Topologically Close-Packed Frank-Kasper C15 Phase Intermetallic Ir Alloy Electrocatalysts Enables High-Performance Proton Exchange Membrane Water Electrolyzer.

Chemical synthesis of unconventional topologically close-packed intermetallic nanocrystals (NCs) remains a considerable challenge due to the limitation of large volume asymmetry between the components. Here, a series of unconventional intermetallic Frank-Kasper C15 phase Ir2M (M = rare earth metals La, Ce, Gd, Tb, Tm) NCs is successfully prepared via a molten-salt assisted reduction method as efficient electrocatalysts for hydrogen evolution reaction (HER). Compared to the disordered counterpart (A1-Ir2Ce), C15-Ir2Ce features higher Ir-Ce coordination number that leads to an electron-rich environment for Ir sites. The C15-Ir2Ce catalyst exhibits excellent and pH-universal HER activity and requires only 9, 16, and 27 mV overpotentials to attain 10 mA cm-2 in acidic, alkaline, and neutral electrolytes, respectively, representing one of the best HER electrocatalysts ever reported. In a proton exchange membrane water electrolyzer, the C15-Ir2Ce cathode achieves an industrial-scale current density of 1 A cm-2 with a remarkably low cell voltage of 1.7 V at 80 °C and can operate stably for 1000 h with a sluggish voltage decay rate of 50 µV h-1. Theoretical investigations reveal that the electron-rich Ir sites intensify the polarization of *H2O intermediate on C15-Ir2Ce, thus lowering the energy barrier of the water dissociation and facilitating the HER kinetics.

Blood Urea Nitrogen to Left Ventricular Ejection Ratio as a Predictor of Short-Term Outcome in Acute Myocardial Infarction Complicated by Cardiogenic Shock.

INTRODUCTION: Cardiogenic shock (CS) is the most critical complication after acute myocardial infarction (AMI) with mortality above 50%. Both blood urea nitrogen and left ventricular ejection fraction were important prognostic indicators. We aimed to evaluate the prognostic value of admission blood urea nitrogen to left ventricular ejection fraction ratio (BUNLVEFr) in patients with AMI complicated by CS (AMI-CS). METHODS: 268 consecutive patients with AMI-CS were divided into two groups according to the admission BUNLVEFr cut-off value determined by Youden index. The primary endpoint was 30-day all-cause mortality and the secondary endpoint was the composite events of major adverse cardiovascular events (MACEs). Cox proportional hazard models were performed to analyze the association of BUNLVEFr with the outcome. RESULTS: The optimal cut-off value of BUNLVEFr is 16.63. The 30-day all-cause mortality and MACEs in patients with BUNLVEFr≥16.63 was significantly higher than in patients with BUNLVEFr<16.63 (30-day all-cause mortality: 66.2% vs. 17.1%, p < 0.001; 30-day MACEs: 80.0% vs. 48.0%, p < 0.001). After multivariable adjustment, BUNLVEFr≥16.63 remained an independent predictor for higher risk of 30-day all-cause mortality (HR = 3.553, 95% CI: 2.125-5.941, p < 0.001) and MACEs (HR = 2.026, 95% CI: 1.456-2.820, p < 0.001). Subgroup analyses found that the effect of BUNLVEFr was consistent in different subgroups (all p-interaction>0.05). CONCLUSION: The admission BUNLVEFr provided important prognostic information for AMI-CS patients.

Identification of potential therapeutic targets from bioinformatics analysis of necroptosis and immune infiltration in acute myocardial infarction.

