The Risk of and Associated Demographic and Laboratory Variables for Amputations for Inpatients with Diabetic Foot Ulcers.

OBJECTIVE: Diabetic foot ulcers (DFUs) are a leading cause of morbidity and mortality, which disproportionately impacts underserved populations. This study aimed to provide data regarding the rates and outcomes of amputation in patients admitted with DFU in our health system, which cares for an ethnically diverse and underserved population. METHODS: This retrospective study examined the electronic medical records of adult patients hospitalized with DFU at 3 hospitals in our health system between June 1, 2016, and May 31, 2021. RESULTS: Among 650 patients admitted with DFU, 88% self-identified as non-White race. Male sex (odds ratio [OR], 0.62), low body mass index (OR, 0.98), and history of smoking (OR, 1.45) were significantly associated with amputation during the study period. A higher erythrocyte sedimentation rate (OR, 1.01), C-reactive protein level (OR, 1.05), and white blood cell count (OR, 1.11) and low albumin level (OR, 0.41) were found to be significantly associated with amputation versus no amputation during admission. The amputation risk during the index admission for DFU was 44%. CONCLUSION: Our study identified a high DFU-related amputation risk (44%) among adult patients who were mostly Black and/or Hispanic. The significant risk factors associated with DFU amputation included male sex, low body mass index, smoking, and high levels inflammation or low levels of albumin during admission. Many of these patients required multidisciplinary care and intravenous antibiotic therapy, necessitating a longer length of stay and high readmission rate.

Toward Earth system modeling with resolved clouds and ocean submesoscales on heterogeneous many-core HPCs.

With the aid of the newly developed 'Sunway' heterogeneous-architecture supercomputer, which has world-leading HPC (high-performance computer) capability, a series of high-resolution coupled Earth system models (SW-HRESMs) with up to 5 km of atmosphere and 3 km of ocean have been developed. These models can meet the needs of multiscale interaction studies with different computational costs. Here we describe the progress of SW-HRESMs development, with an overview of the major advancements made by the international Earth science community in HR-ESMs. We also show the preliminary results of SW-HRESMs with regard to capturing major weather-climate extremes in the atmosphere and ocean, stressing the importance of permitted clouds and ocean submesoscale eddies in modeling tropical cyclones and eddy-mean flow interactions, and paving the way for further model development to resolve finer scales with even higher resolution and more realistic physics. Finally, in addition to increasing model resolution, the development procedure for a non-hydrostatic cloud and ocean submesoscale resolved ESM is discussed, laying out the major scientific directions of such a huge modeling advancement.

Development and validation of a prediction equation for body fat percentage from measured BMI: a supervised machine learning approach.

Body mass index is a widely used but poor predictor of adiposity in populations with excessive fat-free mass. Rigorous predictive models validated specifically in a nationally representative sample of the US population and that could be used for calibration purposes are needed. The objective of this study was to develop and validate prediction equations of body fat percentage obtained from Dual Energy X-ray Absorptiometry using body mass index (BMI) and socio-demographics. We used the National Health and Nutrition Examination Survey (NHANES) data from 5931 and 2340 adults aged 20 to 69 in 1999-2002 and 2003-2006, respectively. A supervised machine learning using ordinary least squares and a validation set approach were used to develop and select best models based on R2 and root mean square error. We compared our findings with other published models and utilized our best models to assess the amount of bias in the association between predicted body fat and elevated low-density lipoprotein (LDL). Three models included BMI, BMI2, age, gender, education, income, and interaction terms and produced R-squared values of 0.87 and yielded the smallest standard errors of estimation. The amount of bias in the association between predicted BF% and elevated LDL from our best model was -0.005. Our models provided strong predictive abilities and low bias compared to most published models. Its strengths rely on its simplicity and its ease of use in low-resource settings.

Energetic evaluation of phenol wastewater treatment by reverse electrodialysis reactor using different anodes.

