Leucine Supplementation Modulates Lipid Metabolism and Inflammation in Early Weaning Piglets.

Early weaning can induce the programmed dysregulation of glycolipid metabolism and inflammation in adult animals. The primary objective of this study was to evaluate the efficacy of leucine supplementation administered promptly after early weaning in mitigating these adverse effects in piglets. At day 21, 24 piglets were randomly selected and divided into 3 groups: EW group where the piglets were weaned at day 21 and fed basal diet, EWL group where the piglets were weaned at day 21 and fed the basal diet with supplementation of 1% leucine, and C group where the piglets were fed basal diet and weaned at 28 days. Each group contained eight replicates, with one piglet per replicate. The results indicated that early weaning had an impact on gut health and could activate the inhibitor of the kappa B kinase gamma/inhibitor kappa B alpha/NF-kappa-B (IKKγ/IκBα/NF-κB) signaling pathway to ameliorate pro-inflammatory factor and apoptosis levels. Furthermore, early weaning reduced the activity of fatty acid ß oxidation (FAßO) and affected genes linked with lipid metabolism. Supplementing with leucine can improve the effects of these factors. In summary, leucine may alleviate the influences of early weaning on the lipid metabolism and inflammation in piglets.

Efficient intersystem crossing and tunable ultralong organic room-temperature phosphorescence via doping polyvinylpyrrolidone with polyaromatic hydrocarbons.

Polymer-based pure organic room-temperature phosphorescent materials have tremendous advantages in applications owing to their low cost, vast resources, and easy processability. However, designing polymer-based room-temperature phosphorescent materials with large Stokes shifts as key requirements in biocompatibility and environmental-friendly performance is still challenging. By generating charge transfer states as the gangplank from singlet excited states to triplet states in doped organic molecules, we find a host molecule (pyrrolidone) that affords charge transfer with doped guest molecules, and excellent polymer-based organic room-temperature phosphorescent materials can be easily fabricated when polymerizing the host molecule. By adding polyaromatic hydrocarbon molecules as electron-donor in polyvinylpyrrolidone, efficient intersystem crossing and tunable phosphorescent from green to near-infrared can be achieved, with maximum phosphorescence wavelength and lifetime up to 757 nm and 3850 ms, respectively. These doped polyvinylpyrrolidone materials have good photoactivation properties, recyclability, advanced data encryption, and anti-counterfeiting. This reported design strategy paves the way for the design of polyvinylpyrrolidone-based room-temperature phosphorescent materials.

Morphological quality on Day 3 affects the pregnancy outcomes of low-quality euploid blastocysts: a retrospective cohort study.

STUDY QUESTION: Does the morphological quality on Day 3 influence the pregnancy outcomes of euploid blastocysts? SUMMARY ANSWER: The morphological quality on Day 3 affects the clinical pregnancy rate (CPR) and live birth rate (LBR) of low-quality euploid blastocysts. WHAT IS KNOWN ALREADY: The morphological grading of Day 3 embryos affects the pregnancy outcome of cleavage-stage embryos and is an excellent indicator to predict embryo development potential. However, it is still unclear whether morphological quality on Day 3 is associated with pregnancy outcomes of the euploid blastocyst. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study comprised 1275 patients who received single euploid blastocyst transfer between January 2016 and August 2021 at a tertiary teaching hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were grouped into two groups according to the morphological grading on Day 3 of transferred blastocysts: high-quality (HQ, including Grades I and II) Day 3 embryos and low-quality (LQ, Grade III) Day 3 embryos. The primary outcomes were CPR and LBR. Interactions of development days (Day 5 and Day 6) and morphological quality (high- and low-quality) of blastocysts with morphological quality of Day 3 embryos on pregnancy outcomes were tested in the stratified analysis and logistic regression models. The multivariate logistic regression analysis was conducted to investigate the independent effect of the morphological quality of Day 3 embryos on pregnancy outcomes after adjusting for potentially confounding factors. MAIN RESULTS AND THE ROLE OF CHANCE: The CPR and LBR of the HQ Day 3 embryos group were statistically higher than those of the LQ Day 3 embryos group (CPR: 59.73% versus 49.70%, respectively, P = 0.015; LBR: 49.73% versus 41.21%, respectively, P = 0.041). The development days of blastocysts did not exhibit a multiplicative interaction with the morphological quality of Day 3 embryos on the CPR (P for interaction = 0.648) and LBR (P for interaction = 0.925). The morphological quality of blastocysts exhibits a multiplicative interaction with the morphological quality of Day 3 embryos on the CPR (P for interaction = 0.020) and LBR (P for interaction = 0.012). After adjusting for potential confounders, the HQ Day 3 embryo group was positively associated with the CPR (adjusted odds ratio (aOR): 2.10, 95% CI: 1.31-3.36, P = 0.002) and LBR (aOR: 1.97, 95% CI: 1.20-3.25, P = 0.008) of LQ blastocysts. However, the morphological quality on Day 3 was not significantly associated with the CPR (aOR: 0.95, 95% CI: 0.58-1.55, P = 0.835) and LBR (aOR: 0.86, 95% CI: 0.53-1.40, P = 0.550) of HQ blastocysts. LIMITATIONS, REASONS FOR CAUTION: Selection and confounding bias introduced by the retrospective design cannot be completely eliminated in this study, although multivariable logistic analysis was conducted to adjust for potential confounders. Also, some subgroups had small sample sizes, which may reduce statistical power. Moreover, participants in our study only received single euploid blastocyst transfer, and whether the results could apply to blastocysts with unknown ploidy status is unclear. WIDER IMPLICATIONS OF THE FINDINGS: This study found that the morphological quality on Day 3 was significantly associated with the CPR and LBR of LQ blastocysts; Therefore, when only LQ euploid blastocysts are available for transfer, blastocysts derived from HQ Day 3 embryos are recommended. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Research and Development of a Big Data Application Platform for Intelligent Blast Furnace Intensive Management and Control.

