REME: an integrated platform for reaction enzyme mining and evaluation.

A key challenge in pathway design is finding proper enzymes that can be engineered to catalyze a non-natural reaction. Although existing tools can identify potential enzymes based on similar reactions, these tools encounter several issues. Firstly, the calculated similar reactions may not even have the same reaction type. Secondly, the associated enzymes are often numerous and identifying the most promising candidate enzymes is difficult due to the lack of data for evaluation. Thirdly, existing web tools do not provide interactive functions that enable users to fine-tune results based on their expertise. Here, we present REME (https://reme.biodesign.ac.cn/), the first integrated web platform for reaction enzyme mining and evaluation. Combining atom-to-atom mapping, atom type change identification, and reaction similarity calculation enables quick ranking and visualization of reactions similar to an objective non-natural reaction. Additional functionality enables users to filter similar reactions by their specified functional groups and candidate enzymes can be further filtered (e.g. by organisms) or expanded by Enzyme Commission number (EC) or sequence homology. Afterward, enzyme attributes (such as kcat, Km, optimal temperature and pH) can be assessed with deep learning-based methods, facilitating the swift identification of potential enzymes that can catalyze the non-natural reaction.

DeepSub: Utilizing Deep Learning for Predicting the Number of Subunits in Homo-Oligomeric Protein Complexes.

The molecular weight (MW) of an enzyme is a critical parameter in enzyme-constrained models (ecModels). It is determined by two factors: the presence of subunits and the abundance of each subunit. Although the number of subunits (NS) can potentially be obtained from UniProt, this information is not readily available for most proteins. In this study, we addressed this gap by extracting and curating subunit information from the UniProt database to establish a robust benchmark dataset. Subsequently, we propose a novel model named DeepSub, which leverages the protein language model and Bi-directional Gated Recurrent Unit (GRU), to predict NS in homo-oligomers solely based on protein sequences. DeepSub demonstrates remarkable accuracy, achieving an accuracy rate as high as 0.967, surpassing the performance of QUEEN. To validate the effectiveness of DeepSub, we performed predictions for protein homo-oligomers that have been reported in the literature but are not documented in the UniProt database. Examples include homoserine dehydrogenase from Corynebacterium glutamicum, Matrilin-4 from Mus musculus and Homo sapiens, and the Multimerins protein family from M. musculus and H. sapiens. The predicted results align closely with the reported findings in the literature, underscoring the reliability and utility of DeepSub.

Low­frequency ultrasound and microbubbles combined with simvastatin promote the apoptosis of MCF­7 cells by affecting the LATS1/YAP/RHAMM pathway.

Ultrasound scanning has widespread used in clinical practice and also has therapeutic applications. Simvastatin is a statins that is able to competitively inhibit the activity of 3­hydroxy­3­methylglutaryl­coenzyme A reductase. The aim of the present study was to investigate the roles and mechanisms of low­frequency ultrasound (LFU) and microbubbles combined with simvastatin on MCF­7 cell growth and apoptosis. Cell viability, apoptosis and cell cycle were evaluated using an MTT assay and flow cytometry, respectively. The expression of related proteins was measured by western blot assay. The results revealed that simvastatin and LFU with microbubbles reduces the viability of MCF­7 cells. The combination of LFU and microbubbles with simvastatin promoted the apoptosis of MCF­7 cells. Furthermore, it was confirmed that LFU and microbubbles combined with simvastatin affected the large tumor suppressor 1 (LATS1)/yes­associated protein (YAP)/receptor of the hyaluronan­mediated motility (RHAMM) pathway in MCF­7 cells. It was determined that LATS1 acts as a negative regulator in the LATS1/YAP/RHAMM pathway in MCF­7 cells. In conclusion, the results of the present study indicate that LFU and microbubbles combined with simvastatin promotes the apoptosis of MCF­7 cells via the LATS1/YAP/RHAMM pathway. The present study suggested a possible strategy for the treatment of breast cancer.

Early identification of hypoxic-ischemic encephalopathy by combination of magnetic resonance (MR) imaging and proton MR spectroscopy.

