BAF-Net: bidirectional attention-aware fluid pyramid feature integrated multimodal fusion network for diagnosis and prognosis.

Objective. To go beyond the deficiencies of the three conventional multimodal fusion strategies (i.e. input-, feature- and output-level fusion), we propose a bidirectional attention-aware fluid pyramid feature integrated fusion network (BAF-Net) with cross-modal interactions for multimodal medical image diagnosis and prognosis.Approach. BAF-Net is composed of two identical branches to preserve the unimodal features and one bidirectional attention-aware distillation stream to progressively assimilate cross-modal complements and to learn supplementary features in both bottom-up and top-down processes. Fluid pyramid connections were adopted to integrate the hierarchical features at different levels of the network, and channel-wise attention modules were exploited to mitigate cross-modal cross-level incompatibility. Furthermore, depth-wise separable convolution was introduced to fuse the cross-modal cross-level features to alleviate the increase in parameters to a great extent. The generalization abilities of BAF-Net were evaluated in terms of two clinical tasks: (1) an in-house PET-CT dataset with 174 patients for differentiation between lung cancer and pulmonary tuberculosis. (2) A public multicenter PET-CT head and neck cancer dataset with 800 patients from nine centers for overall survival prediction.Main results. On the LC-PTB dataset, improved performance was found in BAF-Net (AUC = 0.7342) compared with input-level fusion model (AUC = 0.6825;p< 0.05), feature-level fusion model (AUC = 0.6968;p= 0.0547), output-level fusion model (AUC = 0.7011;p< 0.05). On the H&N cancer dataset, BAF-Net (C-index = 0.7241) outperformed the input-, feature-, and output-level fusion model, with 2.95%, 3.77%, and 1.52% increments of C-index (p= 0.3336, 0.0479 and 0.2911, respectively). The ablation experiments demonstrated the effectiveness of all the designed modules regarding all the evaluated metrics in both datasets.Significance. Extensive experiments on two datasets demonstrated better performance and robustness of BAF-Net than three conventional fusion strategies and PET or CT unimodal network in terms of diagnosis and prognosis.

Optimal batch determination for improved harmonization and prognostication of multi-center PET/CT radiomics feature in head and neck cancer.

Objective. To determine the optimal approach for identifying and mitigating batch effects in PET/CT radiomics features, and further improve the prognosis of patients with head and neck cancer (HNC), this study investigated the performance of three batch harmonization methods.Approach. Unsupervised harmonization identified the batch labels by K-means clustering. Supervised harmonization regarding the image acquisition factors (center, manufacturer, scanner, filter kernel) as known/given batch labels, and Combat harmonization was then implemented separately and sequentially based on the batch labels, i.e. harmonizing features among batches determined by each factor individually or harmonizing features among batches determined by multiple factors successively. Extensive experiments were conducted to predict overall survival (OS) on public PET/CT datasets that contain 800 patients from 9 centers.Main results. In the external validation cohort, results show that compared to original models without harmonization, Combat harmonization would be beneficial in OS prediction with C-index of 0.687-0.740 versus 0.684-0.767. Supervised harmonization slightly outperformed unsupervised harmonization in all models (C-index: 0.692-0.767 versus 0.684-0.750). Separate harmonization outperformed sequential harmonization in CT_m+clinic and CT_cm+clinic models with C-index of 0.752 and 0.722, respectively, while sequential harmonization involved clinical features in PET_rs+clinic model further improving the performance and achieving the highest C-index of 0.767.Significance. Optimal batch determination especially sequential harmonization for Combat holds the potential to improve the prognostic power of radiomics model in multi-center HNC dataset with PET/CT imaging.

Functional-structural sub-region graph convolutional network (FSGCN): Application to the prognosis of head and neck cancer with PET/CT imaging.