INTRODUCTION: Acute myocardial infarction (AMI) is a serious, deadly disease with a high incidence. However, it remains unclear how necroptosis affects the pathophysiology of AMI. Using bioinformatic analyses, this study investigated necroptosis in AMI. METHODS: We obtained the GSE66360 dataset related to AMI by the GEO database. Venn diagrams were used to identify necroptosis-related differential genes (NRDEGs). The genes with differential expression in AMI were analyzed using gene set enrichment analysis, and a PPI network was established. A transcription factor prediction and enrichment analysis were conducted for the NRDEGs, and the relationships between AMI, NRDEGs, and immune cells were determined. Finally, in the additional dataset, NRDEG expression levels, immune infiltration, and ROC curve analysis were confirmed, and gene expression levels were further verified experimentally. RESULTS: GSEA revealed that necroptosis pathways were significantly enriched in AMI. We identified 10 NRDEGs, including TNF, TLR4, FTH1 and so on. Enrichment analysis indicated that the NOD-like receptor and NF-kappa B signaling pathways were significantly enriched. Four NRDEGs, FTH1, IFNGR1, STAT3, and TLR4, were identified; however, additional datasets and further experimental validation are required to confirm their roles. In addition, we determined that a high abundance of macrophages and neutrophils prompted AMI development. CONCLUSIONS: In this study, four potential genes that affect the development of AMI through necroptosis (FTH1, IFNGR1, STAT3, and TLR4) were identified. In addition, we found that a high abundance of macrophages and neutrophils affected AMI. This helps determine the pathological mechanism of necroptosis and immune cells that influence AMI and provides a novel strategy for targeted therapy.

LncRNA HAND2-AS1 Inhibited Colon Cancer Progression By Regulating miR-3118/ZG16 Axis.

LncRNA HAND2-AS1 is a novel cancer regulator, but the role and mechanisms of HAND2-AS1 involved with colon cancer (CC) progression remains unknown. The purpose of this research was to figure out how HAND2-AS1 regulates the progression of CC. Using qRT-PCR, we studied expression levels of miR-3118, HAND2-AS1, and ZG16 in CC tissues and cells. Protein levels of apoptosis-related proteins (Bax and Bcl-2) and ZG16 were quantified by western blotting. In vitro function analysis referred to western blotting, wound healing assay and CCK-8. The binding association among miR-3118, HAND2-AS1, and ZG16 was investigated using luciferase reporter and RIP assays. The functional role of HAND2-AS1 was analyzed using xenograft tumor models in vivo. In tissues and cells of CC, HAND2-AS1 was downregulated. We observed that HAND2-AS1 overexpression declined CC cell proliferation and migration while facilitating apoptosis. We further verified that when HAND2-AS1 is overexpressed it reduced CC tumor development in vivo. In CC cells and tissues, miR-3118 competed with HAND2-AS1 and was elevated. Further it was noted that the HAND2-AS1 when overexpressed, lessened the survival of CC cells, however overexpression of miR-3118 restored these changes. ZG16 was shown to be a target of miR-3118, it was found that ZG16 was downregulated in CC tissue and cells. We observed, high expression of ZG16 partially restored the enhanced malignant phenotype caused by miR-3118 overexpression. HAND2-AS1 inhibited CC progression by upregulating ZG16 expression through sponging miR-3118. Hence, HAND2-AS1/miR-3118/ZG16 axis could be a possible new target for CC treatment.

Analysis of predictive factors for late recurrence of atrial fibrillation after surgical ablation in patients undergoing rheumatic valve surgery.

