Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency.

Of all known cultured stem cell types, pluripotent stem cells (PSCs) sit atop the landscape of developmental potency and are characterized by their ability to generate all cell types of an adult organism. However, PSCs show limited contribution to the extraembryonic placental tissues in vivo. Here, we show that a chemical cocktail enables the derivation of stem cells with unique functional and molecular features from mice and humans, designated as extended pluripotent stem (EPS) cells, which are capable of chimerizing both embryonic and extraembryonic tissues. Notably, a single mouse EPS cell shows widespread chimeric contribution to both embryonic and extraembryonic lineages in vivo and permits generating single-EPS-cell-derived mice by tetraploid complementation. Furthermore, human EPS cells exhibit interspecies chimeric competency in mouse conceptuses. Our findings constitute a first step toward capturing pluripotent stem cells with extraembryonic developmental potentials in culture and open new avenues for basic and translational research. VIDEO ABSTRACT.

A XEN-like State Bridges Somatic Cells to Pluripotency during Chemical Reprogramming.

Somatic cells can be reprogrammed into pluripotent stem cells (PSCs) by using pure chemicals, providing a different paradigm to study somatic reprogramming. However, the cell fate dynamics and molecular events that occur during the chemical reprogramming process remain unclear. We now show that the chemical reprogramming process requires the early formation of extra-embryonic endoderm (XEN)-like cells and a late transition from XEN-like cells to chemically-induced (Ci)PSCs, a unique route that fundamentally differs from the pathway of transcription factor-induced reprogramming. Moreover, precise manipulation of the cell fate transition in a step-wise manner through the XEN-like state allows us to identify small-molecule boosters and establish a robust chemical reprogramming system with a yield up to 1,000-fold greater than that of the previously reported protocol. These findings demonstrate that chemical reprogramming is a promising approach to manipulate cell fates.

Chemical reprogramming of human somatic cells to pluripotent stem cells.

Cellular reprogramming can manipulate the identity of cells to generate the desired cell types1-3. The use of cell intrinsic components, including oocyte cytoplasm and transcription factors, can enforce somatic cell reprogramming to pluripotent stem cells4-7. By contrast, chemical stimulation by exposure to small molecules offers an alternative approach that can manipulate cell fate in a simple and highly controllable manner8-10. However, human somatic cells are refractory to chemical stimulation owing to their stable epigenome2,11,12 and reduced plasticity13,14; it is therefore challenging to induce human pluripotent stem cells by chemical reprogramming. Here we demonstrate, by creating an intermediate plastic state, the chemical reprogramming of human somatic cells to human chemically induced pluripotent stem cells that exhibit key features of embryonic stem cells. The whole chemical reprogramming trajectory analysis delineated the induction of the intermediate plastic state at the early stage, during which chemical-induced dedifferentiation occurred, and this process was similar to the dedifferentiation process that occurs in axolotl limb regeneration. Moreover, we identified the JNK pathway as a major barrier to chemical reprogramming, the inhibition of which was indispensable for inducing cell plasticity and a regeneration-like program by suppressing pro-inflammatory pathways. Our chemical approach provides a platform for the generation and application of human pluripotent stem cells in biomedicine. This study lays foundations for developing regenerative therapeutic strategies that use well-defined chemicals to change cell fates in humans.

Integrating Reinforcement Learning and Monte Carlo Tree Search for enhanced neoantigen vaccine design.

Recent advances in cancer immunotherapy have highlighted the potential of neoantigen-based vaccines. However, the design of such vaccines is hindered by the possibility of weak binding affinity between the peptides and the patient's specific human leukocyte antigen (HLA) alleles, which may not elicit a robust adaptive immune response. Triggering cross-immunity by utilizing peptide mutations that have enhanced binding affinity to target HLA molecules, while preserving their homology with the original one, can be a promising avenue for neoantigen vaccine design. In this study, we introduced UltraMutate, a novel algorithm that combines Reinforcement Learning and Monte Carlo Tree Search, which identifies peptide mutations that not only exhibit enhanced binding affinities to target HLA molecules but also retains a high degree of homology with the original neoantigen. UltraMutate outperformed existing state-of-the-art methods in identifying affinity-enhancing mutations in an independent test set consisting of 3660 peptide-HLA pairs. UltraMutate further showed its applicability in the design of peptide vaccines for Human Papillomavirus and Human Cytomegalovirus, demonstrating its potential as a promising tool in the advancement of personalized immunotherapy.