BACKGROUND AND OBJECTIVE: Accurate risk stratification is crucial for enabling personalized treatment for head and neck cancer (HNC). Current PET/CT image-based prognostic methods include radiomics analysis and convolutional neural network (CNN), while extracting radiomics or deep features in grid Euclidean space has inherent limitations for risk stratification. Here, we propose a functional-structural sub-region graph convolutional network (FSGCN) for accurate risk stratification of HNC. METHODS: This study collected 642 patients from 8 different centers in The Cancer Imaging Archive (TCIA), 507 patients from 5 centers were used for training, and 135 patients from 3 centers were used for testing. The tumor was first clustered into multiple sub-regions by using PET and CT voxel information, and radiomics features were extracted from each sub-region to characterize its functional and structural information, a graph was then constructed to format the relationship/difference among different sub-regions in non-Euclidean space for each patient, followed by a residual gated graph convolutional network, the prognostic score was finally generated to predict the progression-free survival (PFS). RESULTS: In the testing cohort, compared with radiomics or FSGCN or clinical model alone, the model PETCTFea_CTROI + Cli that integrates FSGCN prognostic score and clinical parameter achieved the highest C-index and AUC of 0.767 (95% CI: 0.759-0.774) and 0.781 (95% CI: 0.774-0.788), respectively for PFS prediction. Besides, it also showed good prognostic performance on the secondary endpoints OS, RFS, and MFS in the testing cohort, with C-index of 0.786 (95% CI: 0.778-0.795), 0.775 (95% CI: 0.767-0.782) and 0.781 (95% CI: 0.772-0.789), respectively. CONCLUSIONS: The proposed FSGCN can better capture the metabolic or anatomic difference/interaction among sub-regions of the whole tumor imaged with PET/CT. Extensive multi-center experiments demonstrated its capability and generalization of prognosis prediction in HNC over conventional radiomics analysis.

An automatic segmentation method with self-attention mechanism on left ventricle in gated PET/CT myocardial perfusion imaging.

OBJECTIVES: We aimed to propose an automatic segmentation method for left ventricular (LV) from 16 electrocardiogram (ECG) -gated 13N-NH3 PET/CT myocardial perfusion imaging (MPI) to improve the performance of LV function assessment. METHODS: Ninety-six cases with confirmed or suspected obstructive coronary artery disease (CAD) were enrolled in this research. The LV myocardial contours were delineated by physicians as ground truth. We developed an automatic segmentation method, which introduces the self-attention mechanism into 3D U-Net to capture global information of images so as to achieve fine segmentation of LV. Three cross-validation tests were performed on each gate (64 vs. 32 for training vs. validation). The effectiveness was validated by quantitative metrics (modified hausdorff distance, MHD; dice ratio, DR; 3D MHD) as well as cardiac functional parameters (end-systolic volume, ESV; end-diastolic volume, EDV; ejection fraction, EF). Furthermore, the feasibility of the proposed method was also evaluated by intra- and inter-observers with DR and 3D-MHD. RESULTS: Compared with backbone network, the proposed approach improved the average DR from 0.905 ± 0.0193 to 0.9202 ± 0.0164, and decreased the average 3D MHD from 0.4611 ± 0.0349 to 0.4304 ± 0.0339. The average relative error of LV volume between proposed method and ground truth is 1.09±3.66%, and the correlation coefficient is 0.992 ± 0.007 (P < 0.001). The EDV, ESV, EF deduced from the proposed approach were highly correlated with ground truth (r ≥ 0.864, P < 0.001), and the correlation with commercial software is fair (r ≥ 0.871, P < 0.001). DR and 3D MHD of contours and myocardium from two observers are higher than 0.899 and less than 0.5194. CONCLUSION: The proposed approach is highly feasible for automatic segmentation of the LV cavity and myocardium, with potential to benefit the precision of LV function assessment.

O-Glycosylating Enzyme GALNT2 Predicts Worse Prognosis in Cervical Cancer.

