSION: Multiple dimensions of caregiver burden were experienced by family caregivers of patients with advanced cancer in the palliative context. Family-centred palliative care must be further developed. IMPLICATIONS FOR THE PROFESSION: It is important to develop family-centred palliative care. Therefore, the focus must be on developing a rational understanding of palliative care in public and a culture-oriented death education in palliative units. IMPACT: This study adopted a mixed-method approach to comprehensively understand the phenomenon of and factors in caregiver burden in the Chinese palliative oncology context. Our findings suggest that family caregivers in palliative oncology experience a moderate level of caregiver burden, with dimensions including physical, emotional, social and economic burdens, among which emotional burden is the most prominent. The findings of this study provide policy makers and nurse practitioners with targets to be addressed in family-centred care in Chinese palliative units. REPORTING METHOD: The results of this study are reported based on the guidelines of the Mixed-Methods Article Reporting Standards. PATIENT OR PUBLIC CONTRIBUTION: Eligible caregivers were invited to participate in the study and semi-structured interviews. Nurse managers of the palliative unit helped us access the patient-management system.

[MicroRNA-22-3p Regulates the Expression of Kruppel-like Factor 6 to Affect the Cardiomyocyte-like Differentiation of Bone Marrow Mesenchymal Stem Cell].

Objective To explore the effect of microRNA-22-3p (miR-22-3p) regulating the expression of Kruppel-like factor 6 (KLF6) on the cardiomyocyte-like differentiation of bone marrow mesenchymal stem cell (BMSC). Methods Rat BMSC was isolated and cultured,and the third-generation BMSC was divided into a control group,a 5-azacytidine(5-AZA)group,a mimics-NC group,a miR-22-3p mimics group,a miR-22-3p mimics+pcDNA group,and a miR-22-3p mimics+pcDNA-KLF6 group.Real-time fluorescent quantitative PCR (qRT-PCR) was carried out to determine the expression of miR-22-3p and KLF6 in cells.Immunofluorescence staining was employed to detect the expression of Desmin,cardiac troponin T (cTnT),and connexin 43 (Cx43).Western blotting was employed to determine the protein levels of cTnT,Cx43,Desmin,and KLF6,and flow cytometry to detect the apoptosis of BMSC.The targeting relationship between miR-22-3p and KLF6 was analyzed by dual luciferase reporter gene assay. Results Compared with the control group,5-AZA up-regulated the expression of miR-22-3p (q=7.971,P<0.001),Desmin (q=7.876,P<0.001),cTnT (q=10.272,P<0.001),and Cx43 (q=6.256,P<0.001),increased the apoptosis rate of BMSC (q=12.708,P<0.001),and down-regulated the mRNA (q=20.850,P<0.001) and protein (q=11.080,P<0.001) levels of KLF6.Compared with the 5-AZA group and the mimics-NC group,miR-22-3p mimics up-regulated the expression of miR-22-3p (q=3.591,P<0.001;q=11.650,P<0.001),Desmin (q=5.975,P<0.001;q=13.579,P<0.001),cTnT (q=7.133,P<0.001;q=17.548,P<0.001),and Cx43 (q=4.571,P=0.037;q=11.068,P<0.001),and down-regulated the mRNA (q=7.384,P<0.001;q=28.234,P<0.001) and protein (q=4.594,P=0.036;q=15.945,P<0.001) levels of KLF6.The apoptosis rate of miR-22-3p mimics group was lower than that of 5-AZA group (q=8.216,P<0.001).Compared with the miR-22-3p mimics+pcDNA group,miR-22-3p mimics+pcDNA-KLF6 up-regulated the mRNA(q=23.891,P<0.001) and protein(q=13.378,P<0.001)levels of KLF6,down-regulated the expression of Desmin (q=9.505,P<0.001),cTnT (q=10.985,P<0.001),and Cx43 (q=8.301,P<0.001),and increased the apoptosis rate (q=4.713,P=0.029).The dual luciferase reporter gene experiment demonstrated that KLF6 was a potential target gene of miR-22-3p. Conclusion MiR-22-3p promotes cardiomyocyte-like differentiation of BMSC by inhibiting the expression of KLF6.