Brain damage following a perinatal hypoxic-ischemic encephalopathy (HIE) can be diagnosed by different techniques. The aim of the present study was to combine magnetic resonance (MR) imaging with proton MR spectroscopy in HIE diagnosis and to evaluate their correlation with outcome. A prospective observational cohort study was performed between February 2012 and February 2013. Consecutive newborns, 24 full-term neonates with HIE (mild to moderate and severe group) and 5 normal neonates, were included. Two sequential MR studies were performed; a conventional MR imaging for observation in T1 weighted image (WI) and T2WI, and proton MR spectroscopy for observation in the left or right basal ganglia and thalamus. MR images were assessed and scored by two neuroradiologists who were blinded to the clinical condition of the infants. The mild to moderate group (n=13) and severe group (n=11) were similar in the visualization of punctate hyperintensity lesions on T1WI and brain edema on T2WI. The differences of N-acetylaspartate/creatine (Cr), choline/Cr and lactate/Cr in the basal ganglia and thalamus in the HIE group were significantly different (P<0.05) compared with the control group, while no significant difference was identified between the mild to moderate and severe group (P>0.05). In conclusion, MR spectroscopy is a complementary tool for the diagnosis of HIE.

Can Dynamic Contrast-Enhanced MRI (DCE-MRI) and Diffusion-Weighted MRI (DW-MRI) Evaluate Inflammation Disease: A Preliminary Study of Crohn's Disease.

The aim of the study was to investigate diagnosis efficacy of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DW-MRI) in Crohn's disease (CD). To find out the correlations between functional MRI parameters including K, Kep, Ve, Vp, and apparent diffusion coefficient (ADC) with a serologic biomarker. The relationships between pharmacokinetic parameters and ADC were also studied.Thirty-two patients with CD (22 men, 10 women; mean age: 30.5 years) and 18 healthy volunteers without any inflammatory disease (10 men, 8 women; mean age, 34.11 years) were enrolled into this approved prospective study. Pearson analysis was used to evaluate the correlation between K, Kep, Ve, Vp, and C-reactive protein (CRP), ADC, and CRP respectively. The diagnostic efficacy of the functional MRI parameters in terms of sensitivity and specificity were analyzed by receiver operating characteristic (ROC) curve analyses. Optimal cut-off values of each functional MRI parameters for differentiation of inflammatory from normal bowel were determined according to the Youden criterion.Mean value of K in the CD group was significantly higher than that of normal control group. Similar results were observed for Kep and Ve. On the contrary, the ADC value was lower in the CD group than that in the control group. K and Ve were shown to be correlated with CRP (r = 0.725, P < 0.001; r = 0.533, P = 0.002), meanwhile ADC showed negative correlation with CRP (r = -0.630, P < 0.001). There were negative correlations between the pharmacokinetic parameters and ADC, such as K to ADC (r = -0.856, P < 0.001), and Ve to ADC (r = -0.451, P = 0.01). The area under the curve (AUC) was 0.994 for K (P < 0.001), 0.905 for ADC (P < 0.001), 0.806 for Ve (P < 0.001), and 0.764 for Kep (P = 0.002). The cut-off point of the K was found to be 0.931 min. This value provided the best trade-off between sensitivity (93.8%) and specificity (100%). The best cut-off point of ADC was 1.11 × 10 mm/s. At this level, sensitivity was 100% and specificity was 68.8%.DCE-MRI and DW-MRI were helpful in the diagnosis of CD. Quantitative MRI parameters could be used to assess the severity of inflammation. The relationships between pharmacokinetic parameters (K and Ve) and ADC reflected microstructure and microcirculation of CD to some extent.

Aggressive angiomyxoma of the pelvis: a series of four cases and literature review.

The purpose of this study was to evaluate the value of CT and MRI in aggressive angiomyxoma (AAM) of the pelvis. A series of four cases from three institutions are reviewed. Among the four cases, three were initially misdiagnosed, and local recurrence necessitated reoperation or angiographic embolization. The fourth case, with accurate preoperative diagnosis, was followed with no recurrence. CT and MR imaging demonstrated a well-defined mass, which displaced adjacent structures. Attenuation of the mass was less than that of muscle on unenhanced CT, and a swirling or layering internal architecture was found using both enhanced CT and TI-weighted MR imaging. In one patient, a layering internal architecture was seen on unenhanced CT images. MRI demonstrated the relation of the tumor to the pelvic floor better than CT. The authors concluded that both CT and MRI show the characteristic imaging pattern and trans-diaphragmatic extent of these tumors, and the diagnosis should be considered in any young woman presenting with a well-defined mass arising from the pelvis or perineum.

Diffusion tensor imaging with quantitative evaluation and fiber tractography of lumbar nerve roots in sciatica.