Identification of novel biomarkers is helpful for the diagnosis and treatment of cervical cancer. Mucin glycosylating enzyme GALNT2 modulates mucin O-glycosylation, and has been revealed as a regulator of tumorigenesis in various cancers. However, the expression pattern of GALNT2 in cervical cancer is still unclear. In this study, we demonstrated that the mRNA expression and protein level of GALNT2 were increased in cervical high-grade intraepithelial neoplasia and tumor tissues compared with normal cervix tissues. Kaplan-Meier plotter showed that overexpression of GALNT2 was associated with worse overall survival in TCGA cohort (p < 0.001, HR = 2.65, 95% CI = 1.62-4.34) and poor disease free survival in GSE44001 cohort (p = 0.0218, HR = 2.15, 95% CI = 1.14-4.06). In addition, GSEA analysis showed that various immune-related pathways were closely related to the expression of GALNT2 in cervical cancer. Moreover, co-expression of GALNT2 and IL1A, IL1B, IL11, CXCL1, CXCL2, CXCL5, CXCL6, CXCR1, or CCR3 predicted poor overall survival, and the expression of GALNT2 also affected the prognostic value of CD47, CD274, CD276, CSF1R, TNFSF9, and TNFSF11 in cervical cancer patients. These findings suggest that GALNT2 might be used as a prognostic biomarker in cervical cancer.

Panic disorder aging characteristics: The role of telomerase reverse transcriptase gene and brain function.

Panic disorder (PD) causes serious functional damage and disability and accelerates the process of individual aging. The pathological basis of PD is the same as that of age-related diseases, which is proposed as a new viewpoint in recent years. Memory decline and social functional impairment are common manifestations of accelerated aging in PD. The function of telomerase reverse transcriptase (TERT) and telomere length (TL) is abnormal in patients with aging and PD. However, the molecular mechanism behind remains unclear. The purpose of this study was to explore the relationship between TERT gene expression (including DNA methylation) and the changes in PD aging characteristics (memory and social function). By TERT gene knockout mice, we found that loss of TERT attenuated the acquisition of recent fear memory during contextual fear conditioning. This study reported that a significantly lower methylation level of human TERT (hTERT) gene was detected in PD patients compared with healthy control and particularly decreased CpG methylation in the promoter region of hTERT was associated with the clinical characteristics in PD. Regional homogeneity (ReHo) analysis showed that the methylation of hTERT (cg1295648) influenced social function of PD patients through moderating the function of the left postcentral gyrus (PCG). This indicates that the hTERT gene may play an important role in the pathological basis of PD aging and may become a biological marker for evaluating PD aging. These findings provide multidimensional evidence for the underlying genetic and pathological mechanisms of PD.

Rhizomucor pusillus Infection in a Patient with Acute Myeloid Leukaemia After Haematopoietic Stem Cell Transplantation: Clinical Impact of Metagenomics Next-Generation Sequencing.

Long-term chemotherapy and immunosuppressants in acute myeloid leukaemia (AML) patients can result in a high risk of opportunistic infections. Rhizomucor pusillus is an opportunistic pathogen that exists in nature, but infection caused by R. pusillus is rare in the clinic. Notably, the sensitivity and detection time of conventional diagnostic tools for this fungus usually falls short of the needs of clinical diagnosis, resulting in treatment failure. Currently, metagenomics next-generation sequencing (mNGS) has played an important role in the detection of pathogens. Here, we report a case of R. pusillus pneumonia in a haematopoietic stem cell transplantation (HSCT) patient, detected by the mNGS method.

Glutamic Acid Decarboxylase 1 Gene Methylation and Panic Disorder Severity: Making the Connection by Brain Gray Matter Volume.