The blast furnaces of Anshan Iron and Steel have completed large-scale modernization, and a large amount of information technology has been popularized and applied to the process of blast furnaces. This paper takes the Anshan Iron and Steel blast furnace group as the research background. Based on big data and industrial Internet technology, combining the smelting process mechanism of blast furnace production and using artificial intelligence, cloud analysis, and other technologies, the data management platform was used to effectively integrate the data of each process of the blast furnace and design the data asset catalogue. The big data application platform for the intensive control of the blast furnace was established. The data were in multidimensional in-depth mining, and the intelligent application model of the blast furnace was established. The visual intelligent monitoring of the safe production and operation of the blast furnace was realized, and the production operation of the blast furnace was guided. The overall information and intelligent level of production operation and management of the blast furnace have been improved.

Inoculation with Funneliformis mosseae promotes selenium accumulation and transformation in pepper (Capsicum annuum L.).

Selenium (Se) is one of the fifteen essential nutrients required by the human body. Mycorrhizal microorganisms play a crucial role in enhancing selenium availability in plants. However, limited research exists on the impact of arbuscular mycorrhizal fungi (AMF) on selenium accumulation and transport in pepper plants. This study employed a pot experiment to investigate the changes in pepper plant growth, selenium accumulation, and transformation following inoculation with AMF and varying concentrations of exogenous selenium. The results indicate that exogenous selenium application in pepper has dual effects. At low concentrations (≤8 mg L⁻1), it promotes growth and nutrient accumulation, whereas high concentrations (>16 mg L⁻1) inhibit these processes. AMF inoculation positively influences selenium accumulation and transport in peppers, significantly increasing yield per plant by 17.89%, vitamin C content by 67.36%, flavonoid content by 43.26%, capsaicin content by 14.82%, DPPH radical scavenging rate by 18.18%, and ABTS radical scavenging rate by 27.81%. Additionally, it significantly reduces selenocysteine methyltransferase (SMT) enzyme activity, while minimally affecting ATP sulfurylase (ATPS) and adenosyl sulfate reductase (APR) enzyme activities. The combined treatment of AMF and 8 mg L⁻1 exogenous selenium has been proven to be the most effective for selenium enrichment in peppers, offering new insights into utilizing exogenous selenium and AMF inoculation to enhance selenium content in peppers.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

BoaBZR1.1 mediates brassinosteroid-induced carotenoid biosynthesis in Chinese kale.

Brassinazole resistant 1 (BZR1), a brassinosteroid (BR) signaling component, plays a pivotal role in regulating numerous specific developmental processes. Our study demonstrated that exogenous treatment with 2,4-epibrassinolide (EBR) significantly enhanced the accumulation of carotenoids and chlorophylls in Chinese kale (Brassica oleracea var. alboglabra). The underlying mechanism was deciphered through yeast one-hybrid (Y1H) and dual-luciferase (LUC) assays, whereby BoaBZR1.1 directly interacts with the promoters of BoaCRTISO and BoaPSY2, activating their expression. This effect was further validated through overexpression of BoaBZR1.1 in Chinese kale calli and plants, both of which exhibited increased carotenoid accumulation. Additionally, qPCR analysis unveiled upregulation of carotenoid and chlorophyll biosynthetic genes in the T1 generation of BoaBZR1.1-overexpressing plants. These findings underscored the significance of BoaBZR1.1-mediated BR signaling in regulating carotenoid accumulation in Chinese kale and suggested the potential for enhancing the nutritional quality of Chinese kale through genetic engineering of BoaBZR1.1.