Establishing the optimal duration of DAPT following PCI in high-risk TWILIGHT-like patients with acute coronary syndrome.

OBJECTIVES: To determine the association of extended-term (>12-month) versus short-term dual antiplatelet therapy (DAPT) with ischemic and hemorrhagic events in high-risk "TWILIGHT-like" patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) in clinical practice. BACKGROUND: Recent emphasis on shorter DAPT regimen after PCI irrespective of indication for PCI may fail to account for the substantial residual risk of recurrent atherothrombotic events in ACS patients. METHODS: All consecutive patients fulfilling the "TWILIGHT-like" criteria undergoing PCI were identified from the prospective Fuwai PCI Registry. High-risk patients (n = 8,358) were defined by at least one clinical and one angiographic feature based on TWILIGHT trial selection criteria. The primary ischemic endpoint was major adverse cardiac and cerebrovascular events at 30 months, composed of all-cause mortality, myocardial infarction, or stroke while BARC type 2, 3, or 5 bleeding was key secondary outcome. RESULTS: Of 4,875 high-risk ACS patients who remained event-free at 12 months after PCI, DAPT>12-month compared with shorter DAPT reduced the primary ischemic endpoint by 63% (1.5 vs. 3.8%; HRadj: 0.374, 95% CI: 0.256-0.548; HRmatched: 0.361, 95% CI: 0.221-0.590). The HR for cardiovascular death was 0.049 (0.007-0.362) and that for MI 0.45 (0.153-1.320) and definite/probable stent thrombosis 0.296 (0.080-1.095) in propensity-matched analyses. Rates of BARC type 2, 3, or 5 bleeding (0.9 vs. 1.3%; HRadj: 0.668 [0.379-1.178]; HRmatched: 0.721 [0.369-1.410]) did not differ significantly between two groups. CONCLUSIONS: Among high-risk ACS patients undergoing PCI, long-term DAPT, compared with shorter DAPT, reduced ischemic events without a concomitant increase in clinically meaning bleeding events, suggesting that prolonged DAPT can be considered in ACS patients who present with a particularly higher risk for thrombotic complications without excessive risk of bleeding.

Thrombotic vs. Bleeding Events of Interruption of Dual Antiplatelet Therapy within 12 Months among Patients with Stent-Driven High Ischemic Risk Definition following PCI.

BACKGROUND: There is a paucity of real-world data regarding the clinical impact of dual antiplatelet therapy (DAPT) interruption (temporary or permanent) among patients at high ischemic risk. The aim of this study was to assess the risk of cardiovascular events after interruption of DAPT in high-risk PCI population. METHODS: This study used data from the Fuwai PCI registry, a large, prospective cohort of consecutive patients who underwent PCI. We assessed 3,931 patients with at least 1 high ischemic risk criteria of stent-related recurrent ischemic events proposed in the 2017 ESC guidelines for focused update on DAPT who were free of major cardiac events in the first 12 months. The primary ischemic endpoint was 30-month major adverse cardiac and cerebrovascular events, and the key safety endpoints were BARC class 2, 3, or 5 bleeding and net adverse clinical events. RESULTS: DAPT interruption within 12 months occurred in 1,122 patients (28.5%), most of which were due to bleeding events or patients' noncompliance to treatment. A multivariate Cox regression model, propensity score (PS) matching, and inverse probability of treatment weighting (IPTW) based on the propensity score demonstrated that DAPT interruption significantly increased the risk of primary ischemic endpoint compared with prolonged DAPT (3.9% vs. 2.2%; Cox-adjusted hazard ratio (HR): 1.840; 95% confidence interval (CI): 1.247 to 2.716; PS matching-HR: 2.049 [1.236-3.399]; IPTW-adjusted HR: 1.843 [1.250-2.717]). This difference was driven mainly by all-cause death (1.8% vs. 0.7%) and MI (1.3% vs. 0.5%). Furthermore, the rate of net adverse clinical events (4.9% vs. 3.2%; Cox-adjusted HR: 1.581 [1.128-2.216]; PS matching-HR: 1.639 [1.075-2.499]; IPTW-adjusted HR: 1.554 [1.110-2.177]) was also higher in patients with DAPT interruption (≤12 months), whereas no significant differences between groups were observed in terms of BARC 2, 3, or 5 bleeding. These findings were consistent across various stent-driven high-ischemic risk subsets with respect to the primary ischemic endpoints, with a greater magnitude of harm among patients with diffuse multivessel diabetic coronary artery disease. CONCLUSIONS: In patients undergoing high-risk PCI, interruption of DAPT in the first 12 months occurred infrequently and was associated with a significantly higher adjusted risk of major adverse cardiovascular events and net adverse clinical events. 2017 ESC stent-driven high ischemic risk criteria may help clinicians to discriminate patient selection in the use of long-term DAPT when the ischemic risk certainly overcomes the bleeding one.