Efficient electrode materials are essential to convert salinity gradient energy into oxidative degradation energy and electrical energy by reverse electrodialysis reactor (REDR). In this context, comparative experiments of REDR using different anodes (Ti/IrO2-RuO2, Ti/PbO2 and Ti/Ti4O7) were conducted. The effects of output current and electrode rinse solution (ERS) flowrate on mineralization efficiency and energy output were discussed. Results demonstrated that the COD removal rate(ηCOD) rose almost linearly with output current and ERS flowrate when using Ti/Ti4O7 anode, but excessive operating conditions caused a slow increase or even decrease of ηCOD when using Ti/IrO2-RuO2 or Ti/PbO2 anodes. The order of electrode system potential loss (Eele) for the three anodes was Ti/Ti4O7> Ti/PbO2> Ti/IrO2-RuO2. High Eele was beneficial to ηCOD but had a negative effect on the net output power (Pnet) of REDR. Regardless of the applied anodes, increasing the current and decreasing the ERS flowrate was detrimental to Pnet due to higher Eele. Based on these findings, four energy efficiency parameters were defined to evaluate energy recovery from multiple perspectives by linking energy output with mineralization capacity. They were electrode efficiency (ηele), energy efficiency (EE), general current efficiency (GCE) and energy consumption (EC), respectively. Results showed that REDR with Ti/Ti4O7 anodes and suitable operating conditions achieved the optimal energy indicators and mineralization efficiency, which provided an efficient and economical option for wastewater treatment and energy recovery.

State of Health Estimation Based on the Long Short-Term Memory Network Using Incremental Capacity and Transfer Learning.

Battery state of health (SOH) estimating is essential for the safety and preservation of electric vehicles. The degradation mechanism of batteries under different aging conditions has attracted considerable attention in SOH prediction. In this article, the discharge voltage curve early in the cycle is considered to be strongly characteristic during cell aging. Therefore, the battery aging state can be quantitatively characterized by an incremental capacity analysis (ICA) of the voltage distribution. Due to the interference of vibration noise of the test platform, the discrete wavelet transform (DWT) methods are accustomed to soften the premier incremental capacity curves in different hierarchical decompositions. By analyzing the battery aging mechanism, the peak of the curve and its corresponding voltage are used in the characterization of capacity decay by grey relation analysis (GRA) and to optimize the input of the deep learning model, and finally, the double-layer long short-term memory network (LSTM) model is used to train the data. The results demonstrate that the proposed model can predict the SOH of a single battery cycle using only small batch data and the relative error is less than 2%. Further, by freezing the LSTM layer for transfer learning, it can be used for battery health estimation in different loading modes. The results of training and verification show that this method has high accuracy and reliability in SOH estimation.

Electrochemical removal of synthetic methyl orange dyeing wastewater by reverse electrodialysis reactor: Experiment and mineralizing model.

In this paper, the synthetic methyl orange (MO) dyeing wastewater treated by a reverse electrodialysis reactor (REDR) with 40 member pairs was investigated first. The boron-doped diamond (BDD) and carbon felt were adopted as an anode and a cathode in the REDR. The influences of operation parameters on the chemical oxygen demand (COD) removal efficiency were detected and explored. Then, a mathematical model of organic mineralizing was developed for the REDR to predict the variation of COD removal efficiency with treating time under the different operation conditions. Finally, the energy consumption of the wastewater treated by the REDR was analyzed. The results showed that raising the working fluid flowing velocity and electrode rinse solution flowrate improved the COD removal efficiency and instantaneous current efficiency (ICE), and reduced the total energy consumption (TEC) of the REDR. Raising the initial MO concentration could significantly reduce the TEC despite the COD removal efficiency being near. Since the main energy consumed by the REDR was salinity gradient energy (SGE) from waste heat conversion or the natural environment, the energy cost of REDR treating wastewater has been reduced significantly.

Target residence of Cas9-sgRNA influences DNA double-strand break repair pathway choices in CRISPR/Cas9 genome editing.