Application of indocyanine green fluorescence imaging in hepatobiliary surgery.

Indocyanine green (ICG) is a fluorescent dye with an emission wavelength of about 840 nm, which is selectively absorbed by the liver after intravenous or bile duct injection, and then it is excreted into the intestines through the biliary system. With the rapid development of fluorescence laparoscopy, ICG fluorescence imaging is safe, feasible, and widely used in hepatobiliary surgery. ICG fluorescence imaging is of great significance in precise preoperative and intraoperative localization of liver lesions, real-time visualization of hepatic segmental anatomy, intrahepatic and extrahepatic biliary tract visualization, and liver transplantation. ICG fluorescence imaging facilitates efficient intraoperative hepatobiliary decision-making and improves the safety of minimally invasive hepatobiliary surgery. Advances in imaging systems will increase the use of fluorescence imaging as an intraoperative navigation tool, improving the safety and accuracy of open and laparoscopic/robotic hepatobiliary surgery. Herin, we have reviewed the status of ICG applications in hepatobiliary surgery, aiming to provide new insights for the development of hepatobiliary surgery.

Oxidative phosphorylation regulates B cell effector cytokines and promotes inflammation in multiple sclerosis.

Dysregulated B cell cytokine production contributes to pathogenesis of immune-mediated diseases including multiple sclerosis (MS); however, the underlying mechanisms are poorly understood. In this study we investigated how cytokine secretion by pro-inflammatory (GM-CSF-expressing) and anti-inflammatory (IL-10-expressing) B cells is regulated. Pro-inflammatory human B cells required increased oxidative phosphorylation (OXPHOS) compared with anti-inflammatory B cells. OXPHOS reciprocally modulated pro- and anti-inflammatory B cell cytokines through regulation of adenosine triphosphate (ATP) signaling. Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a "fourth signal" that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases.

Sorafenib plus TACE with or without camrelizumab for the treatment of intermediate and advanced hepatocellular carcinoma.

OBJECTIVES: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and camrelizumab or with sorafenib alone in patients with intermediate or advanced hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed 78 patients with intermediate or advanced HCC who were treated at our centers between January 2018 and December 2021. 26 of them received sorafenib and camrelizumab plus TACE (the TACE + Sor + C group), while 52 received TACE and sorafenib (the TACE + Sor group). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. RESULTS: The mOS (22 vs. 10 months, P < 0.001) and mPFS (11 vs. 6 months, P = 0.008) of the TACE + Sor + C group were significantly higher than those of the TACE + Sor group. Multivariate analysis showed that compared with TACE + Sor + C, TACE + Sor increased the risk of all-cause mortality and tumor progression. For grade I and II adverse events (AEs), the incidence of skin capillary hyperplasia and hypothyroidism in the TACE + Sor + C group was significantly higher than that in the TACE + Sor group. For serious AEs (grade III or IV), there was no significant difference in any adverse reaction between the two groups (P > 0.05). CONCLUSION: Patients with intermediate or advanced HCC appeared to benefit more in terms of survival from TACE + Sor + C than from TACE + Sor, and the AEs were tolerable. ADVANCES IN KNOWLEDGE: 1.Subgroup analysis demonstrated TACE+ Sorafenib+ Camrelizumab could benefit HCC patients regardless of whether they had PVTT, BCLC B or C, or CHILD A or B；2.We reported the immunotherapy related adverse events (irAEs) occurred with a significant higher incidence in triple treatment, but all the adverse events are tolerable.

Magnaporthe oryzae infection triggers rice resistance to brown planthopper through the influence of jasmonic acid on the flavonoid biosynthesis pathway.

