Adaptive phase retrieval algorithm for local highlight area based on a piecewise sine function.

Phase measuring profilometry (PMP) has been widely used in industries for three-dimensional (3D) shape measurement. However, phase information is often lost due to image saturation results from high-reflection object surfaces, leading to subsequent 3D reconstruction errors. To address the problem, we propose an adaptive phase retrieval algorithm that can accurately fit the sinusoidal fringes damaged by high reflection in the saturated regions to retrieve the lost phase information. Under the proposal, saturated regions are first identified through a minimum error thresholding technique to narrow down regions of interest and so that computation costs are reduced. Then, images with differing exposures are fused to locate peak-valley coordinates of the fitting sinusoidal fringes. And the corresponding values of peak-valley pixels are obtained based on a least squares method. Finally, an adaptive piecewise sine function is constructed to recover the sinusoidal fringe pattern by fitting the pattern intensity distribution. And the existing PMP technology is used to obtain phase information from the retrieved sinusoidal fringes. To apply the developed method, only one (or two) image with different exposure times is needed. Compared with existing methods for measuring reflective objects, the proposed method has the advantages of short operation time, reduced system complexity, and low demand on hardware equipment. The effectiveness of the proposed method is verified through two experiments. The developed methodology provides industry an alternative way to measure high-reflection objects in a wide range of applications.

Haploidentical transplant for paediatric patients with severe thalassaemia using post-transplant cyclophosphamide and methotrexate: A prospectively registered multicentre trial from the Bone Marrow Failure Working Group of Hunan Province, China.

Haploidentical transplantation strategies for patients with transfusion-dependent thalassaemia (TD-TM) remain to be investigated. In this study, 54 paediatric patients with TD-TM were treated with a novel approach using post-transplant cyclophosphamide (PTCy) and low-dose methotrexate (LD-MTX), following a myeloablative regimen. The incidence of neutrophil and platelet engraftment was 96.3% ± 2.6% and 94.4% ± 3.1% respectively. The cumulative incidence of grades II-III acute graft-versus-host disease (GVHD) was 13.8% ± 4.8% at 100 days. At three years, the cumulative incidence of chronic GVHD was 28.5% ± 8.5%. With a median follow-up of 520 days (132-1325 days), the overall survival (OS) and event-free survival (EFS) were 98.1% ± 1.8% and 90.7% ± 3.9% respectively. Compared with the low-dose cyclophosphamide (CTX) conditioning regimen (120 mg/kg), the high-CTX regimen (200 mg/kg) achieved a higher incidence of stable engraftment (100% vs 66.7% ± 15.7%, p = 0.003), a comparable incidence of grades II-III acute GVHD, a lower incidence of chronic GVHD (20.2% ± 8.3% vs 66.6% ± 19.2%, p = 0.011), and better overall survival (100% vs 88.9% ± 10.5%, p = 0.025) as well as EFS (95.6% ± 3.1% vs 66.7% ± 15.7%, p = 0.008). Our results using unmanipulated haploidentical grafts and PTCy with LD-MTX in TD-TM are encouraging. (chictr.org.cn ChiCTR1800017969).

Safety and efficacy of direct oral anticoagulation in patients with and without radiofrequency ablation of non-valvular atrial fibrillation: a multicenter retrospective cohort study.