OBJECTIVES: To identify independent predictors of late recurrence of atrial fibrillation (AF) after surgical ablation in patients undergoing rheumatic valve surgery. METHODS: A total of 258 patients who underwent surgical ablation for AF with rheumatic heart disease at our hospital between January 2019 and June 2022 were retrospectively included. The patients were followed up for 12 months. Late recurrence was defined as any AF recurrence longer than 30 s between 3 and 12 months. Patients with or without late recurrence were divided into non-recurrence and recurrence groups. Univariate and multivariate analyses were performed to identify the predictors of late recurrence. RESULTS: The in-hospital mortality rate was 0.8% (2/258), and the late recurrence rate of AF was 38.4%, including 152 and 95 cases in the non-recurrent and recurrent groups respectively, with a follow-up completion rate of 96.5% (247/256). There were no deaths during follow-up, two patients (0.8%) experienced a stroke, and one patient (0.4%) experienced gastrointestinal hemorrhage. The results of the univariate and multivariate analyses of the preoperative risk factors for late recurrence showed a left atrial (LA) anteroposterior diameter ≥ 52.9 mm (odds ratio [OR] = 2.366, 95% confidence interval [CI] = 1.089-5.138, P = 0.030], ratio of the superoinferior to the anteroposterior diameters of LA (S-AR) < 1.19 (OR = 4.639, 95% CI = 2.181-9.865, P < 0.001), and AF duration ≥ 39 months (OR = 6.152, 95% CI = 2.897-13.061, P < 0.001), and cardiothoracic ratio ≥ 0.63 (OR = 2.716, 95% CI = 1.314-5.612, P = 0.007) were the most significant independent risk factors. CONCLUSIONS: LA anteroposterior diameter ≥ 52.9 mm, S-AR < 1.19, and AF duration ≥ 36 months and cardiothoracic ratio ≥ 0.63 are independent predictors for late recurrence of AF after surgical ablation in patients undergoing rheumatic valve surgery.

Development of a machine learning-based model to predict major adverse events after surgery for type A aortic dissection complicated by malnutrition.

Objective: This study aims to develop a predictive model for the risk of major adverse events (MAEs) in type A aortic dissection (AAAD) patients with malnutrition after surgery, utilizing machine learning (ML) algorithms. Methods: We retrospectively collected clinical data from AAAD patients with malnutrition who underwent surgical treatment at our center. Through least absolute shrinkage and selection operator (LASSO) regression analysis, we screened for preoperative and intraoperative characteristic variables. Based on the random forest (RF) algorithm, we constructed a ML predictive model, and further evaluated and interpreted this model. Results: Through LASSO regression analysis and univariate analysis, we ultimately selected seven feature variables for modeling. After comparing six different ML models, we confirmed that the RF model demonstrated the best predictive performance in this dataset. Subsequently, we constructed a model using the RF algorithm to predict the risk of postoperative MAEs in AAAD patients with malnutrition. The test set results indicated that this model has excellent predictive efficacy and clinical applicability. Finally, we employed the Shapley additive explanations (SHAP) method to further interpret the predictions of this model. Conclusion: We have successfully constructed a risk prediction model for postoperative MAEs in AAAD patients with malnutrition using the RF algorithm, and we have interpreted the model through the SHAP method. This model aids clinicians in early identification of high-risk patients for MAEs, thereby potentially mitigating adverse clinical outcomes associated with malnutrition.

Modulating the Bader Charge Transfer in Single p-Block Atoms Doped Pd Metallene for Enhanced Oxygen Reduction Electrocatalysis.

Metallene is considered as an emerging family of electrocatalysts due to its atomically layered structure and unique surface stress. Here we propose a strategy to modulate the Bader charge transfer (BCT) between Pd surface and oxygenated intermediates via p-d electronic interaction by introducing single-atom p-block metal (M=In, Sn, Pb, Bi) into Pd metallene nanosheets towards efficient oxygen reduction reaction (ORR). X-ray absorption and photoelectron spectroscopy suggests that doping p-block metals could facilitate electron transfer to Pd sites and thus downshift the d-band center of Pd and weaken the adsorption energy of O intermediates. Among them, the developed Bi-Pd metallene shows extraordinarily high ORR mass activity of 11.34 A mgPd -1 and 0.86 A mgPd -1 at 0.9 V and 0.95 V in alkaline solution, respectively, representing the best Pd-based ORR electrocatalysts ever reported. In the cathode of a Zinc-air battery, Bi-Pd metallene could achieve an open-circuit voltage of 1.546 V and keep stable for 760 h at 10 mA cm-2. Theoretical calculations suggest that the BCT between Pd surface and *OO intermediates greatly affects the bond length between them (dPd-*OO) and Bi doping could appropriately reduce the amount of BCT and stretch the dPd-*OO, thus enhancing the ORR activity.