Association between the stress hyperglycemia ratio and 28-day all-cause mortality in critically ill patients with sepsis: a retrospective cohort study and predictive model establishment based on machine learning.

BACKGROUND: Sepsis is a severe form of systemic inflammatory response syndrome that is caused by infection. Sepsis is characterized by a marked state of stress, which manifests as nonspecific physiological and metabolic changes in response to the disease. Previous studies have indicated that the stress hyperglycemia ratio (SHR) can serve as a reliable predictor of adverse outcomes in various cardiovascular and cerebrovascular diseases. However, there is limited research on the relationship between the SHR and adverse outcomes in patients with infectious diseases, particularly in critically ill patients with sepsis. Therefore, this study aimed to explore the association between the SHR and adverse outcomes in critically ill patients with sepsis. METHODS: Clinical data from 2312 critically ill patients with sepsis were extracted from the MIMIC-IV (2.2) database. Based on the quartiles of the SHR, the study population was divided into four groups. The primary outcome was 28-day all-cause mortality, and the secondary outcome was in-hospital mortality. The relationship between the SHR and adverse outcomes was explored using restricted cubic splines, Cox proportional hazard regression, and Kaplan‒Meier curves. The predictive ability of the SHR was assessed using the Boruta algorithm, and a prediction model was established using machine learning algorithms. RESULTS: Data from 2312 patients who were diagnosed with sepsis were analyzed. Restricted cubic splines demonstrated a "U-shaped" association between the SHR and survival rate, indicating that an increase in the SHR is related to an increased risk of adverse events. A higher SHR was significantly associated with an increased risk of 28-day mortality and in-hospital mortality in patients with sepsis (HR > 1, P < 0.05) compared to a lower SHR. Boruta feature selection showed that SHR had a higher Z score, and the model built using the rsf algorithm showed the best performance (AUC = 0.8322). CONCLUSION: The SHR exhibited a U-shaped relationship with 28-day all-cause mortality and in-hospital mortality in critically ill patients with sepsis. A high SHR is significantly correlated with an increased risk of adverse events, thus indicating that is a potential predictor of adverse outcomes in patients with sepsis.

Access to cyclohexadiene and benzofuran derivatives via catalytic arene cyclopropanation of α-cyanodiazocarbonyl compounds.

The arene cyclopropanation between diazo compounds and benzene is well known to produce a tautomeric mixture of norcaradiene and cycloheptatriene in favour of the latter species. Nevertheless, previous studies have suggested that the initially formed norcaradiene can be stabilized by a C-7 cyano group with prevention of its 6π-electrocyclic ring opening. According to this feature, a synthetic route to functionalized cyclohexadienes has been designed using α-cyanodiazoacetates and α-diazo-ß-ketonitriles as the starting materials, respectively. The Rh2(esp)2-catalyzed arene cyclopropanation of α-cyanodiazoacetates in benzene afforded the expected 7-alkoxycarbonyl-7-cyanonorcaradienes as isolable compounds, which then served as templates for the second cyclopropanation with ethyl diazoacetate or α-cyanodiazocarbonyls to enable the formation of bis(cyclopropanated) adducts. Their subsequent treatment with SmI2 triggered a double ring-opening process, allowing for the generation of 1,4- and/or 1,3-cyclohexadienes as either regio- or diastereomeric mixtures. On the other hand, the norcaradienes generated from phenyl- or methyl-substituted α-diazo-ß-ketonitriles were found to undergo an in situ rearrangement to yield dihydrobenzofurans that could be converted to benzofuran derivatives by DDQ oxidation.

Relationship between the magnitude of haemoglobin changes and long-term mortality in patients with sepsis: a retrospective cohort study.