BACKGROUND: Based on the few available studies on the prognostic benefit of using direct oral anticoagulants (DOACs) after atrial fibrillation (AF) ablation. Therefore, this study aimed to evaluate the prognostic differences between patients who underwent radiofrequency ablation (RFA) and those without RFA taking DOACs. METHODS: This is a multicenter retrospective cohort study enrolling 6137 patients with non-valvular AF (NVAF) at 15 hospitals in China. Patient information was collected through a mean follow-up of 10 months and medical record queries. Clinical outcomes included major bleeding, total bleeding, thrombosis, all-cause death, and a composite endpoint of bleeding, thrombosis, and all-cause death. RESULTS: After adjusting for confounders and propensity score matching (PSM), patients with RFA of NVAF had a significantly lower risk of major bleeding [OR 0.278 (95% CI, 0.150-0.515), P<0.001], thrombosis [OR 0.535 (95% CI, 0.316-0.908), P=0.020] and the composite endpoint [ OR 0.835 (95% CI, 0.710-0.982), P=0.029]. In the RFA PSM cohort, dabigatran was associated with reduced all-cause death in patients with RFA of NVAF [OR 0.420 (95% CI, 0.212-0.831), P=0.010]. In the no RFA PSM cohort, rivaroxaban was associated with a reduction in major bleeding [OR 0.521 (95% CI, 0.403-0.673), P<0.001], total bleeding [OR 0.114 (95% CI, 0.049-0.266), P<0.001], and the composite endpoint [OR 0.659 ( 95% CI, 0.535-0.811), P<0.001]. CONCLUSION: Among patients with NVAF treated with DOACs, RFA was a negative correlate of major bleeding, thrombosis, and composite endpoints but was not associated with total bleeding or all-cause mortality.

Safety and efficacy of direct oral anticoagulants in stroke prevention in patients with atrial fibrillation complicated with anemia and/or thrombocytopenia: a retrospective cohort study.

BACKGROUND: There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia. METHODS: This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male < 130 g/L; female < 120 g/L or platelet < 100 × 109/L), and Group 3 (hemoglobin male < 130 g/L; female < 120 g/L and platelet < 100 × 109/L). Patients in each category are further divided into two groups according to their stroke prevention strategies: rivaroxaban or dabigatran. Clinical results include major, minor, total bleeding, thrombosis, and the composite outcome of major bleeding and thrombosis. RESULTS: Higher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any event. Compared with Group 1, Group 2 had a higher risk of major bleeding (aOR 1.70, 95%CI 1.12-2.57, P = 0.012), and the composite endpoint of major bleeding and thrombosis (aOR 1.70, 95%CI 1.19-2.44, P = 0.004). Compared with Group 1, Group 3 had a higher total bleeding risk (aOR 2.15, 95%CI 1.14-4.05, P = 0.018). Compared with dabigatran, rivaroxaban was associated with higher composite risk in Group 1 (aOR 2.91, 95% CI 1.66-5.16, P < 0.001) and Group 2 (aOR 3.05, 95%CI 1.46-6.39, P = 0.003), but there was no significant difference in Group 3 (aOR 1.78, 95%CI 0.23-13.54, P = 0.577). CONCLUSIONS: Higher hemoglobin levels are associated with a reduced risk of total bleeding and major bleeding in patients with AF. Dabigatran was associated with better clinical outcomes than rivaroxaban in patients with anemia or thrombocytopenia but not in those with anemia and thrombocytopenia.

Association between Body Mass Index and Clinical Outcomes in Patients with Non-valvular Atrial Fibrillation Receiving Direct Oral Anticoagulants: A New Piece of Evidence on the Obesity Paradox from China.

PURPOSE: We conducted a multicenter real-world study in China to assess the association between body mass index (BMI) and clinical outcomes in patients with atrial fibrillation (AF) taking direct oral anticoagulants (DOACs). METHOD: This is a retrospective multicenter cohort study conducted in 15 centers in China. We collected demographic information through the hospital information system and obtained clinical events through follow-up visits to patients or relatives. Clinical outcomes include major, minor, total bleeding, thromboembolism, and all-cause death. RESULT: A total of 6164 patients with non-valvular AF (NVAF) were included in this study. The incidence of major bleeding in patients with NVAF differed significantly by BMI category (P < 0.001), with 5.2% in the underweight group, 2.6% in the normal group, 1.4% in the overweight group, 1.1% in the obese I group, and 1.3% in the obese II group. There was no significant difference in minor, total bleeding, and thrombosis in the five groups (P = 0.493; P = 0.172; P = 0.663). All-cause death was significantly different among the five groups (P < 0.001), with 8.9% in the underweight group, 6.3% in the normal group, 4.8% in the overweight group, 2.2% in the obese I group, and 0.4% in the obese II group. High BMI was negatively associated with major bleeding (OR = 0.353, 95% CI 0.205-0.608), total bleeding (OR = 0.664, 95% CI 0.445-0.991), and all-cause death (OR = 0.370, 95% CI 0.260-0.527). CONCLUSION: In patients with NVAF treated with DOACs, higher BMI was associated with lower major bleeding and better survival. BMI was a negative correlate of total bleeding, but not minor bleeding and thrombosis.