Status and related factors of burnout among palliative nurses in China: a cross-sectional study.

BACKGROUND: Burnout occurs frequently in nurses and seems more common in nurses providing palliative care. However, to our knowledge, there is a lack of understanding regarding the factors influencing burnout among palliative nurses in China. METHODS: A cross-sectional design was conducted. A total of 331 palliative nurses from 25 hospitals participated in this study. Anonymous data were collected through a self-designed social-demographic questionnaire, the Nursing Burnout Scale, the Perceived Social Support Scale, the General Self-Efficacy Scale, the Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire. Independent sample t tests, one-way ANOVA, Pearson correlations, and multiple linear regressions were performed to identify the related factors of the three dimensions of burnout. RESULTS: In the results of multiple linear regression, resilience, health condition, coping style, and pessimistic personality were common related factors; in addition, end-of-life care training, social support, and income satisfaction were statistically significantly associated with burnout. These factors could explain 38.6%, 27.8%, and 34.5% of the total variance in emotional exhaustion, depersonalization, and reduced personal accomplishment, respectively. CONCLUSIONS: The findings of this study help policy makers and nurse managers better understand burnout among palliative nurses in China. The results highlighted the importance of implementing culture-oriented training programs, providing perceived organizational support, and building a reasonable salary system to decrease burnout among palliative nurses, increase the quality of nursing and promote the development of Chinese palliative care.

Compassion fatigue and compassion satisfaction among Chinese palliative care nurses: A province-wide cross-sectional survey.

AIMS: We aim to explore the prevalence and potential facilitators and inhibitors of compassion fatigue and compassion satisfaction among Chinese palliative care nurses. BACKGROUND: Nurses with compassion fatigue may suffer from health-related problems, causing decreased work efficiency and quality of care. Palliative care nurses are especially at risk of compassion fatigue due to close contact with terminal patients. METHODS: A province-wide cross-sectional survey using convenience sampling was conducted among 318 palliative care nurses at 25 hospitals and healthcare institutions in Sichuan Province, China. Data were collected using demographic questionnaire and five scales: Professional Quality of Life Scale, General Self-Efficacy Scale, Perceived Social Support Scale, Simplified Coping Style Questionnaire, and Connor-Davison Resilience Scale. Data analyses including descriptive statistics, t-test, one-way ANOVA, simple linear regression, and multiple linear regression. RESULTS: Mean scores (SD) for burnout, secondary traumatic stress, and compassion satisfaction were 25.42 (4.75), 26.08 (5.72), and 35.67 (5.77), respectively. Related factors predicted 40.30%, 27.10%, and 35.4% of the variance in the model of burnout, secondary traumatic stress, and compassion satisfaction, respectively (all p < .001). CONCLUSIONS: The levels of burnout and secondary traumatic stress among Chinese palliative care nurses were higher than those among other types of nurses. Social support, resilience, positive coping, family recognition of work, and income satisfaction are inhibitors of compassion fatigue among palliative care nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing administrators and educators should consider providing effective and targeted strategies (e.g. ongoing training and psychological interventions) to decrease compassion fatigue among palliative care nurses based on the cultural and ethical settings.

