Experimental Study on the Fatigue Crack Propagation Rate of 925A Steel for a Ship Rudder System.

The low-temperature fatigue crack propagation rate of 925A steel, as a rudder steel for polar special ships, has a crucial impact on the evaluation of the fatigue strength of polar ships. The purpose of this article is to study the fatigue crack propagation rate of 925A steel under different low-temperature conditions from room temperature (RT) to -60 °C. The material was subjected to fatigue crack propagation tests and stress intensity factor tests. The experimental tests were conducted according to the Chinese Standard of GB/T6398-2017. The results show that as the temperature decreases, the lifespan of 925A increases. Within a certain stress intensity factor, as the temperature decreases, the fatigue crack propagation rate decreases. At -60 °C, it exhibits ductile fracture; within normal polar temperatures, it can be determined that 925A meets the requirements for low-temperature fatigue crack propagation rates in polar regions. However, in some extreme polar temperatures below -60 °C, preventing brittle failure becomes a key focus of fatigue design. Finally, the fatigue crack propagation behavior at the microscale of 925A steel at low temperatures was described using fracture morphology. The experimental data can provide reference for the design of polar ships to further resist low-temperature fatigue and cold brittle fracture.

Post-transplant hepatitis B virus reactivation impacts the prognosis of patients with hepatitis B-related hepatocellular carcinoma: a dual-centre retrospective cohort study in China.

BACKGROUND: Highly active hepatitis B virus (HBV) is known to be associated with poor outcomes in patients with hepatocellular carcinoma (HCC). This study aims to investigate the relationship between HBV status and HCC recurrence after liver transplantation. METHODS: The study retrospectively analyzed HCC patients undergoing liver transplantation in two centres between January 2015 and December 2020. The authors reviewed post-transplant HBV status and its association with outcomes. RESULTS: The prognosis of recipients with hepatitis B surface antigen (HBsAg) reappearance ( n =58) was poorer than those with HBsAg persistent negative ( n =351) and positive ( n =53). In HBsAg persistent positive group, recipients with HBV DNA reappearance or greater than 10-fold increase above baseline had worse outcomes than those without ( P <0.01). HBV reactivation was defined as (a) HBsAg reappearance or (b) HBV DNA reappearance or greater than 10-fold increase above baseline. After propensity score matching, the 5-year overall survival rate and recurrence-free survival rate after liver transplantation in recipients with HBV reactivation were significantly lower than those without (32.0% vs. 62.3%; P <0.01, and 16.4% vs. 63.1%; P <0.01, respectively). Moreover, HBV reactivation was significantly related to post-transplant HCC recurrence, especially lung metastasis. Cox regression analysis revealed that beyond Milan criteria, microvascular invasion and HBsAg-positive graft were independent risk factors for post-transplant HBV reactivation, and a novel nomogram was established accordingly with a good predictive efficacy (area under the time-dependent receiver operating characteristic curve=0.78, C-index =0.73). CONCLUSIONS: Recipients with HBV reactivation had worse outcomes and higher tumour recurrence rates than those without. The nomogram could be used to evaluate the risk of post-transplant HBV reactivation effectively.

Automatic classification of MSA subtypes using Whole-brain gray matter function and Structure-Based radiomics approach.

