Shizukaol C alleviates trimethylamine oxide-induced inflammation through activating Keap1-Nrf2-GSTpi pathway in vascular smooth muscle cell.

BACKGROUND: Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation. PURPOSE: The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation. METHODS: The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo, TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay. RESULTS: Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation. CONCLUSION: Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB/p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo, suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases.

Triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio predict the prognosis in patients with type B aortic dissection receiving thoracic endovascular aortic repair.

Background: The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio are both reliable surrogate indicator of insulin resistance and have been shown to be valuable in predicting various cardiovascular diseases. However, few studies have explored its association with the prognosis of type B aortic dissection (TBAD) patients receiving thoracic endovascular aortic repair (TEVAR). Methods: A total of 1,425 consecutive patients who underwent TEVAR were included. Data from 935 patients were analyzed in the study. The endpoint was defined as 30-day and 1-year aortic-related adverse events (ARAEs), all-cause mortality, and major adverse cardiovascular and cerebrovascular events (MACCEs). Results: There were 935 patients included during a mean follow-up time of 2.8 years. After adjusting for multiple confounding factors, continuous TG/HDL-c [hazard ratio (HR) =1.07; 95% confidence interval (CI): 1.00-1.15; P=0.041] was independently associated with 1-year all-cause mortality. Both a high (Quintile 5: TG/HDL-c ratio ≥4.11) (HR =4.84; 95% CI: 1.55-15.13; P=0.007) and low TG/HDL-c ratio (Quintile 1: TG/HDL-c ratio <1.44) (HR =4.67; 95% CI: 1.46-14.94; P=0.001) were still independent risk factors for 1-year all-cause mortality. Conclusions: Elevated baseline TG/HDL-c ratio and TG/HDL-c ≥4.11 were significantly related to a higher risk of 1-year all-cause mortality among TBAD patients undergoing TEVAR. At the same time, the low TG/HDL-c ratio was also independently associated with 1-year all-cause mortality. Special attention should be paid to TBAD patients with a higher or an overly low TG/HDL-c ratio.

Roxadustat reduces left ventricular mass index compared to rHuEPO in haemodialysis patients in a randomized controlled trial.

BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in haemodialysis (HD) patients and is associated with an increased risk of death. Roxadustat and recombinant human erythropoietin (rHuEPO, abbreviated as EPO) are the main treatment strategies for renal anaemia in HD patients, but it has not been clear whether there is a difference in their effect on LVH. METHODS: In this multi-centre, prospective, randomized trial of 12-month duration, study participants were randomized in a 1:1 ratio to the roxadustat group or the EPO group. The doses of both treatment regimens were adjusted so that the patients had a haemoglobin level of 10.0-12.0 g per dL. The primary study endpoint was the change from baseline to 12 months in the left ventricular mass index (LVMI, g/m2) measured by echocardiography. RESULTS: In total, 114 patients were enrolled. The mean age was 50 years, and the median dialysis duration was 33 months. Sixty-one patients were men, and 24 were diabetic. LVMI decreased from 116.18 ± 27.84 to 110.70 ± 25.74 g/m2 in the roxadustat group. However, it increased from 109.35 ± 23.41 to 114.99 ± 28.46 g/m2 in the EPO group, with a significant difference in the change in LVMI between the two groups [-5.48 (-11.60 to 0.65) vs. 5.65 (0.74 to 10.55), p < 0.05]. Changes in left ventricular mass, end-diastolic volume and 6-min walk test seemed superior in the roxadustat group. There were no significant differences in other cardiac geometry, biochemical parameters and major adverse cardiovascular events between the two groups. CONCLUSIONS: Compared to EPO, roxadustat is more helpful in the regression of LVH in HD patients.

Fine mapping of ClLOX, a QTL for powdery mildew resistance in watermelon (Citrullus lanatus L.).

KEY MESSAGE: ClLOX, is located on chromosome 2 and encodes a lipoxygenase gene, which induced watermelon powdery mildew resistance by inhibiting pathogen spread. Powdery mildew is one of the most severe fungal diseases reducing yield and quality of watermelon (Citrullus lanatus L.) and other cucurbit crops. Genes responsible for powdery mildew resistance in watermelon are highly valuable. In this study, we first identified the QTL pm-lox for powdery mildew resistance in watermelon, located within a 0.93 Mb interval of chromosome 2, via XP-GWAS method using two F2 populations. The F2:3 families from one of the F2 populations were then used for fine-mapping the pm-lox locus into a 9,883 bp physical region between 29,581,906 and 29,591,789, containing only two annotated genes. Of these, only ClG42_02g0161300 showed a significant differential expression between the resistant and susceptible lines after powdery mildew inoculation based on RNA sequencing (RNA-seq) and qRT-PCR analysis, and is designated ClLOX. Derived Cleaved Amplified Polymorphic Sequence (dCAPs) markers were developed and validated. In addition, our tests showed that the resistance was anti-spread rather than anti-infection of the pathogen. This study identified a new resistance gene (ClLOX), provided insights into the mechanism of powdery mildew resistance, and developed a molecular marker for watermelon breeding.