Interleukin-33 alleviates diabetic cardiomyopathy through regulation of endoplasmic reticulum stress and autophagy via insulin-like growth factor-binding protein 3.

Prolonged endoplasmic reticulum (ER) stress is the key driving force behind diabetic cardiomyopathy (DCM). Autophagy is extensively implicated in adaptive mechanisms for cell survival. Interleukin-33 (IL-33) is known to be a potent cardiac protector, but its roles in DCM, ER stress, and autophagy are currently unknown. We aimed to explore the effects of IL-33 on DCM and characterize the roles that ER stress and autophagy play in DCM. The effects of IL-33 on DCM, ER stress, and autophagy were characterized both in db/db mice and in palmitic acid (PA)-treated cardiomyocytes. The manipulators of ER stress and autophagy were used to clarify their roles in DCM remittance conferred by IL-33. Gene expression analysis was used to identify IL-33-dependent regulators of ER stress and autophagy. Both db/db mice and PA-treated cells presented with enhanced levels of ER stress, apoptosis, and lipid deposition, as well as impaired autophagy, all of which could be reversed by IL-33. Treatment with IL-33 improved the cardiac diastolic function of diabetic mice. Nonselective autophagy inhibitors, such as 3-methyladenine (3-MA) or wortmannin, abolished the protective effects of IL-33, resulting in an increase in both ER stress and apoptosis. Strikingly, insulin-like growth factor-binding protein 3 (IGFBP3) was identified as the gene most significantly differentially expressed between IL-33 and control groups. Knockdown of IGFBP3 expression, similar to the effect of nonselective autophagy inhibitors, resulted in high levels of ER stress, impaired autophagy, and apoptosis that were not rescued upon treatment with IL-33. IL-33 abates DCM by alleviating ER stress and promoting autophagy. IGFBP3 is essential for IL-33-induced ER stress resolution and autophagic enhancement during DCM.

[Correlation between Ameliorated Kawashima Itch Scale and Visual Analogue Scale].

Objective To preliminarily validate the clinical usability of the ameliorated Kawashima Itch Scale(Xie-Kawashima Itch Scale) among adult pruritic patients on maintenance hemodialysis. Methods Xie-Kawashima Itch Scale was developed on the basis of Kawashima Itch Scale. Patients were asked to record their pruritus condition according to Xie-Kawashima Itch Scale or visual analogue scale(VAS) during daytime and night for two weeks. The record at the second week was used for analyzing the correlation between Xie-Kawashima Itch Scale and VAS. Results Totally 134 patients were enrolled in this study,among whom 128 entered the final analysis. Xie-Kawashima Itch Scale was positively correlated with VAS(rs=0.832,95% CI=0.810-0.851,P<0.01 for daytime record;and rs=0.848,95% CI=0.828-0.865,P<0.01 for night record). Subgroup analysis also showed similar correlations between different age groups and among different gender groups. Conclusion Xie-Kawashima Itch Scale has good correlation with VAS in patients on hemodialysis,without being affected by age or gender. Thus,it can be a useful tool for the assessment of pruritus in clinical practice and research.

Biosensor-assisted transcriptional regulator engineering for Methylobacterium extorquens AM1 to improve mevalonate synthesis by increasing the acetyl-CoA supply.