OBJECTIVE: To quantitatively evaluate nerve roots by measuring fractional anisotropy (FA) values in healthy volunteers and sciatica patients, visualize nerve roots by tractography, and compare the diagnostic efficacy between conventional magnetic resonance imaging (MRI) and DTI. MATERIALS AND METHODS: Seventy-five sciatica patients and thirty-six healthy volunteers underwent MR imaging using DTI. FA values for L5-S1 lumbar nerve roots were calculated at three levels from DTI images. Tractography was performed on L3-S1 nerve roots. ROC analysis was performed for FA values. RESULTS: The lumbar nerve roots were visualized and FA values were calculated in all subjects. FA values decreased in compressed nerve roots and declined from proximal to distal along the compressed nerve tracts. Mean FA values were more sensitive and specific than MR imaging for differentiating compressed nerve roots, especially in the far lateral zone at distal nerves. CONCLUSIONS: DTI can quantitatively evaluate compressed nerve roots, and DTT enables visualization of abnormal nerve tracts, providing vivid anatomic information and localization of probable nerve compression. DTI has great potential utility for evaluating lumbar nerve compression in sciatica.

Evaluation of the role of dynamic contrast-enhanced MR imaging for patients with BI-RADS 3-4 microcalcifications.

OBJECTIVE: The purpose of study was to prospectively evaluate the diagnostic performance of dynamic contrast-enhanced MR imaging in the differentiation of malignant lesions from benign ones in patients with BI-RADS 3-4 microcalcifications detected by mammography. MATERIALS AND METHODS: 93 women with 100 microcalcifications had undergone breast MRI from June 2010 to July 2013. Subsequently, 91 received open biopsy and 2 received stereotactic vacuum-assisted biopsy. All results were compared with histological findings. The PPV, NPV and area under curve (AUC) of the mammography and breast MRI were calculated. RESULTS: There were 31 (31.0%) BI-RADS 3 microcalcifications and 69 (69.0%) BI-RADS 4. The PPV and NPV of mammography is 65.2% (45/69) and 90.3% (28/31). The PPV and NPV of breast MRI was 90.2% (46/51) and 95.9% (47/49). Among 31 BI-RADS 3 microcalcifications, the PPV and NPV of breast MRI was 100% (3/3) and 100% (28/28). Among 69 BI-RADS 4 microcalcifications, the PPV and NPV of breast MRI was 89.6% (43/48) and 90.5% (19/21). The AUC of mammography and breast MRI assessment were 0.738 (95% CI, 0.639-0.837) and 0.931 (95% CI, 0.874-0.988) (p<0.05). CONCLUSION: Dynamic contrast-enhanced MR imaging of breast is able to be applied to predict the risk of malignance before follow-up for BI-RADS 3 microcalcifications and biopsy for BI-RADS 4 microcalcifications.

Necrosis degree displayed in computed tomography images correlated with hypoxia and angiogenesis in breast cancer.

OBJECTIVE: The objective of this study was to investigate the correlation between the degree of necrosis displayed in computed tomography (CT) image and the expression of hypoxic and angiogenesis biomarkers of breast cancer. METHODS: Forty-four breast cancer cases were examined with CT before surgery. Tumor specimen expressions of glucose transporter 1 (Glut1), hypoxia-inducible factor 1α (HIF-1α), carbonic anhydrase IX (CA IX), vascular endothelial growth factor (VEGF), and CD34 (as a marker of vascular endothelial cells) were detected by immunohistochemistry. RESULTS: The expressions of Glut1 and CA IX were localized primarily to the edges of necrotic areas or intraduct surface; there was a strong correlation between HIF-1α-positive expression and CA IX-positive expression (P < 0.001), and higher Glut1 or CA IX expression grade was associated with lower microvessel density (MVD) value. In CT enhanced images, lower relative CT (rCT) values were associated with more significant necrosis in the tumor; rCT value correlated positively with MVD significantly (r = 0.319, P = 0.035), and higher Glut1 or CA IX expression grade correlated with lower rCT values (P = 0.001 and 0.003, respectively). Although high VEGF expression was significantly correlated with high HIF-1α expression (P < 0.001), there were no correlations between VEGF and MVD, and HIF-1α and MVD (P = 0.559 and 0.710, respectively), and the difference of the mean rCT value between high VEGF or HIF-1α expression group and low VEGF or HIF-1α expression group was not significant. CONCLUSIONS: In breast cancer tissues, Glut1 and CA IX are key hypoxia biomarkers. Importantly, detection of necrosis in breast cancer tissue via CT enhanced imaging may prognosticate hypoxia and angiogenesis status and help to determine treatment plan of advanced breast cancer.

Value of dynamic ³¹P magnetic resonance spectroscopy technique in in vivo assessment of the skeletal muscle mitochondrial function in type 2 diabetes.