Risk prediction and prognostic analysis of post-implantation syndrome after thoracic endovascular aortic repair.

This study aimed to establish a predictive model for the risk of post-thoracic endovascular aortic repair (TEVAR) post-implantation syndrome (PIS) in type B aortic dissection (TBAD) patients, assisting clinical physicians in early risk stratification and decision management for high-risk PIS patients. This study retrospectively analyzed the clinical data of 547 consecutive TBAD patients who underwent TEVAR treatment at our hospital. Feature variables were selected through LASSO regression and logistic regression analysis to construct a nomogram predictive model, and the model's performance was evaluated. The optimal cutoff value for the PIS risk nomogram score was calculated through receiver operating characteristic (ROC) curve analysis, further dividing patients into high-risk group (HRG) and low-risk group (LRG), and comparing the short to midterm postoperative outcomes between the two groups. In the end, a total of 158 cases (28.9%) experienced PIS. Through LASSO regression analysis and multivariable logistic regression analysis, variables including age, emergency surgery, operative time, contrast medium volume, and number of main prosthesis stents were selected to construct the nomogram predictive model. The model achieved an area under the curve (AUC) of 0.86 in the training set and 0.82 in the test set. Results from calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) demonstrated that the predictive model exhibited good performance and clinical utility. Furthermore, after comparing the postoperative outcomes of HRG and LRG patients, we found that the incidence of postoperative PIS significantly increased in HRG patients. The duration of ICU stay and mechanical assistance time was prolonged, and the incidence of postoperative type II entry flow and acute kidney injury (AKI) was higher. The risk of aortic-related adverse events (ARAEs) and major adverse events (MAEs) at the first and twelfth months of follow-up also significantly increased. However, there was no significant difference in the mortality rate during hospitalization. This study established a nomogram model for predicting the risk of PIS in patients with TBAD undergoing TEVAR. It serves as a practical tool to assist clinicians in early risk stratification and decision-making management for patients.

Clinical usefulness of psoas muscle thickness for the prognosis of acute type A aortic dissection patients undergoing total arch replacement.

Background: Sarcopenia has emerged as a comprehensive predictor of mortality in diseased populations. The aim of this study was to evaluate the prognostic and predictive value of psoas muscle thickness/height (PMTH) measurement in patients with acute type A aortic dissection (AAAD). Methods: A retrospective analysis of patients (from January 2020 to December 2020) who underwent AAAD surgery at our institution was conducted. PMTH, as a measure of sarcopenia, was measured by preoperative computed tomography. Patients were classified into two groups according to the cut-off value of PMTH. To balance potential bias, a 1:1 propensity score matching (PSM) with a caliper 0.05 was conducted. Results: PSM analysis created 68 pairs of patients. In short-term outcomes, a lower PMTH value was strongly correlated with higher in-hospital mortality and renal failure. Receiver operating characteristic (ROC) analysis suggested that sarcopenia had good predictive capabilities in in-hospital mortality, with the area under curve (AUC) of 0.81 [95% confidence interval (CI): 0.64-0.97]. During a median follow-up of 37 months, 24 (19.4%) patients died, including 16 in low PMTH group and 8 in high PMTH group. Kaplan-Meier analysis indicated the sarcopenia significantly affected long-term survival [log-rank P=0.02; hazard ratio (HR) 2.53 (95% CI: 1.13-5.66)]. Multivariable Cox regression analysis revealed that sarcopenia was an independent predictor for decreased survival [HR 2.73 (95% CI: 1.15-8.78)]. Conclusions: Sarcopenia defined from the PMTH may be a useful tool for predicting short- and long-term mortality in patients after AAAD surgery.

miR-485-3p targets SIRT1 in vascular smooth muscle cells mediating the occurrence of aortic dissection.