Objective: This study aimed to test the hypothesis that the relationship between glutamic acid decarboxylase (GAD) 1 gene methylation and severity of clinical symptoms of panic disorder (PD) is mediated by the effect of GAD1 gene methylation on gray matter volume (GMV) and the effect of GMV on PD. Methods: Panic disorder (n = 24) patients were recruited consecutively from the Affiliated Brain Hospital of Nanjing Medical University through outpatient and public advertising, eligible healthy controls (HCs) (n = 22) were recruited from public advertising. We compared GMV and GAD1 gene methylation in PD and HCs to estimate the differences, and on the basis of the relationship between gray matter volumes and GAD1 gene methylation in PD patients was evaluated, the role of GMV as a mediator of GAD1 gene methylation and PD clinical symptoms was analyzed. Results: Panic disorder patients had significantly lower methylation in the GAD1 promoter region on Cytosine-phosphate-guanine (CPG) 7 than HCs (t = 2.380, p = 0.021). Pearson correlation analysis found a significant negative association between cg171674146 (cg12) site and clinical severity (n = 24, r = -0.456, p = 0.025). Compared to HCs, patients with PD had decreased gray matter volumes in several brain regions, which were also associated with PD severity. Left postcentral gyrus (PoCG) GMV mediated the association between cg12 methylation and PD severity, and there was a significant mediation effect of right angular gyrus (ANG) gray matter volumes on the relationship between cg12 methylation and PD severity. Limitation: No direct results can be derived for methylation patterns in different brain regions; the study is cross-sectional; relatively small size.

Neural Effects of Cognitive Behavioral Therapy in Psychiatric Disorders: A Systematic Review and Activation Likelihood Estimation Meta-Analysis.

Background: Cognitive behavioral therapy (CBT) is a first-line psychotherapeutic treatment that has been recommended for psychiatric disorders. Prior neuroimaging studies have provided preliminary evidence suggesting that CBT can have an impact on the activity of brain regions and functional integration between regions. However, the results are far from conclusive. The present article aimed to detect characteristic changes in brain activation following CBT across psychiatric disorders. Method: Web of Science, Cochrane Library, Scopus, and PubMed databases were searched to identify whole-brain functional neuroimaging studies of CBT through 4 August 2021. To be included in the meta-analysis, studies were required to examine functional activation changes between pre-and post-CBT. The included studies were then divided into subgroups according to different task paradigms. Then, an activation likelihood estimation algorithm (ALE) was performed in the different meta-analyses to identify whether brain regions showed consistent effects. Finally, brain regions identified from the meta-analysis were categorized into eight functional networks according to the spatial correlation values between independent components and the template. Results: In total, 13 studies met inclusion criteria. Three different meta-analyses were performed separately for total tasks, emotion tasks, and cognition tasks. In the total task ALE meta-analysis, the left precuneus was found to have decreased activation. For the cognition task ALE meta-analysis, left anterior cingulate (ACC) and left middle frontal gyrus (MFG) were found to have decreased activation following CBT. However, the emotion task ALE meta-analysis did not find any specific brain regions showing consistent effects. A review of included studies revealed default mode network (DMN), executive control network (ECN), and salience network (SN) were the most relevant among the eight functional networks. Conclusion: The results revealed that the altered activation in the prefrontal cortex and precuneus were key regions related to the effects of CBT. Therefore, CBT may modulate the neural circuitry of emotion regulation. This finding provides recommendations for the rapidly developing literature.

A meta-analysis on neural changes of cognitive training for mental disorders in executive function tasks: increase or decrease brain activation?

BACKGROUND: Cognitive impairment is often found in patients with psychiatric disorders, and cognitive training (CT) has been shown to help these patients. To better understand the mechanisms of CT, many neuroimaging studies have investigated the neural changes associated with it. However, the results of those studies have been inconsistent, making it difficult to draw conclusions from the literature. Therefore, the objective of this meta-analysis was to identify consistent patterns in the literature of neural changes associated with CT for psychiatric disorders. METHODS: We searched for cognitive training imaging studies in PubMed, Cochrane library, Scopus, and ProQuest electronic databases. We conducted an activation likelihood estimation (ALE) for coordinate-based meta-analysis of neuroimaging studies, conduct behavioral analysis of brain regions identified by ALE analysis, conduct behavioral analysis of brain regions identified by ALE analysis, and then created a functional meta-analytic connectivity model (fMACM) of the resulting regions. RESULTS: Results showed that CT studies consistently reported increased activation in the left inferior frontal gyrus (IFG) and decreased activation in the left precuneus and cuneus from pre- to post- CT. CONCLUSION: CT improves cognitive function by supporting language and memory function, and reducing neuronal resources associated with basic visual processing.