BACKGROUND: Due to post-cleavage residence of the Cas9-sgRNA complex at its target, Cas9-induced DNA double-strand breaks (DSBs) have to be exposed to engage DSB repair pathways. Target interaction of Cas9-sgRNA determines its target binding affinity and modulates its post-cleavage target residence duration and exposure of Cas9-induced DSBs. This exposure, via different mechanisms, may initiate variable DNA damage responses, influencing DSB repair pathway choices and contributing to mutational heterogeneity in genome editing. However, this regulation of DSB repair pathway choices is poorly understood. RESULTS: In repair of Cas9-induced DSBs, repair pathway choices vary widely at different target sites and classical nonhomologous end joining (c-NHEJ) is not even engaged at some sites. In mouse embryonic stem cells, weakening the target interaction of Cas9-sgRNA promotes bias towards c-NHEJ and increases target dissociation and reduces target residence of Cas9-sgRNAs in vitro. As an important strategy for enhancing homology-directed repair, inactivation of c-NHEJ aggravates off-target activities of Cas9-sgRNA due to its weak interaction with off-target sites. By dislodging Cas9-sgRNA from its cleaved targets, DNA replication alters DSB end configurations and suppresses c-NHEJ in favor of other repair pathways, whereas transcription has little effect on c-NHEJ engagement. Dissociation of Cas9-sgRNA from its cleaved target by DNA replication may generate three-ended DSBs, resulting in palindromic fusion of sister chromatids, a potential source for CRISPR/Cas9-induced on-target chromosomal rearrangements. CONCLUSIONS: Target residence of Cas9-sgRNA modulates DSB repair pathway choices likely through varying dissociation of Cas9-sgRNA from cleaved DNA, thus widening on-target and off-target mutational spectra in CRISPR/Cas9 genome editing.

Prussian Blue Type Cocatalysts for Enhancing the Photocatalytic Water Oxidation Performance of BiVO4.

The efficiency of photocatalytic overall water splitting reactions is usually limited by the high energy barrier and complex multiple electron-transfer processes of the oxygen evolution reaction (OER). Although bismuth vanadate (BiVO4 ) as the photocatalyst has been developed for enhancing the kinetics of the water oxidation reaction, it still suffers from challenges of fast recombination of photogenerated electron-hole pairs and poor photocatalytic activity. Herein, six MII -CoIII Prussian blue analogues (PBAs) (M=Mn, Fe, Co, Ni, Cu and Zn) cocatalysts are synthesized and deposited on the surface of BiVO4 for boosting the surface catalytic efficiency and enhancing photogenerated carries separation efficiency of BiVO4 . Six MII -CoIII PBAs@BiVO4 photocatalysts all demonstrate increased photocatalytic water oxidation performance compared to that of BiVO4 alone. Among them, the Co-Co PBA@BiVO4 photocatalyst is employed as a representative research object and is thoroughly characterized by electrochemistry, electronic microscope as well as multiple spectroscopic analyses. Notably, BiVO4 coupling with Co-Co PBA cocatalyst could capture more photons than that of pure BiVO4 , facilitating the transfer of photogenerated charge carriers between BiVO4 and Co-Co PBA as well as the surface catalytic efficiency of BiVO4 . Overall, this work would promote the synthesis strategy development for exploring new types of composite photocatalysts for water oxidation.

Ir-Catalyzed Asymmetric Tandem Allylation/Iso-Pictet-Spengler Cyclization Reaction for the Enantioselective Construction of Tetrahydro-γ-carbolines.

Ir-catalyzed asymmetric tandem allylation/iso-Pictet-Spengler cyclization of arylidenaminomalonates with indolyl allylic methyl carbonates was successfully developed, which provided a direct and practical approach to access synthetically useful and biologically active tetrahydro-γ-carboline derivatives bearing multiple functional groups and stereogenic centers in good to high yields and excellent stereoselective control (44%-96% yields, >20:1 dr, 94% → 99% ee). A wide range of substrate generality, easily available substrates, and simple chiral catalytic system displayed great potential practicality of this efficient protocol.