In agroecosystems, plants are constantly exposed to attack from diverse herbivorous insects and microbes, and infestation with one species may change the plant defense response to other species. In our investigation of the relationships among rice plants, the brown planthopper Nilaparvata lugens (Stål) and the rice blast fungus Magnaporthe oryzae, we observed a significant increase in the resistance of rice treated with rice blast to N. lugens, as evidenced by improved plant survival rates in a small population resistance study. Subsequent transcriptome data analysis revealed that the rice blast fungus can induce the expression of genes in the jasmonic acid (JA) and flavonoid pathways. Similar to the flavonoid pathway, the JA pathway also contains 2 types of genes that exhibit similar and opposite trends in response to N. lugens and rice blast. Among these genes, the osjaz1 mutant and the osmyc2 mutant were phenotypically confirmed to positively and negatively regulate rice resistance to N. lugens and rice blast, respectively. Subsequent mass spectrometry and quantification experiments showed that the exogenous application of methyl jasmonate (MeJA) can induce the accumulation of eriodictyol, naringenin and quercetin, as well as the expression of OsF3H, Os4CL5 and OsCHI in the flavonoid pathway. This suggests a close connection between the JA pathway and the flavonoid pathway. However, OsF3'H, which negatively regulates rice resistance to N. lugens and rice blast, did not show increased expression. Phenotypic and molecular experiments confirmed that OsMYC2 can bind to and inhibit the expression of OsF3'H, thus revealing the mechanism of rice resistance to N. lugens after treatment with rice blast. These findings will deepen our understanding of the interactions among rice, N. lugens and rice blast.

Chlorogenic acid improves the development of porcine parthenogenetic embryos by regulating oxidative stress and ameliorating mitochondrial function.

Chlorogenic acid (CGA) is an effective phenolic antioxidant that can scavenge hydroxyl radicals and superoxide anions. Herein, the protective effects and mechanisms leading to CGA-induced porcine parthenogenetic activation (PA) in early-stage embryos were investigated. Our results showed that 50 µM CGA treatment during the in vitro culture (IVC) period significantly increased the cleavage and blastocyst formation rates and improved the blastocyst quality of porcine early-stage embryos derived from PAs. Then, genes related to zygotic genome activation (ZGA) were identified and investigated, revealing that CGA can promote ZGA in porcine PA early-stage embryos. Further analysis revealed that CGA treatment during the IVC period decreased the abundance of reactive oxygen species (ROS), increased the abundance of glutathione and enhanced the activity of catalase and superoxide dismutase in porcine PA early-stage embryos. Mitochondrial function analysis revealed that CGA increased mitochondrial membrane potential and ATP levels and upregulated the mitochondrial homeostasis-related gene NRF-1 in porcine PA early-stage embryos. In summary, our results suggest that CGA treatment during the IVC period helps porcine PA early-stage embryos by regulating oxidative stress and improving mitochondrial function.

Photocatalytic degradation of p-aminobenzoic acid on N-biomass charcoal etched with Fe-Al-bilayer hydroxide: New insights through spectroscopic investigation.

We investigated the photocatalytic property of etched iron­aluminum layered double hydroxide (LDH) composites using urea-modified biochar (N-BC) carrier to degrade para-aminobenzoic acid (PABA), a refractory organic pollutant. The prepared FeAl-LDH@FeSx-N-BC composite exhibited excellent photocatalytic performance, attributed to the enhanced photogenerated charge-carrier separation by the etched LDH and the improved comparative surface areas by the doped N-BC. The composite photocatalytically degraded 96 % of PABA. The performance was affected by solute concentration, pH and photocatalyst dose. Adding p-benzoquinone and EDTA-2Na significantly decreased the degradation rate, suggesting that superoxide radicals and holes were co-involved in PABA degradation. The excellent PABA removal efficiency was consistent for three consecutive runs. The samples' reactive oxygen species was confirmed, as electron paramagnetic reverberation explained the photodegradation mechanism. Under xenon lamp irradiation, two PABA photocatalytic degradation pathways were proposed using Liquid Chromatograph Mass Spectrometer (LCMS) and density functional theory. As expected, FeAl-LDH@FeSx-N-BC showed excellent photocatalytic performance, expanding a new direction and possibility for future photocatalytic treatment of water pollutants.

Predictability of B cell clonal persistence and immunosurveillance in breast cancer.

B cells and T cells are important components of the adaptive immune system and mediate anticancer immunity. The T cell landscape in cancer is well characterized, but the contribution of B cells to anticancer immunosurveillance is less well explored. Here we show an integrative analysis of the B cell and T cell receptor repertoire from individuals with metastatic breast cancer and individuals with early breast cancer during neoadjuvant therapy. Using immune receptor, RNA and whole-exome sequencing, we show that both B cell and T cell responses seem to coevolve with the metastatic cancer genomes and mirror tumor mutational and neoantigen architecture. B cell clones associated with metastatic immunosurveillance and temporal persistence were more expanded and distinct from site-specific clones. B cell clonal immunosurveillance and temporal persistence are predictable from the clonal structure, with higher-centrality B cell antigen receptors more likely to be detected across multiple metastases or across time. This predictability was generalizable across other immune-mediated disorders. This work lays a foundation for prioritizing antibody sequences for therapeutic targeting in cancer.

Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: We performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Compared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688-0.823), 0.758 (95% CI: 0.687-0.821), 0.714 (95% CI: 0.639-0.781), 0.709 (95% CI: 0.634-0.777), 0.723 (95% CI: 0.649-0.789), and 0.728 (95% CI: 0.654-0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499-0.653) and 0.694 (95% CI: 0.619-0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790-0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015). CONCLUSION: Our study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.

Pregnancy outcomes in women with primary ovarian insufficiency in assisted reproductive technology therapy: a retrospective study.

Purpose: This study aims to retrospectively estimate cumulative reproductive outcomes in women with primary ovarian insufficiency (POI) in assisted reproductive technology (ART) therapy. Methods: A total of 139 patients diagnosed with POI were reviewed in this study. Firstly, they were divided into two groups according to oocyte origin: using their own oocytes (OG group) or accepting oocyte donations (OD I group). Secondly, the patients were split depending on the pregnancy outcome. In the OG group, nine patients decided to use others' oocytes after a failure of attempting to use their own, and this population was the oocyte donation II group (OD II group). Results: There were 88 patients who used their own oocytes, while 51 patients accepted oocyte donations. In the OG group, there are only 10 (7.2%) patients who got pregnant, and patients in the OD group had worse hormone levels (FSH 71.37 ± 4.18 vs. 43.98 ± 2.53, AMH 0.06 ± 0.04 vs. 1.15 ± 0.15, and AFC 0.10 ± 0.06 vs. 1.15 ± 0.15) and more years of infertility (5.04 ± 0.48 vs. 3.82 ± 0.30), which explained why they choose oocyte donation. In all the three groups, baseline characteristics were comparable between pregnant women and non-pregnant women. Of the 10 pregnant patients in the OG group, four of them used luteal-phase short-acting long protocol and had pregnancies successfully in their first cycles. Conclusion: Ovarian stimulation in POI women requires more cost and time. For those with a stronger desire to have genetic offspring, luteal-phase short-acting long protocol may help them obtain pregnancy rapidly.

Long-term PM2.5 exposure associated with severity of angina pectoris and related health status in patients admitted with acute coronary syndrome: Modification effect of genetic susceptibility and disease history.

Long-term particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) exposure has been associated with the occurrence of acute coronary syndrome (ACS). However, the impact of PM2.5 exposure and its components on the severity of angina pectoris and disease-related health status in patients hospitalized for ACS is understudied. To assess the association between long-term exposure to PM2.5 components and the angina pectoris severity in ACS patients, as well as the modification effects of genetic factors and disease history in north China. During 2017-2019, 6729 ACS patients were collected in Shandong Province and Beijing, with their angina pectoris severity evaluated using Seattle Angina Questionnaire (SAQ). The 0-3 years' average concentrations of PM2.5 and its five major components were assigned to each patient's residential address. Linear mixed-effects model, weighted quantile regression, and quantile g-computation were used to estimate the effects of both single and joint associations between PM2.5 components and SAQ scores. The interactive effect was estimated by polygenic risk scores and disease history. For each interquartile range increase in PM2.5, the overall SAQ score changed by -3.71% (95%CI: -4.54% to -2.88%), with score of angina stability more affected than angina frequency and other dimensions of angina pectoris severity. Sulfate and ammonium were major contributors to the effect of PM2.5 exposure. Significant modification effect was only observed for disease history, especially for the dimension of physical limitation. Among a series of pre-existing diseases, patients with a family history of coronary artery disease, previous percutaneous coronary intervention or coronary artery bypass grafting, and stroke were more susceptible to PM2.5 exposure than others. Greater exposure to PM2.5 is associated with more serious angina pectoris and worse disease-related health status in ACS patients. Public health and clinical priority should be given to cutting down key effective components and protecting highly vulnerable individuals.

Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway.

Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD+ synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM NR also effectively increased the viability and decreased the LDH release of H9c2 cells during OGD/R. We had provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD+ content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we had confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested that exogenous supplementation with NR mitigated mitochondrial damage and inhibited apoptosis during myocardial I/R injury by reducing mitochondrial oxidative stress via SIRT3-SOD2-mtROS pathway.