Methionine availability influences essential H3K36me3 dynamics during cell differentiation.

Histone modifications are integral to epigenetics through their influence on gene expression and cellular status. While it's established that metabolism, including methionine metabolism, can impact histone methylation, the direct influence of methionine availability on crucial histone marks that determine the epigenomic process remains poorly understood. In this study, we demonstrate that methionine, through its metabolic product, S-adenosylmethionine (SAM), dynamically regulates H3K36me3, a cancer-associated histone modification known to influence cellular status, and myogenic differentiation of mouse myoblast cells. We further demonstrate that the methionine-dependent effects on differentiation are mediated in part through the histone methyltransferase SETD2. Methionine restriction leads to preferential decreases in H3K36me3 abundance and genome accessibility of genes involved in myogenic differentiation. Importantly, the effects of methionine restriction on differentiation and chromatin accessibility can be phenocopied by the deletion of Setd2. Collectively, this study demonstrates that methionine metabolism through its ability to be sensed by chromatin modifying enzymes can have a direct role in influencing cell fate determination.

Ferroptosis: A potential target of macrophages in plaque vulnerability.

Plaque vulnerability has been the subject of several recent studies aimed at reducing the risk of stroke and carotid artery stenosis. Atherosclerotic plaque development is a complex process involving inflammation mediated by macrophages. Plaques become more vulnerable when the equilibrium between macrophage recruitment and clearance is disturbed. Lipoperoxides, which are affected by iron levels in cells, are responsible for the cell death seen in ferroptosis. Ferroptosis results from lipoperoxide-induced mitochondrial membrane toxicity. Atherosclerosis in ApoE(-/-) mice is reduced when ferroptosis is inhibited and iron intake is limited. Single-cell sequencing revealed that a ferroptosis-related gene was substantially expressed in atherosclerosis-modeled macrophages. Since ferroptosis can be regulated, it offers hope as a non-invasive method of treating carotid plaque. In this study, we discuss the role of ferroptosis in atherosclerotic plaque vulnerability, including its mechanism, regulation, and potential future research directions.

The Versatile Biocatalyst of Cytochrome P450 CYP102A1: Structure, Function, and Engineering.

Wild-type cytochrome P450 CYP102A1 from Bacillus megaterium is a highly efficient monooxygenase for the oxidation of long-chain fatty acids. The unique features of CYP102A1, such as high catalytic activity, expression yield, regio- and stereoselectivity, and self-sufficiency in electron transfer as a fusion protein, afford the requirements for an ideal biocatalyst. In the past three decades, remarkable progress has been made in engineering CYP102A1 for applications in drug discovery, biosynthesis, and biotechnology. The repertoire of engineered CYP102A1 variants has grown tremendously, whereas the substrate repertoire is avalanched to encompass alkanes, alkenes, aromatics, organic solvents, pharmaceuticals, drugs, and many more. In this article, we highlight the major advances in the past five years in our understanding of the structure and function of CYP102A1 and the methodologies used to engineer CYP102A1 for novel applications. The objective is to provide a succinct review of the latest developments with reference to the body of CYP102A1-related literature.

Senkyunolide I ameliorates thoracic aortic aneurysm and dissection in mice via inhibiting the oxidative stress and apoptosis of endothelial cells.