BACKGROUND: Sepsis is a common and severe disease with a high mortality rate in intensive care unit (ICU). The hemoglobin (HGB) level is a key parameter for oxygen supply in sepsis. Although HGB is associated with the progression of inflammation in sepsis patients, its role as a marker following sepsis treatment remains unclear. Here, we studied the correlation between early temporal changes in HGB levels and long-term mortality rates in septic patients. METHOD: In this retrospective study of data on patients with sepsis from the Medical Information Mart for Intensive Care (MIMIC) IV database, the outcome was long-term mortality. Patients were divided based on the cut-off of the HGB percentage for receiver operating characteristic (ROC) curve calculation. Kaplan-Meier (KM) survival curves and Cox proportional hazards regression models were used to analyse the associations between groups and outcomes. Propensity score matching (PSM) was used to verify the results. RESULTS: In this study, 2042 patients with sepsis and changes in HGB levels at day 4 after admission compared to day 1 were enrolled and divided into two groups: group 1 (n = 1147) for those with reduction of HGB < 7% and group 2 (n = 895) for those with dropping ≥ 7%. The long-term survival chances of sepsis with less than a 7% reduction in the proportion of HGB at day four were significantly higher than those of patients in the group with a reduction of 7% or more. After adjusting for covariates in the Cox model, the hazard ratios (HRs) with 95% confidence intervals (CIs) for long-term all-cause mortality in the group with a reduction of 7% or more were as follows: 180 days [HR = 1.41, 95% CI (1.22 to 1.63), P < 0.001]; 360 days [HR = 1.37, 95% CI (1.21 to 1.56), P < 0.001]; 540 days [HR = 1.35, 95% CI (1.20 to 1.53), P < 0.001]; 720 days [HR = 1.45, 95% CI (1.29 to 1.64), P < 0.001]. Additionally, the long-term survival rates, using Kaplan-Meier analysis, for the group with a reduction of 7% or more were lower compared to the group with less than 7% reduction at 180 days (54.3% vs. 65.3%, P < 0.001), 360 days (42.3% vs. 50.9%, P < 0.001), 540 days (40.2% vs. 48.6%, P < 0.001), and 720 days (35.5% vs. 46.1%, P < 0.001). The same trend was obtained after using PSM. CONCLUSION: A ≥ 7% decrease in HGB levels on Day 4 after admission was associated with worse long-term prognosis in sepsis patients admitted to the ICU.

Negative emotions increase unhealthy eating: Evidence from the Wuhan lockdown during COVID-19.

This paper studies how negative emotions like stress, anxiety, and boredom can affect unhealthy food consumption. Using the Wuhan lockdown as an external shock, we examine the changes in food consumption in a city that was not in lockdown. We applied the difference-in-differences method to a large scanner dataset from a retail monopoly in China. Our findings reveal that negative emotions induced by the pandemic lockdown significantly elevated consumer spending on unhealthy food items such as crisps, sugary beverages, regular soda, and low-alcohol beverages. Notably, the effect of unhealthy food consumption was more pronounced among younger and wealthier demographics. Triggering factors, like information about confirmed new deaths and infections as well as proximity to local hospitals, were found to strongly influence the consumption of unhealthy foods. Overall, the lockdown's impact extended beyond short-term increases in snack consumption to substantial increases in overall dietary and nutritional intake.

Development and validation of a nomogram for predicting in-hospital mortality in ICU patients with infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is a disease with high in-hospital mortality. The objective of the present investigation was to develop and validate a nomogram that precisely anticipates in-hospital mortality in ICU individuals diagnosed with infective endocarditis. METHODS: Retrospectively collected clinical data of patients with IE admitted to the ICU in the MIMIC IV database were analyzed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify potential hazards. A logistic regression model incorporating multiple factors was established, and a dynamic nomogram was generated to facilitate predictions. To assess the classification performance of the model, an ROC curve was generated, and the AUC value was computed as an indicator of its diagnostic accuracy. The model was subjected to calibration curve analysis and the Hosmer-Lemeshow (HL) test to assess its goodness of fit. To evaluate the clinical relevance of the model, decision-curve analysis (DCA) was conducted. RESULTS: The research involved a total of 676 patients, who were divided into two cohorts: a training cohort comprising 473 patients and a validation cohort comprising 203 patients. The allocation ratio between the two cohorts was 7:3. Based on the independent predictors identified through LASSO regression, the final selection for constructing the prediction model included five variables: lactate, bicarbonate, white blood cell count (WBC), platelet count, and prothrombin time (PT). The nomogram model demonstrated a robust diagnostic ability in both the cohorts used for training and validation. This is supported by the respective area under the curve (AUC) values of 0.843 and 0.891. The results of the calibration curves and HL tests exhibited acceptable conformity between observed and predicted outcomes. According to the DCA analysis, the nomogram model demonstrated a notable overall clinical advantage compared to the APSIII and SAPSII scoring systems. CONCLUSIONS: The nomogram developed during the study proved to be highly accurate in forecasting the mortality of patients with IE during hospitalization in the ICU. As a result, it may be useful for clinicians in decision-making and treatment.