A new entry to highly functionalized pyrroles via a cascade reaction of α-amino esters and alkynals.

Here, we developed an expedient access route to highly functionalized pyrroles from readily available α-amino acid ester hydrochlorides and alkynals via a cascade condensation/intramolecular cyclization followed by a unique C-N ester migration process. A variety of 1,2,3-trisubstituted pyrroles, which were difficult to acquire with the common methodologies, were successfully prepared in good yields under mild conditions.

Asymmetric synthesis of quaternary α-trifluoromethyl α-amino acids by Ir-catalyzed allylation followed by kinetic resolution.

Facile access to quaternary α-trifluoromethyl α-amino acids has been developed. This sequential reaction involves an Ir-catalyzed asymmetric allylation of α-trifluoromethyl aldimine esters followed by an unprecedented kinetic resolution.

Fluoride in tea from Shandong Province, China and exposure assessment.

In this study fluoride in 170 tea samples from Shandong province (China) was determined using a selective ion electrode. The fluoride concentrations ranged from 31.2 to 338 mg/kg with an average of 119 mg/kg. The mean fluoride concentrations were 164, 121, 98.7 and 96.8 mg/kg, which corresponded to Pu'erh tea, green tea, oolong tea and black tea, respectively. Moreover, 4.7% of the analysed samples exceed the legal limit of 200 mg/kg recommended by China. The estimated daily intake of fluoride via drinking tea for an adult was between 0.655 and 1.07 mg/person/day, which were lower than the provisional maximum tolerable daily intake value of 3.5 mg/person/day set by the National Health and Family Planning Commission of the People's Republic of China. In future, maintaining a surveillance programme to monitor the trend of fluoride in tea is necessary for food safety and human health.

Atg11 is required for initiation of glucose starvation-induced autophagy.

How energy deprivation induces macroautophagy/autophagy is not fully understood. Here, we show that Atg11, a receptor protein for cargo recognition in selective autophagy, is required for the initiation of glucose starvation-induced autophagy. Upon glucose starvation, Atg11 facilitates the interaction between Snf1 and Atg1, thus is required for Snf1-dependent Atg1 activation. Phagophore assembly site (PAS) formation requires Atg11 via its control of the association of Atg17 with Atg29-Atg31. The binding of Atg11 with Atg9 is crucial for recruiting Atg9 vesicles to the PAS and, thus, glucose starvation-induced autophagy. We propose Atg11 as a key initiation factor controlling multiple key steps in energy deprivation-induced autophagy. Abbreviations: AMPK: AMP-activated protein kinase; Ams1: α-mannosidase; Ape1: aminopeptidase I; Cvt: cytoplasm-to-vacuole targeting; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; GFP: green fluorescent protein; MBP: myelin basic protein; MMS: methanesulfonate; PAS: phagophore assembly site; PNBM: p-nitrobenzyl mesylate; SD-G: glucose starvation medium; SD-N: nitrogen starvation medium; ULK1, unc-51 like autophagy activating kinase 1; WT: wild type.

Stereodivergent assembly of tetrahydro-γ-carbolines via synergistic catalytic asymmetric cascade reaction.

Enantiomerically enriched indole-containing heterocycles play a vital role in bioscience, medicine, and chemistry. As one of the most attractive subtypes of indole alkaloids, highly substituted tetrahydro-γ-carbolines are the basic structural unit in many natural products and pharmaceuticals. However, the syntheses of tetrahydro-γ-carbolines with high functionalities from readily available reagents are significant challenging. In particular, the stereodivergent syntheses of tetrahydro-γ-carbolines containing multi-stereogenic centers remain quite difficult. Herein, we report an expedient and stereodivergent assembly of tetrahydro-γ-carbolines with remarkably high levels of stereoselective control in an efficient cascade process from aldimine esters and indolyl allylic carbonates via a synergistic Cu/Ir catalyst system. Control experiments-guided optimization of synergistic catalysts and mechanistic investigations reveal that a stereodivergent allylation reaction and a subsequent highly stereoselective iso-Pictet-Spengler cyclization are the key elements to success.