BACKGROUND: Phosphorous magnetic resonance spectroscopy ((31)P-MRS) has been successfully applied to study intracellular membrane compounds and high-energy phosphate metabolism. This study aimed to evaluate the capability of dynamic (31)P-MRS for assessing energy metabolism and mitochondrial function in skeletal muscle from type 2 diabetic patients. METHODS: Dynamic (31)P-MRS was performed on 22 patients with type 2 diabetes and 26 healthy volunteers. Spectra were acquired from quadriceps muscle while subjects were in a state of rest, at exercise and during recovery. The peak areas of inorganic phosphate (Pi), phosphocreatine (PCr), and adenosine triphosphate (ATP) were measured. The concentration of adenosine diphosphate (ADP) and the intracellular pH value were calculated from the biochemistry reaction equilibrium. The time constant and recovery rates of Pi, PCr, and ADP were analyzed using exponential curve fitting. RESULTS: As compared to healthy controls, type 2 diabetes patients had significantly lower skeletal muscle concentrations of Pi, PCr and ß-ATP, and higher levels of ADP and Pi/PCr. During exercise, diabetics experienced a significant Pi peak increase and PCr peak decrease, and once the exercise was completed both Pi and PCr peaks returned to resting levels. Quantitatively, the mean recovery rates of Pi and PCr in diabetes patients were (10.74 ± 1.26) mmol/s and (4.74 ± 2.36) mmol/s, respectively, which was significantly higher than in controls. CONCLUSIONS: Non-invasive quantitative (31)P-MRS is able to detect energy metabolism inefficiency and mitochondrial function impairment in skeletal muscle of type 2 diabetics.

Contrast material injection protocol with the flow rate adjusted to the heart rate for dual source CT coronary angiography.

To investigate the effect on coronary arterial attenuations of contrast material flow rate adjusted to a patient's heart rate during dual source CT coronary angiography (DSCT-CCTA). A total of 296 consecutive patients (mean age: 58.7 years) undergoing DSCT-CCTA without previous coronary stent placement, bypass surgery, congenital or valvular heart disease were included. The image acquisition protocol was standardized (120 kV, 380 mAs) and retrospective electrocardiograph (ECG) gating was used. Patients were randomly assigned to one of three groups [flow rate: G1: dosage/16, G2: dosage/(scan time +8), G3: fixed flow rate]. The groups were compared with respect to the attenuations of the ascending aorta (AA) above coronary ostia, the left main coronary artery (LM), the proximal right coronary artery (RCA), the left anterior descending artery (LAD), the left circumflex artery (LCX), and the contrast to noise ratio of the LM (LM(CNR)) and the proximal RCA (RCA(CNR)). Correlations between heart rate and attenuation of the coronary arteries were evaluated in three groups with linear regression. There was no significant difference in the three groups among the mean attenuations of AA (P = 0.141), LM (P = 0.068), RCA (P = 0.284), LM(CNR) (P = 0.598) and RCA(CNR) (P = 0.546). The attenuations of the LAD and the LCX in group 1 were slightly higher than those in group 2 and 3 (P < 0.05). In group 1, the attenuations of the AA (P < 0.01), LM (P < 0.01), RCA (P < 0.01), LAD (P = 0.02) and LCX (P < 0.01) decreased, respectively, with an increasing heart rate. A similar finding was detected in group 3 (AA: P < 0.01, LM: P < 0.01, RCA: P < 0.01, LAD: P < 0.01 and LCX: P < 0.01). In contrast, the attenuations of the AA (P = 0.55), LM (P = 0.27), RCA (P = 0.77), LAD (P = 0.22) and LCX (P = 0.74) had no significant correlation with heart rate in group 2. In all three groups, LM(CNR) (P = 0.77, 0.69 and 0.73 respectively) and RCA(CNR) (P = 0.75, 0.39 and 0.61 respectively) had no significant correlation with heart rate. Contrast material flow rate adjusted to heart rate can diminish the influence of heart rate on attenuations of the coronary arteries in DSCT-CCTA.

Factors influencing delay time and coronary arterial density during coronary angiography with DSCT.