Acetyl-CoA is not only an important intermediate metabolite for cells but also a significant precursor for production of industrially interesting metabolites. Methylobacterium extorquens AM1, a model strain of methylotrophic cell factories using methanol as carbon source, is of interest because it produces abundant coenzyme A compounds capable of directing to synthesis of different useful compounds from methanol. However, acetyl-CoA is not always efficiently accumulated in M. extorquens AM1, as it is located in the center of three cyclic central metabolic pathways. Here we successfully demonstrated a strategy for sensor-assisted transcriptional regulator engineering (SATRE) to control metabolic flux re-distribution to increase acetyl-CoA flux from methanol for mevalonate production in M. extorquens AM1 with introduction of mevalonate synthesis pathway. A mevalonate biosensor was constructed and we succeeded in isolating a mutated strain (Q49) with a 60% increase in mevalonate concentration (an acetyl-CoA-derived product) following sensor-based high-throughput screening of a QscR transcriptional regulator library. The mutated QscR-49 regulator (Q8*,T61S,N72Y,E160V) lost an N-terminal α-helix and underwent a change in the secondary structure of the RD-I domain at the C terminus, two regions that are related to its interaction with DNA. 13C labeling analysis revealed that acetyl-CoA flux was improved by 7% and transcriptional analysis revealed that QscR had global effects and that two key points, NADPH generation and fumC overexpression, might contribute to the carbon flux re-distribution. A fed-batch fermentation in a 5-L bioreactor for QscR-49 mutant yielded a mevalonate concentration of 2.67g/L, which was equivalent to an overall yield of 0.055mol acetyl-CoA/mol methanol, the highest yield among engineered strains of M. extorquens AM1. This work was the first attempt to regulate M. extorquens AM1 on transcriptional level and provided molecular insights into the mechanism of carbon flux regulation.

Developmental changes in digestive enzyme activity in American shad, Alosa sapidissima, during early ontogeny.

In order to assess the digestive physiological capacity of the American shad Alosa sapidissima and to establish feeding protocols that match larval nutritional requirements, we investigated the ontogenesis of digestive enzymes (trypsin, amylase, lipase, pepsin, alkaline phosphatase, and leucine aminopeptidase) in larvae, from hatching to 45 days after hatching (DAH). We found that all of the target enzymes were present at hatching, except pepsin, which indicated an initial ability to digest nutrients and precocious digestive system development. Trypsin rapidly increased to a maximum at 14 DAH. Amylase sharply increased until 10 DAH and exhibited a second increase at 33 DAH, which coincided with the introduction of microdiet at 30 DAH, thereby suggesting that the increase was associated with the microdiet carbohydrate content. Lipase increased until 14 DAH, decreased until 27 DAH, and then increased until 45 DAH. Pepsin was first detected at 27 DAH and then sharply increased until 45 DAH, which suggested the formation of a functional stomach. Both alkaline phosphatase and leucine aminopeptidase markedly increased until 18 DAH, which indicated intestinal maturation. According to our results, we conclude that American shad larvae possess the functional digestive system before mouth opening, and the significant increases in lipase, amylase, pepsin, and intestinal enzyme activities between 27 and 33 DAH suggest that larvae can be successfully weaned onto microdiets around this age.

Nanocomposites of tantalum-based pyrochlore and indium hydroxide showing high and stable photocatalytic activities for overall water splitting and carbon dioxide reduction.

Nanocomposites of tantalum-based pyrochlore nanoparticles and indium hydroxide were prepared by a hydrothermal process for UV-driven photocatalytic reactions including overall water splitting, hydrogen production from photoreforming of methanol, and CO2 reduction with water to produce CO. The best catalyst was more than 20 times more active than sodium tantalate in overall water splitting and 3 times more active than Degussa P25 TiO2 in CO2 reduction. Moreover, the catalyst was very stable while generating stoichiometric products of H2 (or CO) and O2 throughout long-term photocatalytic reactions. After the removal of In(OH)3, the pyrochlore nanoparticles remained highly active for H2 production from pure water and aqueous methanol solution. Both experimental studies and density functional theory calculations suggest that the pyrochlore nanoparticles catalyzed the water reduction to produce H2, whereas In(OH)3 was the major active component for water oxidation to produce O2.

Tyrobp deficiency blocks NLRP3-mediated inflammation and pyroptosis to alleviate myocardial ischemia-reperfusion injury through regulating Syk.