Altered spontaneous neural activity in frontal and visual regions in patients with acrophobia.

BACKGROUND: Acrophobia is a prevalent type of specific phobia, which frequently leads to functional impairments and occupational limitations. However, the neural pathology of acrophobia is still largely unknown. METHODS: 26 acrophobic patients and 30 healthy controls were enrolled in this study. All participants underwent a resting-state fMRI scan. Severity of symptoms was evaluated using self-report and behavioral measures. The regional homogeneity (ReHo) and seed-based functional connectivity (FC) were then examined. RESULTS: Compared to controls, acrophobic patients demonstrated higher ReHo in the right fusiform gyrus and lower ReHo in the bilateral superior frontal gyrus. Lower FC of right fusiform gyrus-bilateral caudate, right fusiform gyrus-right parahippocampal gyrus, and left medial superior frontal gyrus-left cuneus was also found in the acrophobia group. Additionally, there were negative correlations between behavior avoidance scores and FC of right fusiform gyrus- right parahippocampal gyrus (r = -0.42, p = 0.04) and between scores of the 7-item generalized anxiety disorder scale and FC of left medial superior frontal gyrus- left cuneus (r = -0.40, p = 0.049) in the acrophobia group. LIMITATIONS: Owing to the cross-sectional design, it was unclear whether the functional abnormalities found in the acrophobic patients were related to state or trait effects. CONCLUSIONS: Preliminary results indicated that acrophobic patients revealed abnormal brain function in orbitofrontal cortex, medial prefrontal cortex, and visual regions. These abnormalities may be helpful in understanding the possible neurobiological mechanism of acrophobia and may serve as potential intervention and prevention targets.

Failure Criteria and Constitutive Relationship of Lightweight Aggregate Concrete under Triaxial Compression.

This paper investigates the compression behavior and failure criteria of lightweight aggregate concrete (LAC) under triaxial loading. A total of 156 specimens were tested for three parameters: concrete strength, lateral confining pressure and aggregate immersion time, and their effects on the failure mode of LAC and the triaxial stress-strain relationship of LAC is studied. The research indicated that, as the lateral constraint of the specimen increases, the failure patterns change from vertical splitting failure to oblique shearing failure and then to indistinct traces of damage. The stress-strain curve of LAC specimens has an obvious stress plateau, and the curve no longer appears downward when the confining pressure exceeds 12 MPa. According to the experimental phenomenon and test data, the failure criterion was examined on the Mohr-Coulomb theory, octahedral shear stress theory and Rendulic plane stress theory, which well reflects the behavior of LAC under triaxial compression. For the convenience of analysis and application, the stress-strain constitutive models of LAC under triaxial compression are recommended, and these models correlate well with the test results.

Chemical profiling and quality evaluation of Pogostemon cablin Benth by liquid chromatography tandem mass spectrometry combined with multivariate statistical analysis.

Pogostemon cablin Benth (PCB) is a well-known traditional Chinese medicine that has been used for treatment of many ailments for several centuries. In presently, the chemical profiling and quality control study of PCB has mainly concentrated on the volatile fractions. However, the non-volatile chemical profile of PCB was still unclear. In this study, 73 non-volatile constituents (i.e., 33 flavonoids, 21 organic acids, 9 phenylpropanoids, 4 sesquiterpenes, 3 alkaloids, and 3 other types of compounds) were identified and characterized in PCB using high performance liquid chromatography coupled with quadruple time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS). Meanwhile, to assess PCB samples, an established HPLC-Q-TOF-MS fingerprint was combined with multivariate statistical analysis that included similarity analysis (SA), hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA). The PCB samples could be classified into two groups (herbal decoction pieces and processed medicinal materials), and acteoside, isoacteoside, 4',6-Dihydroxy-5,7-dimethoxyflavone, pachypodol and pogostone were screened as the potential chemical markers that attributed classification. In addition, nine representative components (pachypodol, vicenin-2, apigenin, rhamnocitrin, acteoside, isoacteoside, chlorogenic acid, azelaic acid and pogostone) in PCB were simultaneously determined by using an ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QQQ-MS/MS). This study is the first to describe the chemical profile of PCB using liquid chromatography tandem mass spectrometry, which would improve our understanding of the substance basis of PCB and is helpful to the PCB further quality evaluation.