BACKGROUND: CT angiography (CTA) plays an important role in diagnosing coronary arterial disease. Delay time and density of the coronary arteries related with patient-specific factors are essential for getting an optimal CTA image. PURPOSE: To investigate various factors influencing delay time and coronary arterial density during coronary CTA with dual source CT. MATERIAL AND METHODS: One hundred and sixteen consecutive subjects who underwent cardiac DSCT with retrospective ECG-gating were included. Factors including gender, age, height, weight, transversal cardiac diameter (TCD), transversal thoracic diameter (TTD), heart rate (HR), body surface area (BSA = [weight × height/3600](1/2)) and cardiothoracic ratio (CTR = TCD/TTD) were recorded, measured and calculated before administration of contrast media during coronary CT angiography. Delay time was determined as duration from the beginning of the injection to the density in the descending aorta at the level of right main pulmonary artery reaching a threshold of 100 HU. Coronary arterial density was measured at the mid portion of the right coronary artery. Regression analysis and stepwise regression analysis were used to investigate the influence of these factors on delay time and coronary arterial density. RESULTS: Delay time decreased with an increasing HR and it was shorter in women than men. Delay time increased with an increasing TCD. Delay time could be predicted by the formula: DT = 16.651-0.110 × HR + 1.902 × gender + 0.394 × TCD (where DT is abbreviation for delay time, gender is 0 for women and 1 for men). Coronary arterial density decreased with an increasing HR and weight. Coronary arterial density could be predicted by the formula: CAD = 923.42-4.099 × HR-3.293 × weight (CAD = coronary arterial density). There was no relationship between the other factors mentioned above and delay time or coronary arterial density. CONCLUSION: Delay time is influenced by HR, gender and TCD. Coronary arterial density also changes with HR and weight. So HR, gender, TCD and weight can be used to adjust flow rate and dosage of contrast media before administration of contrast media during coronary CT angiography.

Evaluation of computed tomography obstruction index in guiding therapeutic decisions and monitoring percutanous catheter fragmentation in massive pulmonary embolism.

In the present study, we evaluated computed tomography pulmonary angiography (CTPA) in guiding therapeutic decisions and monitoring patients undergoing percutaneous catheter fragmentation in acute massive pulmonary embolism. From Jan 2003 to Dec 2009, 35 patients were diagnosed with acute massive pulmonary embolism by CTPA (T0) and treated with percutaneous catheter fragmentation. The severity was assessed by CT obstruction index (Qanadli index) and compared with Miller index. CTPA, oxygen saturation (SaO2) and pulmonary artery pressure were performed as follow-up index. The mean percentage of Qanadli index was (55±13)% (range, 40%-75%), and Miller index was (62±15)% (range, 45%-85%). Correlations between them were statistically significant (r = 0.867, P < 0.0001). The Qanadli index showed significant reduction [T0: (55±13)%; T1: (12±10)%; P < 0.001] in 33 patients. Significant correlation was observed between the Qanadli index, SaO2 (r = 0.934), and pulmonary artery pressure (r = 0.813). The Qanadli index provides an accurate method for distinguishing massive pulmonary embolism from sub-massive pulmonary embolism. It can be used to determine therapeutic options and monitor clinical outcomes.

Comparison of dual-source CT coronary angiography and conventional coronary angiography for detecting coronary artery disease.

To evaluate the diagnostic accuracy of dual-source CT coronary angiography for detecting coronary artery stenosis. From February 2008 to January 2009, dual-source CT coronary CT angiography (DSCT-CCTA) and conventional coronary angiography (CAG) were both performed in 84 patients who had either clinical symptoms or a high risk of coronary artery disease. The diagnostic accuracy of DSCT-CCTA was evaluated by comparing it with that of CAG, which was regarded as the gold standard for making the diagnosis of coronary artery disease. Occlusion or stenosis of various degrees was revealed by DSCT-CCTA in 244 segments of 84 patients. Compared to CAG, segment-based sensitivity, specificity, positive predictive value and negative predictive value of DSCT-CCTA were 97.4, 97.8, 92.2 and 100%, respectively. The diagnostic accuracy of DSCT-CCTA for the detection of coronary artery stenosis was 96.5%. The paired chi2 tests revealed no significant difference between DSCT-CCTA and CAG for making the diagnosis of coronary artery disease (P = 0.076). The diagnostic performance of DSCT-CCTA is generally as accurate as that of CAG. Thus, DSCT-CCTA is a reliable non-invasive method for detecting coronary artery stenosis.

Review of CT angiography of aorta.

The most common imaging modality used for diagnosis of aortic disease is CT, followed by transesophageal echocardiography, MRI, and aortography. If multiple imaging is performed, the initial imaging technique most frequently employed is computerized tomography. During the past decade, computed tomographic angiography (CTA) has become a standard non-invasive imaging modality for the depiction of vascular anatomy and pathology. The quality and speed of CTA examinations have increased dramatically as CT technology has evolved from-channel spiral CT systems to multichannel (4-, 8-, 10- and 16-slice) spiral CT system. The quality and speed of CTA is superior to other imaging modalities, and it is also cheaper and less invasive. CTA of the aorta has proven to be superior in diagnostic accuracy to conventional arteriography in several applications.