Measured Regional Division Optimization for Acoustic Tomography Velocity Field Reconstruction in a Circular Area.

The acoustic tomography (AT) velocity field reconstruction technique has become a research hotspot in recent years due to its noninvasive nature, high accuracy, and real-time measurement advantages. However, most of the existing studies are limited to the reconstruction of the velocity field in a rectangular area, and there are very few studies on a circular area, mainly because the layout of acoustic transducers, selection of acoustic paths, and division of measured regions are more difficult in a circular area than in a rectangular area. Therefore, based on AT and using the reconstruction algorithm of the Markov function and singular value decomposition (MK-SVD), this paper proposes a measured regional division optimization algorithm for velocity field reconstruction in a circular area. First, an acoustic path distribution based on the multipath effect is designed to solve the problem of the limited emission angle of the acoustic transducer. On this basis, this paper proposes an adaptive optimization algorithm for measurement area division based on multiple sub-objectives. The steps are as follows: first, two optimization objectives, the condition number of coefficient matrix and the uniformity of acoustic path distribution, were designed. Then, the weights of each sub-objective are calculated using the coefficient of variation (CV). Finally, the measured regional division is optimized based on particle swarm optimization (PSO). The reconstruction effect of the algorithm and the anti-interference ability are verified through the reconstruction experiments of the model velocity field and the simulated velocity field.

Impact of open and minimally invasive surgery on postoperative wound complications in patients undergoing prostate surgery: A meta-analysis.

In this article, we analysed the therapeutic efficacy of open radical prostatectomy (ORP) and minimally invasive surgery (MIS) after operation for the treatment of post-operation complications. In summary, because of the broad methodology of the available trials and the low number of trials, the data were limited. The investigators combined the results of six of the 211 original studies. We looked up 4 databases: PubMed, EMBASE, Web of Science and the Cochrane Library. A total of six publications were selected. The main result was the rate of post-operation wound complications. Secondary results were the time of operation and the duration of hospitalization. Our findings indicate that the minimal invasive operation can decrease the incidence of wound infections (OR, 0.61; 95% CI: 0.42,0.90, p = 0.01), bleeding (MD, -293.09; 95% CI: -431.48, -154.71, p < 0.0001), and length of stay in the hospital compared with open surgery (MD, -1.85; 95% CI: -3.52, -0.17, p = 0.03), but minimally invasive surgery increased patient operative time (MD, 51.45; 95% CI: 40.99, 61.92, p < 0.0001). Compared with the open operation, the microinvasive operation has the superiority in the treatment of the wound complications following the operation of radical prostatic carcinoma. But the operation time of the microinvasive operation is much longer. Furthermore, there is a certain amount of bias among the various studies, so it is important to be cautious in interpretation of the findings.

Impact of enhanced recovery after surgery protocols on surgical site wound infection rates in urological procedures.

This meta-analysis assesses the impact of Enhanced Recovery After Surgery (ERAS) protocols on surgical site wound infections (SSWIs) in urological procedures. Analysing data from 10 studies, our focus was on SSWI rates on the third and seventh postoperative days. The results reveal a significant reduction in SSWI rates for patients managed under ERAS protocols compared with traditional care. Notably, Figure 4 demonstrates a substantial decrease in SSWI on the third day (I2 = 93%; random: standardized mean difference [SMD]: -6.25, 95% confidence interval [CI]: -7.42 to -5.05, p < 0.01), and Figure 5 mirrors this trend on the seventh day (I2 = 95%; random: SMD: -4.72, 95% CI: -6.28 to -3.16, p < 0.01). These findings underscore the effectiveness of ERAS protocols in minimizing early postoperative wound infections, emphasizing their importance for broader implementation in urological surgeries.