Studies have demonstrated a close correlation between MicroRNA and the occurrence of aortic dissection (AD). However, the molecular mechanisms underlying this relationship have not been fully elucidated and further exploration is still required. In this study, we found that miR-485-3p was significantly upregulated in human aortic dissection tissues. Meanwhile, we constructed in vitro AD models in HAVSMCs, HAECs and HAFs and found that the expression of miR-485-3p was increased only in HAVSMCs. Overexpression or knockdown of miR-485-3p in HAVSMCs could regulate the expression of inflammatory cytokines IL1ß, IL6, TNF-α, and NLRP3, as well as the expression of apoptosis-related proteins BAX/BCL2 and Cleaved caspase3/Caspase3. In the in vivo AD model, we have observed that miR-485-3p regulates vascular inflammation and apoptosis, thereby participating in the modulation of AD development in mice. Based on target gene prediction, we have validated that SIRT1 is a downstream target gene of miR-485-3p. Furthermore, by administering SIRT1 agonists and inhibitors to mice, we observed that the activation of SIRT1 alleviates vascular inflammation and apoptosis, subsequently reducing the incidence of AD. Additionally, functional reversal experiments revealed that overexpression of SIRT1 in HAVSMCs could reverse the cell inflammation and apoptosis mediated by miR-485-3p. Therefore, our research suggests that miR-485-3p can aggravate inflammation and apoptosis in vascular smooth muscle cells by suppressing the expression of SIRT1, thereby promoting the progression of aortic dissection.

Surgical management of the aortic root in acute type A aortic dissection: A comparative analysis.

BACKGROUND: This study aimed to assess the early- and mid-term outcomes of aortic root repair and replacement, and to provide evidence to improve root management in acute type A aortic dissection (AAAD). METHODS: This study enrolled 455 patients who underwent AAAD root repair (n = 307) or replacement (n = 148) between January 2016 and December 2017. Inverse probability of treatment weighting (IPTW) method was used to control for treatment selection bias. The primary outcomes were in-hospital mortality, mid-term survival, and proximal aortic reintervention. RESULTS: The success rate of root repair was 99.7%. The in-hospital mortality in the conservative root repair (CRR) and aggressive root replacement (ARR) were 8.1% and 10.8%. The median follow-up time was 67.76 months (IQR, 67-72 months). After adjusting for baseline factors, there was no significant differences in mid-term survival (p = .750) or the proximal aortic reintervention rate (p = .550) between the two groups. According to Cox analysis, age, hypertension, severe aortic regurgitation, CPB time, and concomitant CABG were all factors associated with mid-term mortality. Regarding reintervention, multivariate analysis identified renal insufficiency, bicuspid aortic valve, root diameter ≥ 45 mm, and severe aortic regurgitation as risk factors, while CRR did not increase the risk of reintervention. The subgroup analysis revealed heterogeneity in the effects of surgical treatment across diverse populations based on a variety of risk factors. CONCLUSIONS: For patients with AAAD, both CRR and ARR are appropriate operations with promising early and mid-term outcomes. The effects of treatment show heterogeneity across diverse populations based on various risk factors.

The prognostic value of preoperative systemic inflammatory response index in predicting outcomes of acute type A aortic dissection patients underwent surgical treatment.