To establish a model for the prediction of initial standard and maintenance doses of warfarin for the Han Chinese population based on gene polymorphism: a multicenter study.

PURPOSE: The purpose of this paper is to study the correlation between demographic and clinical factors and warfarin dose of patients in Chinese Han population taking warfarin and study gene polymorphisms impact of related gene loci (CYP2C9*3, VKORC1-1639G > A) on warfarin doses, to establish a model to predict initial standard dose and maintenance dose based on CYP2C9*3, VKORC1-1639G > A genotype. METHODS: The study collects the data of patients in our hospital and other subcenters which incorporates 2160 patients to establish the initial dose model and 1698 patients for the stable dose model, and sequences 26 multigene sites in 451 patients. Based on the patient's dosage, clinical data, and demographic characteristics, the genetic and non-genetic effects on the initial dose and stable dose of warfarin are calculated by using statistical methods, and the prediction model of initial standard dose and maintenance dose can be established via multiple linear regression. RESULTS: The initial dose of warfarin (mg/day) was calculated as (1.346 + 0.350 × (VKORC1-1639G > A) - 0.273 × (CYP2C9*3) + 0.245 × (body surface area) - 0.003 × (age) - 0.036 × (amine-iodine) + 0.021 × (sex))2. This model incorporated seven factors and explained 55.3% of the individualization differences of the warfarin drug dose. The maintenance dose of warfarin (mg/day) was calculated as (1.336 + 0.299 × (VKORC1-1639G > A) + 0.480 × (body surface area) - 0.214 × (CYP2C9*3) - 0.074 × (amine-iodine) - 0.003 × (age) - 0.077 × (statins) - 0.002 × (height))2. This model incorporated six factors and explained 42.4% of the individualization differences in the warfarin drug dose. CONCLUSION: The genetic and non-genetic factors affecting warfarin dose in Chinese Han population were studied systematically in this study. The pharmacogenomic dose prediction model constructed in this study can predict anticoagulant efficacy of warfarin and has potential application value in clinical practice.

Clinical study on ixazomib in the treatment of multiple myeloma. / ä¼Šæ²™ä½ç±³æ²»ç–—å¤šå‘æ€§éª¨é«“ç˜¤çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To evaluate the efficacy and safety of ixazomib in the treatment of multiple myeloma. METHODS: A total of 43 patients with multiple myeloma were given ixazomib-based chemotherapy, including 16 patients with relapsed/refractory multiple myeloma (RRMM group), 27 patients newly diagnosed multiple myeloma with serious adverse events initially treated with bortezomib (conversion treatment group). Single ixazomib or ixazomib-based 2- or 3-medicine regimens combined with dexamethasone and lenalidomide or thalidomide or cyclophosphamide were performed, and then the response and safety were assessed. RESULTS: The overall response rate (ORR) was 56.25%, and the rate of very good partial response (VGPR) was 18.75% in the RRMM group. Most effective patients were those with long-term recurrence. The ORR was 88.89% in the conversion treatment group, which was further improved compared with the ORR of 81.48% before the conversion, among which 59.26% had a further remission. The main adverse events included thrombocytopenia, leucopenia, diarrhea, asthenia, rash, joint pain, etc. CONCLUSIONS: Lxazomib is effective in treating the patients with later recurrence and the patients with serious adverse events initially treated with bortezomib. Lxazomib may not be effective in patients with recent relapse after bortezomib treatment. The adverse events are controllable.

Multiscale Bidirectional Temporal Convolutional Network for Sleep Apnea Detection Based on Wearable Photoplethysmography Bracelet.