BACKGROUND: This study aims to develop a radiomics method based on the function and structure of whole-brain gray matter to accurately classify multiple system atrophy with predominant Parkinsonism (MSA-P) or predominant cerebellar ataxia (MSA-C). METHODS: We enrolled 30 MSA-C and 41 MSA-P cases for the internal cohort and 11 MSA-C and 10 MSA-P cases for the external test cohort. We extracted 7,308 features, including gray matter volume (GMV), mean amplitude of low-frequency fluctuation (mALFF), mean regional homogeneity (mReHo), degree of centrality (DC), voxel-mirrored homotopic connectivity (VMHC), and resting-state functional connectivity (RSFC) from 3D-T1 and Rs-fMR data. Feature selection was conducted with t-test and least absolute shrinkage and selection operator (Lasso). Classification was performed using the support vector machine with linear and RBF kernel (SVM-linear/SVM-RBF), random forest and logistic regression. Model performance was assessed via receiver operating characteristic (ROC) curve and compared with DeLong's test. RESULTS: Feature selection resulted in 12 features, including 1 ALFF, 1 DC and 10 RSFC. All the classifiers showed remarkable classification performance, especially the RF model which exhibited AUC values of 0.91 and 0.80 in the validation and test datasets, respectively. The brain functional activity and connectivity in the cerebellum, orbitofrontal lobe and limbic system were important features to distinguish MSA subtypes with the same disease severity and duration. CONCLUSION: Radiomics approach has the potential to support clinical diagnostic systems and to achieve high classification accuracy for distinguishing between MSA-C and MSA-P patients at the individual level.

Alterations of voxel-wise spontaneous activity and corresponding brain functional networks in multiple system atrophy patients with mild cognitive impairment.

Emerging evidence has indicated that cognitive impairment is an underrecognized feature of multiple system atrophy (MSA). Mild cognitive impairment (MCI) is related to a high risk of dementia. However, the mechanism underlying MCI in MSA remains controversial. In this study, we conducted the amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) analyses to detect the characteristics of local neural activity and corresponding network alterations in MSA patients with MCI (MSA-MCI). We enrolled 80 probable MSA patients classified as cognitively normal (MSA-NC, n = 36) and MSA-MCI (n = 44) and 40 healthy controls. Compared with MSA-NC, MSA-MCI exhibited decreased ALFF in the right dorsal lateral prefrontal cortex (RDLPFC) and increased ALFF in the right cerebellar lobule IX and lobule IV-V. In the secondary FC analyses, decreased FC in the left inferior parietal lobe (IPL) was observed when we set the RDLPFC as the seed region. Decreased FC in the bilateral cuneus, left precuneus, and left IPL and increased FC in the right middle temporal gyrus were shown when we set the right cerebellar lobule IX as the seed region. Furthermore, FC of DLPFC-IPL and cerebello-cerebral circuit, as well as ALFF alterations, were significantly correlated with Montreal Cognitive Assessment scores in MSA patients. We also employed whole-brain voxel-based morphometry analysis, but no gray matter atrophy was detected between the patient subgroups. Our findings indicate that altered spontaneous activity in the DLPFC and the cerebellum and disrupted DLPFC-IPL, cerebello-cerebral networks are possible biomarkers of early cognitive decline in MSA patients.

Age-related differences in acute aortic dissection.

OBJECTIVE: The present study investigated the differences in clinical characteristics, treatments, and outcomes of patients with acute aortic dissection (AAD) in different age groups. METHODS: The present single-center retrospective study was conducted from August 2014 to August 2020. The patients were divided into three groups: age <45 years (young group), age 45 to 59 years (middle-age group), and age >59 years (elderly group). Type A (TAAD) and type B (TBAD) aortic dissection were evaluated separately using the latest definitions. RESULTS: The mean age at onset was 52.4 years in our cohort of 602 patients. The young group included a large proportion of male patients (86%). The body mass index and body surface area were higher in the young group. The proportion of non-true lumen blood supply of branches on the abdominal aorta in the young group (27%-55%) was greater than that in the others. In the young group, the distal extent of dissection in 84% of TAAD and 89% of TBAD exceeded the abdominal aortic branch cluster (AABC) compared with 36% of TAAD and 58% of TBAD in the elderly group. The multivariate analysis revealed that age <45 years (odds ratio, 5.15; P < .001) and D-dimer level (odds ratio, 1.05; P = .001) were risk factors for intimal flap tear exceeding the AABC. The proportion of visceral and lower limb malperfusion increased from 4.8% to 36.9% as the intimal flap tear exceeded the AABC. CONCLUSIONS: Compared with middle-age and elderly patients, young patients with AAD had two characteristics (ie, obesity and an intimal flap that had frequently exceeded the branches of the aorta). These two factors resulted in a greater proportion of non-true lumen blood supply, increased visceral and lower limb malperfusion, and an increase in potential associated risks.