Deciphering a cell death-associated signature for predicting prognosis and response to immunotherapy in lung squamous cell carcinoma.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell carcinoma, accounting for about 30% of all lung cancers. Yet, the evaluation of prognostic outcome and therapy response of patients with LUSC remains to be resolved. This study aimed to explore the prognostic value of cell death pathways and develop a cell death-associated signature for predicting prognosis and guiding treatment in LUSC. METHODS: Transcriptome profiles and corresponding clinical information of LUSC patients were gathered from The Cancer Genome Atlas (TCGA-LUSC, n = 493) and Gene Expression Omnibus database (GSE74777, n = 107). The cell death-related genes including autophagy (n = 348), apoptosis (n = 163), and necrosis (n = 166) were retrieved from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases. In the training cohort (TCGA-LUSC), LASSO Cox regression was used to construct four prognostic signatures of respective autophagy, apoptosis, and necrosis pathway and genes of three pathways. After comparing the four signatures, the cell death index (CDI), the signature of combined genes, was further validated in the GSE74777 dataset. We also investigated the clinical significance of the CDI signature in predicting the immunotherapeutic response of LUSC patients. RESULTS: The CDI signature was significantly associated with the overall survival of LUSC patients in the training cohort (HR, 2.13; 95% CI, 1.62‒2.82; P < 0.001) and in the validation cohort (HR, 1.94; 95% CI, 1.01‒3.72; P = 0.04). The differentially expressed genes between the high- and low-risk groups contained cell death-associated cytokines and were enriched in immune-associated pathways. We also found a higher infiltration of naive CD4+ T cells, monocytes, activated dendritic cells, neutrophils, and lower infiltration of plasma cells and resting memory CD4+ T cells in the high-risk group. Tumor stemness indices, mRNAsi and mDNAsi, were both negatively correlated with the risk score of the CDI. Moreover, LUSC patients in the low-risk group are more likely to respond to immunotherapy than those in the high-risk group (P = 0.002). CONCLUSIONS: This study revealed a reliable cell death-associated signature (CDI) that closely correlated with prognosis and the tumor microenvironment in LUSC, which may assist in predicting the prognosis and response to immunotherapy for patients with LUSC.

Influence of systolic blood pressure trajectory on in-hospital mortality in patients with sepsis.

BACKGROUND: Numerous studies have investigated the mean arterial pressure in patients with sepsis, and many meaningful results have been obtained. However, few studies have measured the systolic blood pressure (SBP) multiple times and established trajectory models for patients with sepsis with different SBP trajectories. METHODS: Data from patients with sepsis were extracted from the Medical Information Mart for Intensive Care-III database for inclusion in a retrospective cohort study. Ten SBP values within 10 h after hospitalization were extracted, and the interval between each SBP value was 1 h. The SBP measured ten times after admission was analyzed using latent growth mixture modeling to construct a trajectory model. The outcome was in-hospital mortality. The survival probability of different trajectory groups was investigated using Kaplan-Meier (K-M) analysis, and the relationship between different SBP trajectories and in-hospital mortality risk was investigated using Cox proportional-hazards regression model. RESULTS: This study included 3034 patients with sepsis. The median survival time was 67 years (interquartile range: 56-77 years). Seven different SBP trajectories were identified based on model-fit criteria. The in-hospital mortality rates of the patients in trajectory classes 1-7 were 25.5%, 40.5%, 11.8%, 18.3%, 23.5%, 13.8%, and 10.5%, respectively. The K-M analysis indicated that patients in class 2 had the lowest probability of survival. Univariate and multivariate Cox regression analysis indicated that, with class 1 as a reference, patients in class 2 had the highest in-hospital mortality risk (P < 0.001). Subgroup analysis indicated that a nominal interaction occurred between age group and blood pressure trajectory in the in-hospital mortality (P < 0.05). CONCLUSION: Maintaining a systolic blood pressure of approximately 140 mmHg in patients with sepsis within 10 h of admission was associated with a lower risk of in-hospital mortality. Analyzing data from multiple measurements and identifying different categories of patient populations with sepsis will help identify the risks among these categories.

A blessing in disguise-The effect of China's Covid-19 health code system on older people's mobile payment usage.

In early 2020, China launched a health code system to combat the spread of Covid-19. The required health code led to a drastic uptake of smartphone usage among older residents. This paper uses rich commercial data from the Zhejiang Province of China to track the change in consumption among the older population. The paper finds that older people significantly increased spending after switching to mobile payment. The paper contributes to the literature by identifying the unexpected windfall from the effect of the health code mandate on the older population and demonstrating that digital payment works well in the older population.