Background: The systemic inflammatory response index (SIRI) is a novel inflammatory-immune biological marker that has prognostic value in various cardiovascular diseases. This study aims to investigate the relationship between SIRI and short-term and long-term prognosis in patients with acute type A aortic dissection (AAAD) underwent surgical treatment. Methods: We conducted a retrospective analysis of patients with AAAD who underwent emergency surgical treatment at our center. Through multifactorial logistics regression analysis and cox proportional hazards regression analysis, we identified SIRI as an independent risk factor for major adverse events (MAEs) and long-term aorta-related adverse events (ARAEs) post-surgery. The optimal cutoff value of preoperative SIRI was determined using receiver operating characteristic (ROC) curve analysis, and patients were divided into low SIRI group and high SIRI group. The prognostic outcomes at different time points post-surgery for the two groups of patients were analyzed using Kaplan-Meier survival analysis, and the significance was determined by log-rank test. Results: A total of 691 AAAD patients were included in this study. Among them, 50 patients (7.2%) died within 30 days post-surgery, and 175 patients (25.3%) experienced MAEs. A total of 641 patients were followed up, with an average follow-up time of 33.5 ± 17.5 months, during which 113 patients (17.6%) experienced ARAEs. The results of multifactorial logistics regression analysis and cox proportional hazards regression analysis showed that SIRI was an independent risk factor for postoperative MAEs (OR=3.148, 95%CI[1.650-6.006], p<0.001) and ARAEs (HR=2.248, 95%CI[1.050-4.809], p<0.037). Kaplan-Meier analysis demonstrated that the MAEs-free survival in the high SIRI group was significantly lower than that in the low SIRI group, and a similar trend was observed in the ARAEs-free survival during follow-up (log-rank test, p<0.001). Conclusion: Preoperative SIRI is significantly associated with the short-term and long-term prognosis of AAAD patients underwent emergency open surgery, demonstrating its valuable prognostic value. Therefore, preoperative SIRI is a reliable biological marker that can serve as a valuable tool for preoperative risk stratification and decision management.

Clinical predictive value of the age, creatinine, and ejection fraction score in patients in acute type A aortic dissection after total arch replacement.

The age, creatinine, and ejection fraction (ACEF) score has been accepted as a predictor of poor outcome in elective operations. This study aimed to investigate the predictive value of ACEF score in acute type A aortic dissection (AAAD) patients after total arch replacement. A total of 227 AAAD patients from July 2021 and June 2022 were enrolled and divided into Tertiles 1 (ACEF ≤ 0.73), Tertiles 2 (0.73 < ACEF ≤ 0.95), and Tertiles 3 (ACEF > 0.95). Using inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Cox logistic regression was used to further evaluate the survival prediction ability of ACEF score. The in-hospital mortality was 9.8%. After IPTW, in the baseline characteristics reached an equilibrium, a higher ACEF score before operation still associated with higher in-hospital mortality. After 1 year follow-up, 184 patients (90.6%) survival. Multivariable analysis revealed that ACEF score (adjusted hazard ratio 1.68; 95% confidence interval 1.34-4.91; p = 0.036) and binary ACEF score (adjusted HR 2.26; 95% CI 1.82-6.20; p < 0.001) was independently associated with 1-year survival. In addition, net reclassification improvement (NRI) and integrated differentiation improvement (IDI) verified that the ACEF score and binary ACEF score is an accurate predictive tool in clinical settings. In conclusions, ACEF score could be considered as a useful tool to risk stratification in patients with AAAD before operation in daily clinical work.

Preoperative blood urea nitrogen-to-serum albumin ratio for prediction of in-hospital mortality in patients who underwent emergency surgery for acute type A aortic dissection.