Fungal cellulases: protein engineering and post-translational modifications.

Enzymatic degradation of lignocelluloses into fermentable sugars to produce biofuels and other biomaterials is critical for environmentally sustainable development and energy resource supply. However, there are problems in enzymatic cellulose hydrolysis, such as the complex cellulase composition, low degradation efficiency, high production cost, and post-translational modifications (PTMs), all of which are closely related to specific characteristics of cellulases that remain unclear. These problems hinder the practical application of cellulases. Due to the rapid development of computer technology in recent years, computer-aided protein engineering is being widely used, which also brings new opportunities for the development of cellulases. Especially in recent years, a large number of studies have reported on the application of computer-aided protein engineering in the development of cellulases; however, these articles have not been systematically reviewed. This article focused on the aspect of protein engineering and PTMs of fungal cellulases. In this manuscript, the latest literatures and the distribution of potential sites of cellulases for engineering have been systematically summarized, which provide reference for further improvement of cellulase properties. KEY POINTS: •Rational design based on virtual mutagenesis can improve cellulase properties. •Modifying protein side chains and glycans helps obtain superior cellulases. •N-terminal glutamine-pyroglutamate conversion stabilizes fungal cellulases.

Use of machine learning method on automatic classification of motor subtype of Parkinson's disease based on multilevel indices of rs-fMRI.

OBJECTIVE: This study aimed to develop an automatic classifier to distinguish different motor subtypes of Parkinson's disease (PD) based on multilevel indices of resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Ninety-six PD patients, which included thirty-nine postural instability and gait difficulty (PIGD) subtype and fifty-seven tremor-dominant (TD) subtype, were enrolled and allocated to training and validation datasets with a ratio of 7:3. A total of five types of index, consisting of mean regional homogeneity (mReHo), mean amplitude of low-frequency fluctuation (mALFF), degree of centrality (DC), voxel-mirrored homotopic connectivity (VMHC), and functional connectivity (FC), were extracted. The features were then selected using a two-sample t-test, the least absolute shrinkage and selection operator (LASSO), and Spearman's rank correlation coefficient. Finally, support vector machine (SVM) models based on the separate index and multilevel indices were built, and the performance of models was assessed via the area under the receiver operating characteristic curve (AUC). Feature importance was evaluated using Shapley additive explanation (SHAP) values. RESULTS: The optimal SVM model was obtained based on multilevel rs-fMRI indices, with an AUC of 0.934 in the training dataset and an AUC of 0.917 in the validation dataset. The AUCs of the models based on the separate index were ranged from 0.783 to 0.858 for the training dataset and from 0.713 to 0.792 for the validation dataset. SHAP analysis revealed that functional activity and connectivity in frontal lobe and cerebellum were important features for differentiating PD subtypes. CONCLUSIONS: Our findings demonstrated multilevel rs-fMRI indices could provide more comprehensive information on brain functionalteration. Furthermore, the machine learning method based on multilevel rs-fMRI indices might be served as an alternative approach for automatically classifying clinical subtypes in PD at the individual level.

Morphological Changes in Cortical and Subcortical Structures in Multiple System Atrophy Patients With Mild Cognitive Impairment.

OBJECTIVE: This study aimed to investigate the morphometric alterations in the cortical and subcortical structures in multiple system atrophy (MSA) patients with mild cognitive impairment (MCI), and to explore the association with cognitive deficits. METHODS: A total of 45 MSA patients (25 MSA-only, 20 MSA-MCI) and 29 healthy controls were recruited. FreeSurfer software was used to analyze cortical thickness, and voxel-based morphometry was used to analyze the gray matter volumes. Cortical thickness and gray matter volume changes were correlated with cognitive scores. RESULTS: Compared to healthy controls, both MSA subgroups exhibited widespread morphology alterations of brain structures in the fronto-temporal regions. Direct comparison of MSA-MCI and MSA-only patients showed volume reduction in the left superior and middle temporal gyrus, while cortical thinning was found in the left middle and inferior temporal gyrus in MSA-MCI patients. Cortical thinning in the left middle temporal gyrus correlated with cognitive assessment and disease duration. CONCLUSION: Structural changes in the brain occur in MSA-MCI patients. The alteration of brain structure in the left temporal regions might be a biomarker of cognitive decline in MSA-MCI patients.