Clinical application value of brain CT perfusion imaging in the treatment of acute ischemic stroke thrombolytic therapy.

Clinical application value of CT perfusion (CTP) imaging in the treatment of acute ischemic stroke (AIS) thrombolytic therapy was investigated. Retrospective analysis of 185 suspected AIS patients in Liaocheng Brain Hospital from April 2012 to December 2017 were involved. We observed the non-contrast CT (NCCT) and CTP in the diagnosis of AIS patients, and recorded as well as compared CTP parameters of AIS patients. The National Institute of Health Stroke Scale (NIHSS) rating was conducted, and the correlation between the prognosis of NIHSS scores and CTP parameters was investigated. A total of 177 patients were diagnosed with AIS. The sensitivity levels of CTP examination for diagnosis of AIS patients was significantly higher than that of the NCCT examination (P<0.050). The diagnostic compliance rates of CTP examination was significantly higher than that of the NCCT examination (P<0.050). The cerebral blood volume (CBV) in the abnormal perfusion area was significantly lower than that in the mirror side zone (t=21.160, P<0.001). The prognostic NIHSS score was negatively correlated with CBV in patients with thrombolytic therapy (r=-0.912, P<0.001). The cerebral blood flow (CBF) in the abnormal perfusion zone was significantly lower than that in the mirror side zone (t=19.170, P<0.001). The prognosis of patients with thrombolytic therapy was negatively correlated with CBF (r=-0.915, P<0.001). The mean transit time (MTT) in the abnormal perfusion zone was higher than that in the mirror side zone (t=13.480, P<0.001). NIHSS scores were obtained 3 months after thrombolytic therapy and found that the prognostic NIHSS scores were positively correlated with MTT (r=0.887, P<0.001). The results indicated that brain CTP has a high diagnostic value for intravenous thrombolytic therapy in AIS and there was a significant correlation between the prognosis scores of patients. Thus, it is worthy of being promoted in the clinical diagnosis and treatment of AIS patients.

Apelin Ameliorates High Glucose-Induced Downregulation of Connexin 43 via AMPK-Dependent Pathway in Neonatal Rat Cardiomyocytes.

Diabetes Mellitus is a common disorder, with increasing risk of cardiac arrhythmias. Studies have shown that altered connexin expression and gap junction remodeling under hyperglycemia contribute to the high prevalence of cardiac arrhythmias and even sudden death. Connexin 43 (Cx43), a major protein that assembles to form cardiac gap junctions, has been found to be downregulated under high glucose conditions, along with inhibition of gap junctional intercellular communication (GJIC). While, apelin, a beneficial adipokine, increases Cx43 protein expression in mouse and human embryonic stem cells during cardiac differentiation. However, it remains unknown whether apelin influences GJIC capacity in cardiomyocytes. Here, using Western blotting and dye transfer assays, we found that Cx43 protein expression was reduced and GJIC was impaired after treatment with high glucose, which, however, could be abrogated after apelin treatment for 48 h. We also found that apelin increased Cx43 expression under normal glucose. Real-time PCR showed that the Cx43 mRNA was not significantly affected under high glucose conditions in the presence of apelin or high glucose and apelin. High glucose decreased the phosphorylation of AMPKα; however, apelin activated AMPKα. Interestingly, we found that Cx43 expression was increased after treatment with AICAR, an activator of AMPK signaling. AMPKα inhibition mediated with transfection of siRNA-AMPKα1 and siRNA-AMPKα2 abolished the protective effect of apelin on Cx43 expression. Our data suggest that apelin attenuates high glucose-induced Cx43 downregulation and improves the loss of functional gap junctions partly through the AMPK pathway.