Sleep apnea syndrome (SAS), which can lead to a range of Cardiopulmonary diseases, is a common chronic sleep disorder. The unobtrusive detection based on wearable devices is helpful for early diagnosis and treatment of SAS. To this end, this paper presents a method based on a one-dimensional multi-scale bidirectional temporal convolutional neural network (1D-MsBiTCNet) and two model performance optimization techniques, i.e., regularized dropout (RD) and logit adjustment (LA). Among them, 1D-MsBiTCNet has outstanding capabilities in both feature extraction and temporal dependence representation. RD and LA play an effective role in solving the overfitting problem of model training and the class imbalance problem of the dataset, respectively. The proposed model was trained and tested on a photoplethysmography (PPG) dataset (including data from 92 subjects) collected from commercial wearable bracelets. On this dataset, our method achieved accuracy, sensitivity and specificity of 82.76%, 71.58%, 86.74% for per-segment detection, and 97.83%, 88.89%, 100.00% for per-recording severe SAS detection. For the precise quantification of apnea-hypopnea index (AHI), our method achieved a mean absolute error of 5.44 between the predicted AHI and the ground truth AHI. The experimental results show that our proposed method has an outstanding performance and can provide a methodological reference for large-scale SAS automatic detection.

Explainable Machine Learning-Based Prediction Model for Diabetic Nephropathy.

The aim of this study is to analyze the effect of serum metabolites on diabetic nephropathy (DN) and predict the prevalence of DN through a machine learning approach. The dataset consists of 548 patients from April 2018 to April 2019 in the Second Affiliated Hospital of Dalian Medical University (SAHDMU). We select the optimal 38 features through a least absolute shrinkage and selection operator (LASSO) regression model and a 10-fold cross-validation. We compare four machine learning algorithms, including extreme gradient boosting (XGB), random forest, decision tree, and logistic regression, by AUC-ROC curves, decision curves, and calibration curves. We quantify feature importance and interaction effects in the optimal predictive model by Shapley additive explanation (SHAP) method. The XGB model has the best performance to screen for DN with the highest AUC value of 0.966. The XGB model also gains more clinical net benefits than others, and the fitting degree is better. In addition, there are significant interactions between serum metabolites and duration of diabetes. We develop a predictive model by XGB algorithm to screen for DN. C2, C5DC, Tyr, Ser, Met, C24, C4DC, and Cys have great contribution in the model and can possibly be biomarkers for DN.

[Preliminary screen of metastasis-related genes in cervical squamaous cell carcinoma].

OBJECTIVE: To explore the differentially expressed gene profile in cervical squamous cell carcinoma tissues with and without pelvic lymph node metastasis by microarray technique and to screen tumor metastasis-related genes. METHODS: Cancer tissue samples were collected from 4 cervical squamous cell carcinoma patients with pelvic lymph metastasis and 6 patients without metastasis before the treatment. Differentially expressed gene profile was identified between cervical squamous cell carcinoma tissues with and without pelvic lymph node metastasis by NimbleGen microarray. Fluorescent real-time quantitative PCR was employed to validate the accuracy of the microarray by detecting the expression of genes picked from the differentially expressed gene profile. We screened tumor metastasis-related genes through the gene bank, PUBMED and gene ontology analysis. RESULTS: With the application of microarray, 329 genes were identified as markedly differentially expressed genes between cervical squamous cell carcinoma tissues with and without pelvic lymph node metastasis. Real-time PCR was in accordance with microarray. Forty-four genes associated with tumor metastasis were identified from the differentially expressed gene profile. CONCLUSION: Gene profile in cervical squamous cell carcinoma tissues associated with pelvic lymph node metastasis is preliminarily identified, indicating that lymph node metastasis of cervical squamous cell carcinoma is a process involving numerous genes.

MS-Net: Sleep apnea detection in PPG using multi-scale block and shadow module one-dimensional convolutional neural network.