BACKGROUND: Thoracic aortic aneurysm and aortic dissection (TAAD) is one of the most fatal cardiovascular diseases. Senkyunolide I (SEI) is a component of traditional Chinese medicine with remarkable anti-inflammatory properties and exhibits remarkable protective effects, but its impact on TAAD remains unclear. Our study aimed to explore the role of SEI in a murine model of TAAD and further explore the immunopharmacological mechanism. METHODS AND MATERIALS: The in vivo model were assessed using echocardiography, gross anatomy, and tissue staining. Western blot and immunofluorescence were performed to evaluate the effects of SEI in vivo and in vitro. A SEI solution injection containing 1 % dimethyl sulfoxide (DMSO) was administered intraperitoneally to the TAAD model group, while a normal saline injection comprising 1 % DMSO was administered to the sham group. RESULTS: SEI prevented TAAD formation induced by BAPN/Ang II and reduced the TAAD incidence in mice. SEI treatment significantly inhibited the degradation of collagen and elastin fibers in the extracellular matrix. Furthermore, it reduced the expression of inflammatory factors in the aortic intima. Western blot analysis revealed that SEI-treated mice showed a significant decrease in apoptosis-related protein levels in the aorta compared with the TAAD group. PI3K, Akt, and mTOR in the SEI treatment group were significantly lower than in the model group. SEI could also attenuate H2O2-induced Human umbilical vein endothelial cells (HUVECs) damage and reverse the decline in migrant cells. The apoptosis of HUVECs was considerably reduced by the SEI treatment. CONCLUSIONS: Conclusively, SEI may alleviate the progression of TAAD by suppressing the PI3K/Akt/NF-κB signaling pathway. The SEI's ability to inhibit inflammation and oxidative stress opens the way to restore the function of endothelial cells and vascular homeostasis, and thus to provide novel and promising options for the treatment of TAAD patients.

Computational redesign of cytochrome P450 CYP102A1 for highly stereoselective omeprazole hydroxylation by UniDesign.

Cytochrome P450 CYP102A1 is a prototypic biocatalyst that has great potential in chemical synthesis, drug discovery, and biotechnology. CYP102A1 variants engineered by directed evolution and/or rational design are capable of catalyzing the oxidation of a wide range of organic compounds. However, it is difficult to foresee the outcome of engineering CYP102A1 for a compound of interest. Here, we introduce UniDesign as a computational framework for enzyme design and engineering. We tested UniDesign by redesigning CYP102A1 for stereoselective metabolism of omeprazole (OMP), a proton pump inhibitor, starting from an active but nonstereoselective triple mutant (TM: A82F/F87V/L188Q). To shift stereoselectivity toward (R)-OMP, we computationally scanned three active site positions (75, 264, and 328) for mutations that would stabilize the binding of the transition state of (R)-OMP while destabilizing that of (S)-OMP and picked three variants, namely UD1 (TM/L75I), UD2 (TM/A264G), and UD3 (TM/A328V), for experimentation, based on computed energy scores and models. UD1, UD2, and UD3 exhibit high turnover rates of 55 ± 4.7, 84 ± 4.8, and 79 ± 5.7 min-1, respectively, for (R)-OMP hydroxylation, whereas the corresponding rates for (S)-OMP are only 2.2 ± 0.19, 6.0 ± 0.68, and 14 ± 2.8 min-1, yielding an enantiomeric excess value of 92, 87, and 70%, respectively. These results suggest the critical roles of L75I, A264G, and A328V in steering OMP in the optimal orientation for stereoselective oxidation and demonstrate the utility of UniDesign for engineering CYP102A1 to produce drug metabolites of interest. The results are discussed in the context of protein structures.

Physiological and transcriptomic analysis of a yellow leaf mutant in watermelon.

Leaf color mutants are important materials for studying chloroplast and photomorphogenesis, and can function as basic germplasms for genetic breeding. In an ethylmethanesulfonate mutagenesis population of watermelon cultivar "703", a chlorophyll-deficient mutant with yellow leaf (Yl2) color was identified. The contents of chlorophyll a, chlorophyll b, and carotenoids in Yl2 leaves were lower than those in wild-type (WT) leaves. The chloroplast ultrastructure in the leaves revealed that the chloroplasts in Yl2 were degraded. The numbers of chloroplasts and thylakoids in the Yl2 mutant were lower, resulting in lower photosynthetic parameters. Transcriptomic analysis identified 1292 differentially expressed genes, including1002 upregulated and 290 downregulated genes. The genes involved in chlorophyll biosynthesis (HEMA, HEMD, CHL1, CHLM, and CAO) were significantly downregulated in the Yl2 mutant, which may explain why chlorophyll pigment content was lower than that in the WT. Chlorophyll metabolism genes such as PDS, ZDS and VDE, were upregulated, which form the xanthophyll cycle and may protect the yellow‒leaves plants from photodamage. Taken together, our findings provide insight into the molecular mechanisms of leading to leaf color formation and chloroplast development in watermelon.

Exosomal lncRNA GAS5 promotes M1 macrophage polarization in allergic rhinitis via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling.