Biallelic DNAH9 mutations are identified in Chinese patients with defective left-right patterning and cilia-related complex congenital heart disease.

Defective left-right (LR) pattering results in a spectrum of laterality disorders including situs inversus totalis (SIT) and heterotaxy syndrome (Htx). Approximately, 50% of patients with primary ciliary dyskinesia (PCD) displayed SIT. Recessive variants in DNAH9 have recently been implicated in patients with situs inversus. Here, we describe six unrelated family trios and 2 sporadic patients with laterality defects and complex congenital heart disease (CHD). Through whole exome sequencing (WES), we identified compound heterozygous mutations in DNAH9 in the affected individuals of these family trios. Ex vivo cDNA amplification revealed that DNAH9 mRNA expression was significantly downregulated in these patients carrying biallelic DNAH9 mutations, which cause a premature stop codon or exon skipping. Transmission electron microscopy (TEM) analysis identified ultrastructural defects of the outer dynein arms in these affected individuals. dnah9 knockdown in zebrafish lead to the disturbance of cardiac left-right patterning without affecting ciliogenesis in Kupffer's vesicle (KV). By generating a Dnah9 knockout (KO) C57BL/6n mouse model, we found that Dnah9 loss leads to compromised cardiac function. In this study, we identified recessive DNAH9 mutations in Chinese patients with cardiac abnormalities and defective LR pattering.

Soluble Klotho-integrin ß1/ERK1/2 pathway ameliorates myocardial fibrosis in diabetic cardiomyopathy.

Soluble Klotho (sKL) is closely related to insulin resistance, which is a major factor in the progression of diabetic cardiomyopathy (DCM). The purpose of this study was to investigate the role of sKL in the regulation of DCM and the mechanism involved. A mouse model of type 2 diabetes was induced by high-fat diet and streptozotocin injection. An insulin-resistant cardiac fibroblast model was established by high glucose and high insulin. KL gene overexpression was achieved in vivo and vitro through transfection with an adenovirus-harboring KL-cDNA. Gene overexpression was used to evaluate the role of sKL in the pathophysiologic characteristics of DCM. Insulin-resistant cardiac fibroblasts reduced sKL expression and collagen deposition. Diabetic mice constructed by streptozotocin exhibited severe insulin resistance, inflammation, fibrosis, left ventricular dysfunction, and sKL downregulation. The overexpression of sKL mitigated insulin resistance and metabolic disturbance; inflammation, fibrosis, and upregulated collagen I/III content ratio in diabetic state were significantly reduced. Our findings were accompanied by notable moderation of cardiac function. Further, blunted phosphorylation of Akt was restored with sKL gene overexpression, and activated phosphorylation of extracellular signal-regulated kinase 1/2 in DCM was reduced. Our results suggest that sKL protein overexpression exerts a defensive measure by ameliorating selective insulin resistance in mouse DCM, thus revealing its underlying mechanism for potential human DCM treatment.

Association of lactate to albumin ratio and bicarbonate with short-term mortality risk in patients with acute myocardial infarction.

BACKGROUND: Previous studies have indicated that the ratio of lactate/albumin (L/A) has predictive value for the prognosis of critically ill patients with heart failure. Some studies have also indicated that a low serum bicarbonate concentration is inversely related to the mortality risk of patients with cardiogenic shock. However, the value of bicarbonate and the L/A ratio for predicting the mortality risk of patients with acute myocardial infarction (AMI) is still unclear. We therefore conducted a retrospective study to research this problem. METHODS: The subjects of this study were patients with AMI, and the data source was the Medical Information Mart for Intensive Care III database. The primary endpoint was 30-day all-cause mortality after admission. The Receiver operating characteristic (ROC) curve was used to compare the predictive value of L/A ratio, lactate and albumin for end-point events. The effects of different L/A ratio levels and different bicarbonate concentrations on 7-day and 30-day all-cause mortality were compared using Kaplan-Meier (K-M) curves. Hazard ratios for different L/A ratio and different bicarbonate concentrations were investigated using COX proportional hazards models. RESULTS: The Area Under Curve (AUC) of L/A ratio, lactate, and albumin were 0.736, 0.718, and 0.620, respectively. (1) L/A ratio: The patients were divided into three groups according to their L/A ratio: tertile T1 (L/A ratio ≤ 0.47), tertile T2 (L/A ratio ≤ 0.97), and tertile T3 (L/A ratio > 0.97). The T2 and T3 groups had higher 30-day all-cause mortality risks than the T1 group. The restricted cubic spline (RCS) model indicated that there was a nonlinear relationship between L/A ratio and 30-day mortality (P < 0.05). (2) Bicarbonate concentration: The patients were also divided into three groups based on their bicarbonate concentration: G1 (22-27 mmol/L), G2 (< 22 mmol/L), and G3 (> 27 mmol/L). The G2 and G3 groups had higher 30-day all-cause mortality risks than the G1 group. The RCS model indicated that there was a nonlinear relationship between bicarbonate concentration and 30-day mortality (P < 0.05). The RCS model indicated that there was a nonlinear relationship between hemoglobin level and 30-day all-cause mortality (P < 0.05). CONCLUSION: L/A ratio and bicarbonate concentration and hemoglobin level have predictive value for predicting 30-day mortality in patients with acute myocardial infarction.