The Life Cycle and Ultrastructure of the Host Response of the Smut Pathogen Anthracocystis destruens on Broomcorn Millet.

Broomcorn millet smut caused by the fungus Anthracocystis destruens is one of the most destructive diseases in broomcorn millet production. The life cycle of A. destruens and host defense responses against A. destruens remain elusive. Here we investigated the disease symptom development and the parasitic process of A. destruens as well as the ultrastructure of the host-pathogen interface. The results showed that there are four typical symptoms of broomcorn millet smut, which are blackfly, cluster leaves, hedgehog head, and incomplete fruiting. A. destruens colonizes all tissues of broomcorn millet but produces teliospores only in the inflorescence. After infection, A. destruens proliferates in the host, likely in a systemic manner. Ultrastructural study of the infected inflorescence showed that the pathogen grows intercellularly and intracellularly within the host. The host activates defense response to prevent pathogen infection, accumulation of callose analogs and highly electron-dense deposits to resist A. destruens infection.

Efficacy of mite allergen immunotherapy in allergic rhinitis and the immune synergistic effect on cross-allergens.

Aim: To compare the efficacy of single- and double-species mite allergen immunotherapy. Materials and methods: An open, pseudo-randomized, controlled study was conducted (n = 125 allergic rhinitis patients). The primary end point involved the visual analogue scale. Secondary end points included a basophil activation test and serum specific IgE and IgG4 assays. Results: Visual analogue scale analysis indicated considerable reductions in both groups. Both treatments improved quality of life and induced sIgG4 antibody production. Basophil activation and serum IgE inhibition were not evident in either treatment. Neither treatment displayed an early stage immune synergistic effect on cross-allergens. Conclusions: Both treatments were effective against allergic rhinitis, and statistical differences were not observed. Future studies may require long-term, large-scale research.

Lay abstract This study is relevant because the worldwide prevalence of allergic rhinitis (AR) is increasing. Although previous studies have confirmed the efficacy of subcutaneous immunotherapy comprising a single allergen over that comprising a mixed allergen for AR treatment, the clinical efficacy of these allergen immunotherapies (AITs) has not been compared via a well-designed study. Thus, the findings of this study could considerably contribute to the knowledge in this area. The current study compared the efficacy of single-mite AIT (SM-AIT) with that of double-mite AIT (DM-AIT) in AR. Both standardized SM-AIT and DM-AIT improved quality of life. Both standardized SM-AIT and DM-AIT were effective against AR.

Dynamic PET image reconstruction incorporating a median nonlocal means kernel method.

In dynamic positron emission tomography (PET) imaging, the reconstructed image of a single frame often exhibits high noise due to limited counting statistics of projection data. This study proposed a median nonlocal means (MNLM)-based kernel method for dynamic PET image reconstruction. The kernel matrix is derived from median nonlocal means of pre-reconstructed composite images. Then the PET image intensities in all voxels were modeled as a kernel matrix multiplied by coefficients and incorporated into the forward model of PET projection data. Then, the coefficients of each feature were estimated by the maximum likelihood method. Using simulated low-count dynamic data of Zubal head phantom, the quantitative performance of the proposed MNLM kernel method was investigated and compared with the maximum-likelihood method, conventional kernel method with and without median filter, and nonlocal means (NLM) kernel method. Simulation results showed that the MNLM kernel method achieved visual and quantitative accuracy improvements (in terms of the ensemble mean squared error, bias versus variance, and contrast versus noise performances). Especially for frame 2 with the lowest count level of a single frame, the MNLM kernel method achieves lower ensemble mean squared error (10.43%) than the NLM kernel method (13.68%), conventional kernel method with and without median filter (11.88% and 23.50%), and MLEM algorithm (24.77%). The study on real low-dose 18F-FDG rat data also showed that the MNLM kernel method outperformed other methods in visual and quantitative accuracy improvements (in terms of regional noise versus intensity mean performance).