Macrophages are involved in the pathogenesis of allergic rhinitis (AR), but how these macrophages are polarized to M1 or M2 type is undetermined. Long non-coding RNA growth arrest specific transcript 5 (GAS5) is upregulated in exosomes isolated from nasal mucus of AR patients (AR-EXO) and aggravates nasal symptoms in AR mice. In the present study, we are aimed to elucidate the potential role of GAS5 in macrophage polarization during AR pathogenesis. An AR mice model was constructed. The potential function of GAS5 was evaluated by western blot, RNA immunoprecipitation (RIP), biotinylated RNA pull-down assay, co-immunoprecipitation (co-IP) assay, flow cytometry, enzyme-linked immunosorbent assay (ELISA) assay, and immunohistochemistry (IHC) staining. We found that GAS5 is upregulated in ovalbumin-treated human nasal epithelial cells RPMI 2650 (OVA-EXO) and nasal mucus of AR mice. OVA-EXO treatment or forced GAS5 expression promoted M1 macrophage polarization of peripheral blood monocytes (PB monocytes) and THP-1 macrophages in vitro. GAS5 overexpression aggravated the allergic nasal symptoms induced by OVA in AR mice and facilitated M1 macrophage polarization and allergic inflammation, while knockdown of GAS5 exhibited opposite effects in vivo. GAS5 activated NF-кB signaling via suppressing autophagy-dependent degradation of IKKα/ß in macrophages. Furthermore, GAS5 acted as a scaffold to strengthen the interaction between mTORC1 and ULK1, thus impaired ULK1/ATG13-mediated autophagy via increasing mTORC1 activity. Finally, restored autophagy by ATG13 overexpression suppressed the effect of GAS5 on M1 macrophage polarization. In conclusion, these results suggested that exosomal transfer of GAS5 promoted M1 macrophage polarization via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling in allergic rhinitis.

The intervention seasons of thoracic endovascular aortic repair impacted the outcomes for patients with type B aortic dissection.

Purpose: The objective of this research was to investigate whether seasonal variations influence the outcomes of type B aortic dissection (TBAD) patients with thoracic endovascular aortic repair (TEVAR). Patients and methods: From 2003 to 2020, a retrospective cohort study was performed, which included 1,123 TBAD patients who received TEVAR. Medical records were used to gather data on baseline characteristics. Outcomes including all-cause mortality and aortic-related adverse events (ARAEs) were tracked and analyzed. Results: Of the 1,123 TBAD patients in this study, 308 received TEVAR in spring (27.4%), 240 cases in summer (21.4%), 260 cases in autumn (23.2%), and 315 cases in winter (28.0%). Patients in the autumn group had a significantly lower risk of 1-year mortality than those in the spring group (hazard ratio: 2.66, 95% confidence interval: 1.06-6.67, p = 0.037). Kaplan-Meier curves revealed that patients who underwent TEVAR in autumn had a lower risk of 30-day ARAEs (p = 0.049) and 1-year mortality (p = 0.03) than those in spring. Conclusion: This study confirmed that TEVAR operated in autumn for TBAD was associated with a lower risk of 30-day ARAEs and 1-year mortality than in spring.

Nucleotide metabolism is linked to cysteine availability.

The small molecule erastin inhibits the cystine-glutamate antiporter, system xc-, which leads to intracellular cysteine and glutathione depletion. This can cause ferroptosis, which is an oxidative cell death process characterized by uncontrolled lipid peroxidation. Erastin and other ferroptosis inducers have been shown to affect metabolism but the metabolic effects of these drugs have not been systematically studied. To this end, we investigated how erastin impacts global metabolism in cultured cells and compared this metabolic profile to that caused by the ferroptosis inducer RAS-selective lethal 3 or in vivo cysteine deprivation. Common among the metabolic profiles were alterations in nucleotide and central carbon metabolism. Supplementing nucleosides to cysteine-deprived cells rescued cell proliferation in certain contexts, showing that these alterations to nucleotide metabolism can affect cellular fitness. While inhibition of the glutathione peroxidase GPX4 caused a similar metabolic profile as cysteine deprivation, nucleoside treatment did not rescue cell viability or proliferation under RAS-selective lethal 3 treatment, suggesting that these metabolic changes have varying importance in different scenarios of ferroptosis. Together, our study shows how global metabolism is affected during ferroptosis and points to nucleotide metabolism as an important target of cysteine deprivation.