An approach to localization for ensemble-based data assimilation.

Localization techniques are commonly used in ensemble-based data assimilation (e.g., the Ensemble Kalman Filter (EnKF) method) because of insufficient ensemble samples. They can effectively ameliorate the spurious long-range correlations between the background and observations. However, localization is very expensive when the problem to be solved is of high dimension (say 106 or higher) for assimilating observations simultaneously. To reduce the cost of localization for high-dimension problems, an approach is proposed in this paper, which approximately expands the correlation function of the localization matrix using a limited number of principal eigenvectors so that the Schür product between the localization matrix and a high-dimension covariance matrix is reduced to the sum of a series of Schür products between two simple vectors. These eigenvectors are actually the sine functions with different periods and phases. Numerical experiments show that when the number of principal eigenvectors used reaches 20, the approximate expansion of the correlation function is very close to the exact one in the one-dimensional (1D) and two-dimensional (2D) cases. The new approach is then applied to localization in the EnKF method, and its performance is evaluated in assimilation-cycle experiments with the Lorenz-96 model and single assimilation experiments using a barotropic shallow water model. The results suggest that the approach is feasible in providing comparable assimilation analysis with far less cost.

Stereodivergent Synthesis of α,α-Disubstituted α-Amino Acids via Synergistic Cu/Ir Catalysis.

Cu/Ir dual catalysis has been developed for the stereodivergent α-allylation of aldimine esters. The method enables the preparation of a series of nonproteinogenic α-amino acids (α-AAs) bearing two contiguous stereogenic centers in high yield with excellent stereoselectivity. All four product stereoisomers could be obtained from the same set of starting materials via pairwise combination of two chiral catalysts. Notably, one-pot protocol could be successfully applied for the preparation of the bimetallic Cu/Ir complexes to simplify the manipulation of Cu/Ir dual catalysis. This method could be further utilized for the construction of the key intermediate of a bioactive pyrrolidine derivative and the concise synthesis of a plant growth regulator (2S,3S)-2-amino-3-cyclopropylbutanoic acid.

Expression of key enzymes in the mevalonate pathway are altered in monocrotaline-induced pulmonary arterial hypertension in rats.

Pulmonary arterial hypertension (PAH) is a serious pulmonary vascular disease. The changes in the structure, function and metabolism of endothelial cells are some of the important features of PAH. Previous studies have demonstrated that the mevalonate pathway is important in cardiovascular remodeling. However, whether the mevalonate pathway is involved in the development of PAH remains to be elucidated. The present study aimed to investigate the expression pattern of mevalonate pathway-related enzymes in monocrotaline (MCT)-induced PAH. F344 rats were randomly divided into two groups (n=6/group): Control group rats were injected with a single dose of saline, and MCT group rats were injected with a single dose of MCT (60 mg/kg). After 4 weeks, the right ventricular systolic pressure (RVSP) was measured, and lung and pulmonary artery tissue samples were collected. It was demonstrated that the RVSP increased and pulmonary vascular remodeling was detected in the PAH group. The expression levels of the enzymes farnesyldiphosphate synthase farnesyltransferase α and geranylgeranyltransferase type I increased in the PAH group, which suggested that the mevalonate pathway may be involved in the pathological development of PAH.

Synergistic Cu/Pd Catalysis for Enantioselective Allylic Alkylation of Aldimine Esters: Access to α,α-Disubstituted α-Amino Acids.

An unprecedented enantioselective allylic alkylation of readily available aldimine esters has been developed, and is catalyzed by a synergistic Cu/Pd catalyst system. This strategy provides facile access to nonproteinogenic α,α-disubstituted α-amino acids in high yield with excellent enantioselectivity. The more challenging double allylic alkylation of glycinate-derived imine esters was also realized. Furthermore, this methodology was applied for the construction of the key intermediate of PLG peptidomimetics.