Sleep Apnea (SA) is a respiratory disorder that affects sleep. However, the SA detection method based on polysomnography is complex and not suitable for home use. The detection approach using Photoplethysmography is low cost and convenient, which can be used to widely detect SA. This study proposed a method combining a multi-scale one-dimensional convolutional neural network and a shadow one-dimensional convolutional neural network based on dual-channel input. The time-series feature information of different segments were extracted from multi-scale temporal structure. Moreover, shadow module was adopted to make full use of the redundant information generated after multi-scale convolution operation, which improved the accuracy and ensured the portability of the model. At the same time, we introduced balanced bootstrapping and class weight, which effectively alleviated the problem of unbalanced classes. Our method achieved the result of 82.0% average accuracy, 74.4% average sensitivity and 85.1% average specificity for per-segment SA detection, and reached 93.6% average accuracy for per-recording SA detection after 5-fold cross validation. Experimental results show that this method has good robustness. It can be regarded as an effective aid in SA detection in household use.

Causal inference between rheumatoid arthritis and prostate cancer.

It is unclear if the association between rheumatoid arthritis (RA) and a higher risk of prostate cancer (Pca) reflects a causal relationship. We conducted a meta-analysis and used the Mendelian randomization method (MR) to evaluate the association between RA and Pca risk. A meta-analysis and subgroup analysis of the incidence of Pca in patients with RA was conducted. To determine whether genetically elevated RA levels were causally linked to Pca, two MR samples were employed. To eliminate gender-related bias, we conducted a stratified analysis of the GWAS data for RA by gender, specifically including 140,254 males. Additional MR analysis was also performed to determine potential confounding factors influencing the association between genetically susceptible RA and Pca. In total, 409,950 participants were enrolled in 20 trials to investigate the Pca risk in patients with RA. The meta-analysis suggested that RA was unrelated to the Pca risk (SIR = 1.072, 95% CI, 0.883-1.261). However, a subgroup analysis showed that low smoking rates might increase the Pca risk in patients with RA by 24%. The MR analysis showed that increased genetic susceptibility to RA was related to a high Pca risk (OR = 36.20, 95%CI = 1.24-1053.12, P = 0.037). The causality estimation of MR-Egger, Weighted mode, Simple mode, and Weighted median method were similar in direction and magnitude. Although our meta-analysis found no correlation between RA and Pca risk, MR analyses supported a causal relationship between genetic susceptibility to RA and increased prostate risk. Early attention to Pca risk in patients with RA may be important for improving prognosis and mortality in such patients. Further research is needed to determine the etiology of RA attributed to Pca and its underlying mechanisms.

Hemophagocytic lymphohistiocytosis as an onset of diffuse large B-cell lymphoma: A case report.

A 53-year-old male presented with a 1-month history of hyperpyrexia. The clinical manifestations revealed hemophagocytic lymphohistiocytosis (HLH). Although a lymph node biopsy could not be obtained, a bone marrow biopsy revealed the activated B-cell subtype of diffuse large B-cell lymphoma (DLBCL). After being treated with HLH-1994 (dexamethasone and etoposide), a rituximab-containing chemotherapy and target agents involving bortezomib, the patient achieved remission. To understand the molecular profile of patient, next-generation sequencing and MYD88 L265P mutation examinations were performed, and the patient was determined to be positive for the MYD88 L265P mutation. Reports of DLBCL with plasmacytic differentiation and a MYD88 innate immune signal transduction adaptor L265P mutation concurrent with HLH are rare. Early recognition, precise diagnosis and timely therapy are pivotal in improving patient prognosis. Furthermore, molecular profiling enables researchers to develop potential therapies aimed at the activated NF-κB and endoplasmic reticulum stress signaling pathways. The present study highlights this pathogenesis and provides suggestions for further individualized therapeutics.

Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nests.

BACKGROUND: The differentiation of human induced pluripotent stem cells (iPSCs) into oocytes, which involves the transformation from mitosis to meiosis, has been a hotspot of biological research for many years and represents a desirable experimental model and potential strategy for treating infertility. At present, studies have shown that most cells stagnate in the oogonium stage after differentiation into primordial germ cells (PGCs) from human iPSCs. METHODS: iPSCs carrying a SYCP3-mkate2 knock-in reporter were generated by the CRISPR/Cas9 strategy to monitor meiosis status during induced differentiation from iPSCs into oocytes. These induced PGCs/oogonia were activated by small molecules from the Wnt signaling pathway and then cocultured with reconstructed human ovarian nests in vivo for further development. RESULTS: First, human PGCs and oogonia were efficiently induced from iPSCs. Second, induced dormant PGCs resumed meiosis and then differentiated into primary oocytes through the in vitro activation of the Wnt signaling pathway. Finally, a new coculture system involving the reconstruction of ovarian nests in vitro could facilitate the differentiation of oocytes. CONCLUSIONS: Human PGCs/oogonia induced from iPSCs can be activated and used to resume meiosis by molecules of the Wnt signaling pathway. The coculture of activated PGCs and reconstruction of ovarian nests facilitated differentiation into primary oocytes and the generation of haploid human oocytes in vivo. These findings established a new strategy for germline competence in primary oocytes and provided a keystone for human gametogenesis in vitro and in vivo.