A new potential risk factor for permanent cranial nerve injury following carotid body tumor resection.

Background: To quantify the association between the free distal segment length of the internal carotid artery (FDS-ICA) and permanent cranial nerve injury (p-CNI) following carotid body tumor (CBT) resection. Methods: This study is a case-control study. We surveyed 109 consecutive patients who underwent CBT resection between June 2015 and June 2020 at our single center. A total of 89 patients met the inclusion criteria and were selected for analysis. The FDS-ICA was measured by image post-processing software for computed tomography angiography (CTA). Postoperative p-CNI complications were evaluated using comprehensive statistical approaches. Results: The cohort was divided into 2 groups depending on the presence of p-CNI, namely the p-CNI group (n=17) and the non-CNI group (n=79). The average FDS-ICA of patients with p-CNI complications was shorter than that of those without p-CNI complications (P<0.001). For every 1 mm increase in FDS-ICA, there was an associated decrease of 8% in the risk of p-CNI (0.92, 95% CI: 0.85 to 0.98, P<0.05). Threshold effect analysis of the FDS-ICA on p-CNI identified that the FDS-ICA was 28.7 (95% CI: 23.8 to 30.9) mm. Conclusions: The results of this study revealed a significant independent association between FDS-ICA and permanent postoperative cranial nerve injury complications of CBTs. Further study is warranted to confirm these results in a larger patient cohort.

A novel photoelectrochemical array platform for ultrasensitive multiplex detection and subtype identification of HPV genes.

The rapid, low-cost and user-friendly methods for nucleic acid detection is urgently needed. Here we developed a miniaturized and convenient photoelectrochemical biosensor array (PEBA) platform for multiplexing and simultaneous detection of nucleic acid. The array system containing nine sensing units was integrated on one piece of conductive glass by laser etching and screen printing. Moreover, human papillomavirus (HPV), the main cause of cervical cancer, was selected as the model marker to evaluate the applicability of the fabricated PEBA. The proposed PEBA for HPV genotyping involved the TiO2@Au nanoparticles (NPs) as the photoelectrochemical (PEC) material and CdS quantum dots (CdS QDs)-labeled DNA hairpin probe anchored on the TiO2@Au NPs as the recognition element. With the addition of HPV target, the probe undergoes a significant conformational change and forces CdS QDs away from TiO2@Au, resulting in decreased PEC signals. The established array platform coupled with nucleic acid amplification exhibited high sensitivity as low as 0.1 copies/µL and a linear range of 0.6-600 copies/µL for nine HPV genotyping. Method evaluation with 40 clinical samples including 20 HPV-positive and 20 negative samples, gave a 97.5% concordance result in comparison with commercial kits. The genotyping results obtained by the PEBA reveal that HPV52, HPV18, and HPV11 are the most prevalent genotypes in positive samples, which is in good concordance with the official report concerning the trend of HPV prevalence among women with cervical lesions in Shenzhen. The designed PEBA platform has potential applications in extensive fields like biomedicine analysis and clinical healthcare diagnosis.

Peripheral Eosinophil Count Is Associated With the Prognosis of Patients With Type B Aortic Dissection Undergoing Endovascular Aortic Repair: A Retrospective Cohort Study.

Background Eosinophil count (EOS) has been proposed to provide prognostic information in multiple cardiovascular disorders. However, few researchers have investigated the predictive value of EOS for patients with type B aortic dissection who had thoracic endovascular repair. Methods and Results The authors reviewed the records of 912 patients with type B aortic dissection who were treated with thoracic endovascular repair in Changhai Hospital, Shanghai. By using receiver operating characteristic curve analysis, patients were divided into 2 groups based on the admission EOS cutoff value (<7.4×106/L [n=505] and ≥7.4×106/L [n=407]). To reduce selection bias, propensity score matching was applied. Multivariable regression analysis and Kaplan-Meier curves were performed to assess the association between EOS and long-term outcomes. Furthermore, we investigated nonlinear correlations between EOS and outcomes using general additive models with restricted cubic splines. In the matched population, lower EOS was associated with significantly higher 30-day mortality (4.1% vs 0%, P=0.007). There was no statistically difference in 30-day adverse events between the 2 groups (all P>0.05). Kaplan-Meier analysis revealed that patients with an EOS <7.4×106/L had a higher incidence of 1-year all-cause death (7.95% vs. 2.34%, P=0.008) and aortic-related death (5.98% vs 1.81%, P=0.023) than those with higher EOS. Multivariable Cox analysis showed that continuous EOS was independently associated with 1-year mortality (hazard ratio, 3.23 [95% CI, 1.20-8.33], P=0.019). In addition, we discovered a nonlinear association between EOS and 1-year outcomes. Conclusions Lower admission EOS values predict higher short- and long-term mortality after thoracic endovascular repair.