PURPOSE: The present study aims to investigate the biological function of Tyrobp in myocardial ischemia-reperfusion injury (MIRI) and to clarify its potential reaction mechanisms. METHODS: AC16 cells were induced by oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate the MIRI in vitro. The cell transfection technology was used to downregulate Tyrobp, followed by assessment of cell damage, apoptosis and cytokines production via Cell Counting Kit (CCK)-8 assay, lactate dehydrogenase (LDH) release assay, TUNEL and ELISA assays, respectively. Immunofluorescence assay was performed to assess GSDMD. Corresponding proteins were detected via western blotting, and Co-immunoprecipitation (Co-IP) assay was used to validate proteins interaction. RESULTS: Tyrobp was upregulated in OGD/R-exposed AC16 cells, and Tyrobp deficiency significantly alleviated OGD/R-caused cell viability loss, LDH release and cell apoptosis in AC16 cells. Meanwhile, Tyrobp deficiency inhibited the activation of NLRP3 inflammasome, reduced the production of cytokines and inhibited GSDMD intensity and GSDMD-N expression. Additionally, Tyrobp could interact with Syk and regulate Syk/NF-κB signaling. The rescue experiments showed that the above effects of Tyrobp deficiency on OGD/R-exposed AC16 cells were partly weakened by Syk overexpression. CONCLUSION: Tyrobp deficiency alleviated MIRI by inhibiting NLRP3-mediated inflammation and pyroptosis through regulating Syk, providing a novel target for the treatment of MIRI.

Cardiovascular prognosis in patients with type 2 diabetes mellitus mediated by the functional completeness after revascularization.

BACKGROUND: Functional complete revascularization (CR) after percutaneous coronary intervention (PCI), as assessed by the residual functional SYNTAX score (rFSS), has been correlated with enhanced prognostic outcomes. METHODS: A total of 1,555 patients with available post-PCI quantitative flow ratio (QFR) were included, whose data were collected from PANDA III trial. Functional CR was defined as rFSS=0, while anatomic CR was defined as residual SYNTAX score (rSS) = 0. Structural equation modeling was used to analysis whether functional CR explained the relationship between T2DM (Type 2 diabetes mellitus) and the risk of 2-year rates of major adverse cardiac events (including all-cause death, all myocardial infarction, or any ischemia-driven revascularization). RESULTS: Multiple cox regression revealed that T2DM was associated with MACE (P=0.007), but not after adding functional CR to the model (P=0.05), suggesting a mediation effect. Structural equation modeling analysis revealed a significant indirect effect of T2DM on MACE through functional CR (P=0.006, Mediated [%] = 27.3), suggesting a partial mediation effect. CONCLUSION: The degree of functional revascularization may emerge as a central mechanism pivotal in elucidating the association between T2DM and the risk of MACE. Cardiologists should prioritize functional complete revascularization during the initial PCI procedure for patients with diabetes mellitus.

Mediating effect of social support between caregiver burden and quality of life among family caregivers of cancer patients in palliative care units.

PURPOSE: To identify factors influencing the quality of life of family caregivers with terminal cancer in Chinese palliative wards and to test whether social support mediates the relationship between caregiver burden and caregiver quality of life. METHODS: A cross-sectional study design was used. Sociodemographic data were collected and the Quality of Life Scale, the Caregiver Burden Scale, and the Social Support Rating Scale were administered to Chinese family caregivers from December 2021 to December 2022. The factors influencing quality of life and caregiver burden were examined using the Mann‒Whitney U test and the Kruskal‒Wallis H test. The mediating role of social support was assessed using the bootstrap method. RESULTS: Family caregivers' quality of life in Chinese terminal cancer palliative units was related to caregivers' daily care time, the caregiver-patient relationship, and patient age. Caregiver quality of life was negatively associated with caregiver burden and positively associated with social support. In addition, social support mediated the relationship between caregiver burden and caregiver quality of life. CONCLUSION: Social support mediated the impact of caregiver burden on caregiver quality of life. Family, society, and palliative care institutions should be integrated to take actions to reduce family caregiver burden, increase social support, and transfer the positive aspects of specific cultural contexts to the culture of palliative care in general to collaboratively cope with various problems related to end-stage cancer.

Development and validation of a model integrating clinical and coronary lesion-based functional assessment for long-term risk prediction in PCI patients.