Biological evaluation of acellular bovine bone matrix treated with NaOH.

We mainly proceed from the view of biological effect to study the acellular bovine bone matrix (ABBM) by the low concentration of hydrogen oxidation. After cleaning the bovine bone routinely, it was cleaned with different concentrations of NaOH and stained with hematoxylin-eosin (HE) to observe the effect of decellulization. The effect of bovine bone matrix treated with NaOH were observed by optical microscopy and scanning electron microscopy (SEM), and compared by DNA residue detection. Cell toxicity was also evaluated in MC3T3-E1 cells by CCK-8. For the in vitro osteogenesis detection, alkaline phosphatase (ALP) staining and alizarin red (AR) staining were performed in MC3T3-E1 cells. And the in vivo experiment, Micro CT, HE and Masson staining were used to observe whether the osteogenic effect of the materials treated with 1% NaOH solution was affected at 6 and 12 weeks. After the bovine bone was decellularized with different concentrations of NaOH solution, HE staining showed that ultrasonic cleaning with 1% NaOH solution for 30 min had the best effect of decellularization. The SEM showed that ABBM treated with 1% NaOH solution had few residual cells on the surface of the three-dimensional porous compared to ABBM treated with conventional chemical reagents. DNA residues and cytotoxicity of ABBM treated with 1% NaOH were both reduced. The results of ALP staining and AR staining showed that ABBM treated with 1% NaOH solution had no effect on the osteogenesis effect. The results of micro-CT, HE staining and Masson staining in animal experiments also showed that ABBM treated with 1% NaOH solution had no effect on the osteogenesis ability. The decellularization treatment of ABBM with the low concentration of NaOH can be more cost-effective, effectively remove the residual cellular components, without affecting the osteogenic ability. Our work may provide a novelty thought and a modified method to applicate the acellular bovine bone matrix clinically better. Graphical abstract.

Rhodium-Catalyzed Aerobic Decomposition of 1,3-Diaryl-2-diazo-1,3-diketones: Mechanistic Investigation and Application to the Synthesis of Benzils.

The conversion of 1,3-diaryl-2-diazo-1,3-diketones to 1,2-daryl-1,2-diketones (benzils) is reported based on a rhodium(II)-catalyzed aerobic decomposition process. The reaction occurs at ambient temperatures and can be catalyzed by a few dirhodium carboxylates (5 mol %) under a balloon pressure of oxygen. Moreover, an oxygen atom from the O2 reagent is shown to be incorporated into the product, and this is accompanied by the extrusion of a carbonyl unit from the starting materials. Mechanistically, it is proposed that the decomposition may proceed via the interaction of a ketene intermediate resulting from a Wolff rearrangement of the carbenoid, with a rhodium peroxide or peroxy radical species generated upon the activation of molecular oxygen. The proposed mechanism has been supported by the results from a set of controlled experiments. By using this newly developed strategy, a large array of benzil derivatives as well as 9,10-phenanthrenequinone were synthesized from the corresponding diazo substrates in varying yields. On the other hand, the method did not allow the generation of benzocyclobutene-1,2-dione from 2-diazo-1,3-indandione because of the difficulty of inducing the initial rearrangement.