Fast Explainable Recommendation Model by Combining Fine-Grained Sentiment in Review Data.

With the rapid development of e-commerce, recommendation system has become one of the main tools that assists users in decision-making, enhances user's experience, and creates economic value. Since it is difficult to explain the implicit features generated by matrix factorization, explainable recommendation system has attracted more and more attention recently. In this paper, we propose an explainable fast recommendation model by combining fine-grained sentiment in review data (FSER, (Fast) Fine-grained Sentiment for Explainable Recommendation). We innovatively construct user-rating matrix, user-aspect sentiment matrix, and item aspect-descriptive word frequency matrix from the review-based data. And the three matrices are reconstructed by matrix factorization method. The reconstructed results of user-aspect sentiment matrix and item aspect-descriptive word frequency matrix can provide explanation for the final recommendation results. Experiments in the Yelp and Public Comment datasets demonstrate that, compared with several classical models, the proposed FSER model is in the optimal recommendation accuracy range and has lower sparseness and higher training efficiency than tensor models or neural network models; furthermore, it can generate explanatory texts and diagrams that have high interpretation quality.

Cytokines associated with immune response in atherosclerosis.

Inflammation is an essential mechanism of immune response that involves a large number of different immune cells. Atherosclerosis is essentially an inflammatory disease caused by inappropriate activities of immune cells. During this process, various cytokines activate immune cells, regulate and transmit immune cell signals, and stimulate a local inflammatory environment. In this study, we reviewed the cytokines associated with immune activity in atherosclerosis, including their roles in immune cell activation and mediating immune cell chemotaxis. The findings give important insights into inflammatory immune microenvironment, including basic mechanisms and interactions, providing new ideas and options for clinical detection and treatment of this disease.

Low red blood cell predicts high risk of temporary postoperative complications after carotid body tumor surgical resection.

Background: Carotid body tumor (CBT) is a rare paraganglioma located at the carotid bifurcation. The red blood cell count, hemoglobin, and hematocrit are indexes to be evaluated in blood routine tests. The purpose of this study was to clarify their predictive value for temporary postoperative complications in patients that had undergone CBT surgery. Methods: This retrospective trial included data from 169 patients received surgical treatment for CBT from October 2008 to September 2018 in this retrospective study. Postoperative follow-up was conducted under the guidance of both vascular surgeon and neurologist. The symptoms existed less than 2 years postoperatively were regarded as temporary injuries. The red blood cell count, hemoglobin, and hematocrit were obtained from the complete blood count results of the participants. Analyses of multilevel multivariable regression and descriptive statistics were conducted. Results: The baseline data showed no significant difference. Patients were predominantly women (53.8%), with a mean age of 42.6 years. The total incidence of temporary postoperative complications was 22 (13.0%), including transient ischemic attack (8, 4.7%), tongue bias (7, 4.1%), dysphagia (2, 1.2%), hoarseness (4, 1.8%), and eyelid ptosis (1, 2.4%). The univariate and multivariate regression analysis results revealed that the occurrence of temporary postoperative complications was increased with age [odd ratio (OR, 0.09; 95% CI (CI), 0.9-1.0; P = 0.014], length of operation time (OR, 1.0; 95% CI, 1.0-1.0; P = 0.005), Shamblin type II vs. I (OR, 0.1; 95% CI, 0.0-0.5; P = 0.008), red blood cell count postoperative (OR, 0.2; 95% CI, 0.1-0.8; P = 0.026), hemoglobin (OR, 0.9; 95% CI, 0.9-1.0; P = 0.011), and hematocrit (OR, 0.8; 95% CI, 0.7-1.0; P = 0.025). The smooth curve fitting showed that the trend of complications occurrence rate was reduced with the increase of patients' postoperative red blood cell count, hemoglobin, and hematocrit. Gender, weight, length of operation, Shamblin type, postoperative red blood cell count, hemoglobin, and hematocrit were included in the risk model with AUC = 0.86. Conclusion: These patients with CBT who received surgical resection with low postoperative red blood cell, hemoglobin, or hematocrit had a high risk of temporary postoperative complications. The risk prediction model established for predicting temporary postoperative complications showed satisfactory prediction effects.