Obstructive sleep apnea detection from single-lead electrocardiogram signals using one-dimensional squeeze-and-excitation residual group network.

Obstructive sleep apnea (OSA), which has high morbidity and complications, is diagnosed via polysomnography (PSG). However, this method is expensive, time-consuming, and causes discomfort to the patient. Single-lead electrocardiogram (ECG) is a potential alternative to PSG for OSA diagnosis. Recent studies have successfully applied deep learning methods to OSA detection using ECG and obtained great success. However, most of these methods only focus on heart rate variability (HRV), ignoring the importance of ECG-derived respiration (EDR). In addition, they used relatively simple networks, and cannot extract more complex features. In this study, we proposed a one-dimensional squeeze-and-excitation (SE) residual group network to thoroughly extract the complementary information between HRV and EDR. We used the released and withheld sets in the Apnea-ECG dataset to develop and test the proposed method, respectively. In the withheld set, the method has an accuracy of 90.3%, a sensitivity of 87.6%, and a specificity of 91.9% for per-segment detection, indicating an improvement over existing methods for the same dataset. The proposed method can be integrated with wearable devices to realize inexpensive, convenient, and highly efficient OSA detectors.

Chidamide-Induced Accumulation of Reactive Oxygen Species Increases Lenalidomide Sensitivity Against Multiple Myeloma Cells.

BACKGROUND: Lenalidomide, an immunomodulatory drug (IMiD), is an effective therapy for the treatment of multiple myeloma (MM). However, prolonged treatment may be accompanied by toxicity, second primary malignancies, and drug resistance. There is an inherent vulnerability in MM cells that high rates of immunoglobulin synthesis resulting in the high level of reactive oxygen species (ROS). This provides a therapeutic potential for MM. MATERIALS AND METHODS: The intracellular ROS levels, H2O2 production and glutathione (GSH) levels were measured using detection kit. Cell viability was evaluated using cell-counting kit-8 (CCK-8) and soft agar colony formation assay. Apoptosis was determined in whole living cells using flow cytometry. Chidamide and its anti-myeloma efficacy in combination with lenalidomide were characterized in MM cell lines in vitro and in a mouse xenograft model. Moreover, Western blotting, immunofluorescence and immunohistochemical studies were performed. RESULTS: ROS levels increased in a time- and dose-dependent manner with chidamide treatment. Moreover, the GSH levels were decreased and the mRNA level of SLC7A11 downregulated after chidamide treatment. The co-treatment with chidamide and lenalidomide increased apoptosis and proliferation inhibition, with combination index (CI) in the synergistic range (0.2-0.5) using the Chou-Talalay method. The cooperative anti-myeloma efficacy was confirmed in the murine model, and immunohistochemical studies also supported this potentiation. Chidamide enhanced the effect of lenalidomide-induced degradation of IKZF1 and IKZF3 by elevating H2O2. In addition, co-treatment with chidamide and lenalidomide increased biomarkers of caspase and DNA damage. CONCLUSION: Elevated ROS production may constitute a potential biochemical basis for anti-myeloma effects of chidamide plus lenalidomide. The results of this study confirm the synergistic effect of chidamide and lenalidomide against MM and provide a promising therapeutic strategy for MM.

Loss of the ClpXP Protease Leads to Decreased Resistance to Cell-Envelope Targeting Antimicrobials in Bacillus anthracis Sterne.