Pharmacokinetics, plasma protein binding, and metabolism of a potential natural chemosensitizer from Marsdenia tenacissima in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima (Roxb.) Wight et Arn is a medicinal plant mainly distributed in southwest China. It is used in folk medicine for the treatment of tumors and is synergistic with chemotherapies. In our previous study, 11α-O-2-methybutyryl-12ß-O-tigloyl-tenacigenin B (MT2), a main steroid aglycone isolated from the total aglycones of M. tenacissima, significantly enhanced the in vivo antitumor effect of paclitaxel in mice bearing human tumor xenografts, showing its potential as a chemosensitizer. However, the pharmacokinetic characteristics, plasma protein binding rate, and metabolic profile of MT2 remain unclear. AIM OF THE STUDY: To elucidate the pharmacokinetic characteristics, plasma protein binding rate, and metabolic profile of MT2 in rats. MATERIALS AND METHODS: MT2 in rat plasma and phosphate-buffered saline was quantified using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method, while the MT2 metabolites in rat liver microsomes were analyzed using UPLC-triple time-of-flight MS/MS. RESULTS: For intravenously administered MT2, the maximum plasma concentration and the area under the plasma concentration-time curve indicated dose dependency, while the elimination half-life time, the mean residence time, apparent volume of distribution and total apparent clearance values remained relatively unchanged in both the 5 mg/kg and 10 mg/kg groups. For orally administered MT2, the bioavailability was 1.08-1.11%. In rat plasma, MT2 exhibited a protein binding rate of 93.84-94.96%. In rat liver microsomes, MT2 was metabolized by oxidation alone or in combination with demethylation, and five MT2 metabolites were identified. CONCLUSION: MT2 has low oral bioavailability and a high plasma protein binding rate in rats. After administration, MT2 is transformed into oxidative metabolites in the liver. To achieve a high blood concentration of MT2, it should be administered intravenously. These findings would serve as a reference for further MT2-based pharmacological study and drug development.

Study on the Strength Performance of Recycled Aggregate Concrete with Different Ages under Direct Shearing.

In order to study the mechanical properties of recycled aggregate concrete (RAC) at different ages, 264 standard cubes were designed to test its direct shear strength and cube compressive strength while considering the parameters of age and recycled aggregate replacement ratio. The failure pattern and load-displacement curve of specimens at direct shearing were obtained; the direct shear strength and residual shear strength were extracted from the load-displacement curves. Experimental results indicate that the influence of the replacement ratio for the front and side cracks of RAC is insignificant, with the former being straight and the latter relatively convoluted. At the age of three days, the damaged interface between aggregate and mortar is almost completely responsible for concrete failure; in addition to the damage of coarse aggregates, aggregate failure is also an important factor in concrete failure at other ages. The load-displacement curve of RAC at direct shearing can be divided into elasticity, elastoplasticity, plasticity, and stabilization stages. The brittleness of concrete decreases with its age, which is reflected in the gradual shortening of the elastoplastic stage. At 28 days of age, the peak direct shear force increases with the replacement ratio, while the trend is opposite at ages of 3 days, 7 days, and 14 days, respectively. The residual strength of RAC decreases inversely to the replacement ratio, with the rate of decline growing over time. A two-parameter RAC direct shear strength calculation formula was established based on the analysis of age and replacement rate to peak shear force of RAC. The relationship between cube compressive strength and direct shear strength of recycled concrete at various ages was investigated.