The study aimed to assess the predictive value of blood urea nitrogen (BUN)-to-albumin ratio (BA-R) for in-hospital mortality in patients undergoing emergency surgery for acute type A aortic dissection (ATAAD). Patients who were diagnosed with ATAAD and underwent emergency surgery within 48 hours of onset at our hospital between January 2015 and December 2021 were included in this study. The primary endpoint of this study was postoperative in-hospital mortality (POIM). The data of the survivors and non-survivors were retrospectively compared analyses. A total of 557 ATAAD patients were included, with 505 survivors and 52 non-survivors. The preoperative BA-R of the non-survivor group was significantly higher than that of the survivor group (P < 0.001). Univariate regression analysis showed that preoperative BA-R, serum creatinine level, SA level, D-dimer level, age, myocardial ischemia, cerebral ischemia, and aortic clamp time were risk factors for POIM. In addition, multivariable regression analysis showed that preoperative BA-R ≥ 0.155 mmol/g was a risk factor for POIM (odds ratio, 6.815 [3.582-12.964]; P < 0.001). Receiver operating characteristic curve indicated that the cut-off point for preoperative BA-R was ≥0.155 mmol/g (area under the curve =0.874). The sensitivity and specificity of preoperative BA-R in predicting the POIM of patients who underwent emergency surgery for ATAAD were 84.6% and 71.3%, respectively (95% confidence interval, 0.829-0.919; P < 0.001). In conclusion, Preoperative BA-R is a simple, rapid, and potentially useful prognostic indicator of POIM in patients with ATAAD. BAR: Blood urea nitrogen-to-albumin ratio, BUN: Blood urea nitrogen, SA: Serum albumin, REF: Reference. The aim of this study was to evaluate the prognostic value of BA-R for the prediction of postoperative in-hospital mortality in patients who underwent emergency surgery for ATAAD. A total of 557 patients with ATAAD were enrolled, and 505 survived while 52 did not. The preoperative BA-R of the non-survivor group was significantly higher than that of the survivor group (0.27 [0.18, 0.46] vs. 0.12 [0.10, 0.16]mmol/g; P < 0.001). The study showed that preoperative BA-R ≥ 0.155 mmol/g was a risk factor for POIM (odds ratio, 6.815 [3.582-12.964]; P < 0.001). ROC curve indicated that the cut-off point for preoperative BA-R was ≥0.155 mmol/g (AUC = 0.874) and the sensitivity and specificity were 84.6% and 71.3%, respectively (95% CI, 0.829-0.919; P < 0.001). We believe that our study makes a significant contribution to the literature because we found preoperative BA-R to be a simple, rapid, and potentially useful prognostic indicator of postoperative in-hospital mortality in patients with ATAAD.

Synthetic biology for Taxol biosynthesis and sustainable production.

Incomplete understanding of the biosynthetic pathway of the anticancer compound Taxol hinders its production by metabolic engineering. Recent reports by Jiang et al. and other groups now describe the missing steps in Taxol biosynthesis, notably including oxetane ring formation. These findings will promote the sustainable production of Taxol through synthetic biology.

Rules of engagement for condensins and cohesins guide mitotic chromosome formation.

During mitosis, interphase chromatin is rapidly converted into rod-shaped mitotic chromosomes. Using Hi-C, imaging, proteomics and polymer modeling, we determine how the activity and interplay between loop-extruding SMC motors accomplishes this dramatic transition. Our work reveals rules of engagement for SMC complexes that are critical for allowing cells to refold interphase chromatin into mitotic chromosomes. We find that condensin disassembles interphase chromatin loop organization by evicting or displacing extrusive cohesin. In contrast, condensin bypasses cohesive cohesins, thereby maintaining sister chromatid cohesion while separating the sisters. Studies of mitotic chromosomes formed by cohesin, condensin II and condensin I alone or in combination allow us to develop new models of mitotic chromosome conformation. In these models, loops are consecutive and not overlapping, implying that condensins do not freely pass one another but stall upon encountering each other. The dynamics of Hi-C interactions and chromosome morphology reveal that during prophase loops are extruded in vivo at ~1-3 kb/sec by condensins as they form a disordered discontinuous helical scaffold within individual chromatids.

Chest pain in a patient with transthyretin cardiac amyloidosis: A case report.

Key Clinical Message: Patients with transthyretin cardiac amyloidosis (ATTR-CM) commonly present with dyspnea, fatigue, and edema. In our case, the main presentation was exertional angina, which was atypical in patients with ATTR-CM and should be paid more attention to. Abstract: A 54-year-old woman was admitted with a complaint of exertional chest pain, and she had a history of hypertension. The results of the electrocardiogram and echocardiography revealed the clues of cardiac amyloidosis, and the patient was finally diagnosed with transthyretin cardiac amyloidosis, then she received tafamidis, and the symptoms improved significantly.