Enzyme cascade for biocatalytic deracemization of D,L-phosphinothricin.

Deracemization of D,L-phosphinothricin (D,L-PPT) is one of the most promising routes for preparation of optically pure L-PPT. In this work, an efficient multi-enzyme redox cascade was developed for deracemization ofPPT, which includes oxidative reaction and reductive reaction. The oxidative reaction catalyzing oxidative deamination of D-PPT to 2-oxo-4-[(hydroxy)(-methyl)phosphinyl]butyric acid (PPO) was performed by a D-amino acid oxidase and a catalase for removing H2O2. The reductive reaction catalyzing amination of PPO to L-PPT is achieved by a glufosinate dehydrogenase and a glucose dehydrogenase for cofactor regeneration. To avoid the inhibitory effect of glucose on the oxidative reaction, a "two stages in one-pot" strategy was developed to combine these two reactions in deracemization process. By using this strategy, the L-PPT was obtained with a high yield (89 %) and > 99 % enantiomeric excess at substrate loading of 300 mM in absence of addition of extra NADP+. These encouraging results demonstrated that the developed enzyme cascade deracemization process exhibits great potential and economical competitiveness for manufacture of L-PPT from D,L-PPT.

Alterations in Degree Centrality and Functional Connectivity in Parkinson's Disease Patients With Freezing of Gait: A Resting-State Functional Magnetic Resonance Imaging Study.

OBJECTIVE: Freezing of gait (FOG) is a common disabling motor symptom in Parkinson's disease (PD), but the potential pathogenic mechanisms are still unclear. METHODS: A total of 22 patients with PD with FOG (PD-FOG), 28 patients with PD without FOG (PD-nFOG), and 33 healthy controls (HCs) were recruited in this study. Degree centrality (DC)-a graph theory-based measurement of global connectivity at the voxel level by measuring the number of instantaneous functional connections between one region and the rest of the brain-can map brain hubs with high sensitivity, specificity, and reproducibility. DC was used to explore alterations in the centrality of PD-FOG correlated with brain node levels. PD-FOG cognitive network dysfunction was further revealed via a seed-based functional connectivity (FC) analysis. In addition, correlation analyses were carried out between clinical symptoms and acquired connectivity measurement. RESULTS: Compared to the PD-nFOG group, the PD-FOG group showed remarkably increased DC values in the right middle frontal gyrus (RMFG). There were no significant differences in other gray matter regions. Importantly, the clinical severity of FOG was related to the mean DC values in the RMFG. This brain region served as a seed in secondary seed-based FC analysis, and we further found FC changes in the right precuneus, right inferior frontal gyrus, right superior frontal gyrus (SFG), and cerebellum. CONCLUSION: Increased RMFG activity and FC network alterations in the middle frontal cortex with the precuneus, inferior, and SFG, and the cerebellum may have great potential in brain dysfunction in PD with FOG.

Efficient synthesis of L-phosphinothricin using a novel aminoacylase mined from Stenotrophomonas maltophilia.

L-phosphinothricin (L-PPT) is a competitive and environmentally friendly herbicide. To develop an efficient approach for synthesis of l-PPT, a kinetic resolution route with a novel aminoacylase (SmAcy) mined from Stenotrophomonas maltophilia using N-acetyl-PPT as a substrate was first constructed. This SmAcy exhibited high hydrolytic activity and excellent enantioselectivity (E > 200) toward N-acetyl-PPT. Optically pure l-PPT (> 99.9 % eep) was acquired with high conversion (> 49 %) within 4 h by the whole cells. On the basis of the docking analysis, a main reason for high enantioselectivity (E > 200) of SmAcy towards l-enantiomer would be that the D-N-acetyl-PPT cannot interact with the key general acid-base residue and the metal ions. A low-cost and simple preparation process of the substrate from commercially available racemic PPT for production of L-PPT was provided. A chemical racemization method of the unreacted D-enantiomer of substrate was also provided to recycle the unwanted substrate enantiomer. This study provides a potential route for the industrial production of L-PPT.