Pharmacokinetic studies of six major 2-(2-phenylethyl) chromones in rat plasma using ultra high performance liquid chromatography with tandem mass spectrometry after oral administration of agarwood ethanol extract.

In this study, a simple, quick, sensitive and reliable method utilizing ultra-high performance liquid chromatography with tandem mass spectrometry method was validated for simultaneous quantification of six main 2-(2-phenylethyl) chromones, including agarotetrol, isoagarotetrol, (5S,6R,7R,8S)-5,6,7,8-tetrahydroxy-(4-methoxyphenethyl)-5,6,7,8-tetrahydro-4H-chromen-4-one, 8-chloro-2-(2-phenyl ethyl)-5,6,7-trihydroxy-5,6,7,8-tetrahydrochromone, 6,7-dimethoxy-2-(2-phenylethyl) chromone, and 2-(2-phenylethyl) chromone in rat plasma after oral administration of agarwood ethanol extract. Separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm) using gradient elution with mobile phase of 0.2% formic acid-water and acetonitrile. The tandem mass was performed in the multiple reaction monitoring mode with positive ionization. The calibration curves indicated good linearity (r2  > 0.99) over the corresponding concentration range. The precision and accuracy were within the acceptable range. Mean absolute recoveries of all analytes were between 73.31% and 94.76%, and the relative standard deviations of matrix effects were not higher than 15%. The six analytes were proven to be stable during sample storage and analysis procedures. The validated method was successfully applied to pharmacokinetic study of six 2-(2-phenylethyl) chromones in rat after oral administration of agarwood ethanol extract for the first time. This study could serve as a reference and provide theoretical guidance for further pharmacodynamic research and clinical applications of agarwood.

Isolation and Characterization of Phosphorus Solubilizing Bacteria With Multiple Phosphorus Sources Utilizing Capability and Their Potential for Lead Immobilization in Soil.

Phosphorus solubilizing bacteria (PSB) can promote the level of plant-absorbable phosphorus (P) in agro-ecosystems. However, little attention has been paid to PSB harboring abilities in utilizing multiple phosphorus sources and their potentials for heavy metal immobilization. In this study, we applied the strategy of stepwise acclimation by using Ca3(PO4)2, phytate, FePO4, and AlPO4 as sole P source. We gained 18 PSB possessing abilities of multiple P sources utilization, and these bacteria belonged to eight genera (Acinetobacter, Pseudomonas, Massilia, Bacillus, Arthrobacter, Stenotrophomonas, Ochrobactrum, and Cupriavidus), and clustered to two apparent parts: Gram-positive bacteria and Gram-negative bacteria. The isolate of Acinetobacter pittii gp-1 presented good performance for utilizing Ca3(PO4)2, FePO4, AlPO4, and phytate, with corresponding P solubilizing levels were 250.77, 46.10, 81.99, and 7.91 mg/L PO4 3--P, respectively. The PSB A. pittii gp-1 exhibited good performance for solubilizing tricalcium phosphate in soil incubation experiments, with the highest values of water soluble P and available P were 0.80 and 1.64 mg/L, respectively. Additionally, the addition of A. pittii gp-1 could promote the immobilization of lead (Pb), and the highest Pb immobilization efficiency reached 23%. Simultaneously, we found the increases in abundances of both alkaline phosphatase gene (phoD) and ß-propeller phytase gene (bpp) in strain gp-1 added soils. Besides, we observed the expression up-regulation of both pyrroloquinoline quinone gene (pqq) and polyphosphate kinases gene (ppk), with the highest relative expression levels of 18.18 and 5.23, respectively. We also found the polyphosphate particles using granule staining. To our knowledge, our findings first suggest that the solubilizing of tricalcium phosphate by phosphorus solubilizing bacterium belonging to Acinetobacter is coupled with the synthesis of polyphosphate. Taken together, A. pittii gp-1 could be a good candidate in improving soil fertility and quality.