OBJECTIVES: To establish a scoring system combining the ACEF score and the quantitative blood flow ratio (QFR) to improve the long-term risk prediction of patients undergoing percutaneous coronary intervention (PCI). METHODS: In this population-based cohort study, a total of 46 features, including patient clinical and coronary lesion characteristics, were assessed for analysis through machine learning models. The ACEF-QFR scoring system was developed using 1263 consecutive cases of CAD patients after PCI in PANDA III trial database. The newly developed score was then validated on the other remaining 542 patients in the cohort. RESULTS: In both the Random Forest Model and the DeepSurv Model, age, renal function (creatinine), cardiac function (LVEF) and post-PCI coronary physiological index (QFR) were identified and confirmed to be significant predictive factors for 2-year adverse cardiac events. The ACEF-QFR score was constructed based on the developmental dataset and computed as age (years)/EF (%) + 1 (if creatinine ≥ 2.0 mg/dL) + 1 (if post-PCI QFR ≤ 0.92). The performance of the ACEF-QFR scoring system was preliminarily evaluated in the developmental dataset, and then further explored in the validation dataset. The ACEF-QFR score showed superior discrimination (C-statistic = 0.651; 95% CI: 0.611-0.691, P < 0.05 versus post-PCI physiological index and other commonly used risk scores) and excellent calibration (Hosmer-Lemeshow χ2 = 7.070; P = 0.529) for predicting 2-year patient-oriented composite endpoint (POCE). The good prognostic value of the ACEF-QFR score was further validated by multivariable Cox regression and Kaplan-Meier analysis (adjusted HR = 1.89; 95% CI: 1.18-3.04; log-rank P < 0.01) after stratified the patients into high-risk group and low-risk group. CONCLUSIONS: An improved scoring system combining clinical and coronary lesion-based functional variables (ACEF-QFR) was developed, and its ability for prognostic prediction in patients with PCI was further validated to be significantly better than the post-PCI physiological index and other commonly used risk scores.

Diagnostic performance of ultrasonic flow ratio versus quantitative flow ratio for assessment of coronary stenosis.

BACKGROUND: Ultrasonic flow ratio (UFR) is a novel intravascular ultrasound (IVUS)-derived modality for fast computation of fractional flow reserve (FFR) without pressure wires and adenosine. AIMS: This study was sought to compare the diagnostic performance of UFR and quantitative flow ratio (QFR), using FFR as the reference standard. METHODS: This is a retrospective study enrolling consecutive patients with intermediate coronary artery lesions (diameter stenosis of 30%-90% by visual estimation) for IVUS and FFR measurement. UFR and QFR were performed offline in a core-lab by independent analysts blinded to FFR. RESULTS: From December 2022 to May 2023, a total of 78 eligible patients were enrolled. IVUS and FFR measurements were successfully conducted in 104 vessels, finally 98 vessels with both FFR, UFR and QFR evaluation were analyzed. Mean FFR was 0.79 ± 0.12. UFR showed a strong correlation with FFR similar to QFR (r = 0.83 vs. 0.82, p = 0.795). Diagnostic accuracy of UFR was non-inferior to QFR (94% [89%-97%] versus 90% [84%-94%], p = 0.113). Sensitivity and specificity in identifying hemodynamically significant stenosis were comparable between UFR and QFR (sensitivity: 89% [79%-96%] versus 85% [74%-92%], p = 0.453; specificity: 97% [91%-99%] versus 95% [88%-99%], p = 0.625). The area under curve for UFR was 0.95 [0.90-0.98], non-inferior to QFR (difference = 0.021, p = 0.293), and significantly higher than minimum lumen area (MLA; difference = 0.13, p < 0.001). Diagnostic accuracy of UFR and QFR was not statically different in bifurcation nor non-bifurcation lesions. CONCLUSIONS: UFR showed excellent concordance with FFR, non-inferior to QFR, superior to MLA. UFR provides a potentiality for the integration of physiological assessment and intravascular imaging in clinical practice.