Altered resting-state voxel-level whole-brain functional connectivity in multiple system atrophy patients with cognitive impairment.

OBJECTIVE: There is increasing evidence of cognitive impairment (CI) frequently occurring in patients with multiple system atrophy (MSA); however, the neurobiological mechanisms underlying CI in patients with MSA remain unclear. METHODS: We enrolled 61 patients with probable MSA and 33 healthy controls (HC). We used degree centrality (DC) analysis to assess changes in the centrality level of MSA-CI related brain nodes. We conducted a secondary seed-based functional connectivity (FC) analysis to investigate dysfunctions in cognitive networks related to MSA. Further, we analysed the correlation between clinical symptoms and acquired connectivity measures. RESULTS: Compared with HC, patients with MSA-CI and those with MSA with normal cognition (MSA-NCI) exhibited lower DC values in the left calcarine and right postcentral regions and higher DC values in the bilateral caudate and left precuneus. There were significant differences in the DC values in the right middle prefrontal gyrus between the MSA-CI and MSA-NCI groups. The mean DC values in the right middle prefrontal gyrus (RMPFG) were correlated with clinical cognitive severity. Consequently, we used this brain region as a seed in secondary seed-based FC analysis and observed FC changes within the right precuneus, inferior parietal lobe, and right insula. CONCLUSIONS: Decreased middle prefrontal cortex activity and its altered functional connectivity with the precuneus, inferior parietal lobe, and insula are possible biomarkers of cognitive dysfunction in patients with MSA-CI. SIGNIFICANCE: Cognitive impairment in MSA is associated with alterations in the dorsolateral prefrontal cortex network.

Enzymatic asymmetric synthesis of chiral amino acids.

Chiral amino acids are extensively applied in the pharmaceutical, food, cosmetic, agricultural, and feedstuff industries. The development of synthetic methodologies for optically pure amino acids has been driven by their significant applications. Among the various synthesis methods for the production of chiral amino acids, enzymatic asymmetric synthesis is a unique preparation strategy that shows great potential. This review provides an overview of the reported methods for enzymatic asymmetric synthesis of chiral amino acids, including asymmetric reductive amination of keto acids, asymmetric transfer of an amino group to keto acids, enantioselective addition of ammonia to α,ß-unsaturated acids, and aldol condensation of an amino acid to aldehydes.

Ag-bridged Ag2O nanowire network/TiO2 nanotube array p-n heterojunction as a highly efficient and stable visible light photocatalyst.

A unique Ag-bridged Ag2O nanowire network/TiO2 nanotube array p-n heterojunction (Ag-Ag2O/TiO2 NT) was fabricated by simple electrochemical method. Ag nanoparticles were firstly electrochemically deposited onto the surface of TiO2 NT and then were partly oxidized to Ag2O nanowires while the rest of Ag mother nanoparticles were located at the junctions of Ag2O nanowire network. The Ag-Ag2O/TiO2 NT heterostructure exhibited strong visible-light response, effective separation of photogenerated carriers, and high adsorption capacity. The integration of Ag-Ag2O self-stability structure and p-n heterojunction permitted high and stable photocatalytic activity of Ag-Ag2O/TiO2 NT heterostructure photocatalyst. Under 140-min visible light irradiation, the photocatalytic removal efficiency of both dye acid orange 7 (AO7) and industrial chemical p-nitrophenol (PNP) over Ag-Ag2O/TiO2 NT reached nearly 100% much higher than 17% for AO7 or 13% for PNP over bare TiO2 NT. After 5 successive cycles under 600-min simulated solar light irradiation, Ag-Ag2O/TiO2 NT remained highly stable photocatalytic activity.