Detection of common pathogenesis of rheumatoid arthritis and atherosclerosis via microarray data analysis.

Despite extensive research reveal rheumatoid arthritis (RA) is related to atherosclerosis (AS), common pathogenesis between these two diseases still needs to be explored. In current study, we explored the common pathogenesis between rheumatoid arthritis (RA) and atherosclerosis (AS) by identifying 297 Differentially Expressed Genes (DEGs) associated with both diseases. Through KEGG and GO functional analysis, we highlighted the correlation of these DEGs with crucial biological processes such as the vesicle transport, immune system process, signaling receptor binding, chemokine signaling and many others. Employing Protein-Protein Interaction (PPI) network analysis, we elucidated the associations between DEGs, revealing three gene modules enriched in immune system process, vesicle, signaling receptor binding, Pertussis, and among others. Additionally, through CytoHubba analysis, we pinpointed 11 hub genes integral to intergrin-mediated signaling pathway, plasma membrane, phosphotyrosine binding, chemokine signaling pathway and so on. Further investigation via the TRRUST database identified two key Transcription Factors (TFs), SPI1 and RELA, closely linked with these hub genes, shedding light on their regulatory roles. Finally, leveraging the collective insights from hub genes and TFs, we proposed 10 potential drug candidates targeting the molecular mechanisms underlying RA and AS pathogenesis. Further investigation on xCell revealed that 14 types of cells were all different in both AS and RA. This study underscores the shared pathogenic mechanisms, pivotal genes, and potential therapeutic interventions bridging RA and AS, offering valuable insights for future research and clinical management strategies.

Ogataea polymorpha as a next-generation chassis for industrial biotechnology.

Ogataea (Hansenula) polymorpha is a nonconventional yeast with some unique characteristics, including fast growth, thermostability, and broad substrate spectrum. Other than common applications for protein production, O. polymorpha is attracting interest for chemical and protein production from methanol; a promising feedstock for the next-generation biomanufacturing due to its abundant sources and excellent characteristics. Benefiting from the development of synthetic biology, it has been engineered to produce value-added chemicals by extensively rewiring cellular metabolism. This Review discusses recently developed synthetic biology tools of O. polymorpha. The advances of chemicals production and systems biology were reviewed comprehensively. Finally, we look ahead to the developments of biomanufacturing in O. polymorpha to make an overall understanding of this chassis for academia and industry.

Quality of life in young patients with acute type a aortic dissection in China: comparison with Marfan syndrome and non-Marfan syndrome.

BACKGROUND: There is a paucity of Chinese studies evaluating the quality of life (QoL) in young acute type A aortic dissection (AAAD) patients with Marfan syndrome. METHODS: Young adult AAAD patients (younger than 45 years old) underwent surgical treatment at our institution from January 2017 to December 2020 were consecutive enrolled. The hospital survivors completed 1 year of follow up. Patients were divided into two groups according to the presence or absence of Marfan syndrome (MFS). A 1:1 propensity score matching (PSM) with a caliper 0.2 was conducted to balance potential bias in baseline. The follow-up data were analyzed primarily for change in quality of life and anxiety status. RESULTS: After PSM, 32 comparable pairs were matched. The baseline data were comparable and postoperative complications were similar between groups. In terms of SF-36 scale, the role physical, bodily pain, role emotional and mental health subscales were no significantly improved in MFS patients over time. At 1 year after discharged, the subscale of mental health and bodily pain were significantly lower in the MFS group than in the non-MFS group. In terms of HADS assessments, the level of anxiety in MFS patients was significantly higher than in non-MFS patients at 1 year after discharged. CONCLUSIONS: The QoL in young AAAD patients with MFS is lower than those without MFS after surgery. This may be associated with the uncontrollable persistent chronic pain and the uncertainty and concerns for the disease's progression.