The ClpX ATPase is critical for resistance to cell envelope targeting antibiotics in Bacillus anthracis, however, it is unclear whether this is due to its function as an independent chaperone or as part of the ClpXP protease. In this study, we demonstrate that antibiotic resistance is due to formation of the ClpXP protease through construction of a ClpX complementation plasmid that is unable to interact with ClpP. Additionally, we genetically disrupted both clpP genes, clpP1 and clpP2, found in B. anthracis Sterne and find that the loss of either increases susceptibility to cell envelope targeting antimicrobials, although neither has as strong of a phenotype as loss of clpX and neither clpP gene is essential for virulence in a G. mellonella model of infection. Lastly, we looked at changes to cell envelope morphology that could contribute to increased antibiotic sensitivity. We find no difference in cell charge or cell lysis, although we do see increased hydrophobicity in the ΔclpX strain, decreased cellular density and slightly thinner cells walls. We also see significant cell division defects in ΔclpX, although only when cells are grown in the mammalian cell culture medium, RPMI. We conclude that the intrinsic resistance of B. anthracis to cell wall active antimicrobials is dependent on formation of the ClpXP protease and that this could be due, at least in part, to the role of ClpX in regulating cell envelope morphology.

Chidamide, a subtype-selective histone deacetylase inhibitor, enhances Bortezomib effects in multiple myeloma therapy.

Drug resistance is the major cause for disease relapse and patient death in multiple myeloma (MM). It is an urgent need to develop new therapies to overcome drug resistance in MM. Chidamide (CHI), a novel oral HDAC inhibitor targeting HDAC1, 2, 3 and 10, has shown potential therapeutic effect in MM. In this study, we determined that CHI exhibited significant anti-tumor effect on MM cells both in vitro and in vivo, which was positively correlated with the expression of HDAC1. Meanwhile, CHI enhanced Bortezomib (BTZ) effects synergistically in MM cells and a combination of CHI with BTZ induced myeloma cell apoptosis and G0/G1 arrest in vitro and in vivo. Mechanistically, the synergistic anti-tumor effect of CHI and BTZ was related with the increased production of reactive oxygen species (ROS) dependent DNA damage and the changes of cell apoptosis and cycle pathways. Our data indicate that CHI may be a suitable drug to sensitize BTZ in MM cells, which provides novel insight into the therapy for MM patients.

Spatial imputation for air pollutants data sets via low rank matrix completion algorithm.

Incomplete observation of hourly air-pollutants concentration data is a common issue existing in urban air quality monitoring networks. This research proposes a spatial interpolation method to impute missing values presented in air pollutants data sets based on low rank matrix completion (LRMC). It considers air pollutants data of high correlation and consistency in its spatial distribution. We evaluate the performance of the proposed method when imputing various air pollutants concentration time series (NOx,O3,SO2,PM2.5,PM10) in terms of root mean square error (RMSE), index of agreement (D2), and goodness of fit (R2). It systematically compared with existing established imputation techniques, including nearest neighboring, mean substitution, regression-based method, spline interpolation, spectral method, and regularized expectation maximization algorithm (EM). As a spatial imputation method, LRMC outperforms these methods used in this research under the condition of larger missing ratio (such as 30% removal) on the central air pollutants monitoring station. For all monitoring stations, comprehensive experimental results show that LRMC always generates robust results to replace missing data with reasonable substitutions, and it is not sensitive to the length of missing gaps. The promising imputation performance in terms of the indicator R2 obtained by the proposed LRMC demonstrates that it can effectively impute missing values of air pollutants time series based on their inherent patterns.

A Possible Reason to Induce Acute Graft-vs.-Host Disease After Hematopoietic Stem Cell Transplantation: Lack of Sirtuin-1 in CD4+ T Cells.

Sirtuin 1 (SIRT1) is a critical suppressor of T cell immunity. However, whether SIRT1 is involved in the progression of acute graft-vs.-host disease (aGVHD) has still remained unclear. PI3K/Akt/mTOR pathway is a crucial element involved in the activation and functions of T cells. Over-activation of PI3K/Akt/mTOR signaling may be related to the occurrence of aGVHD. STAT3 activation requires phosphorylation and acetylation. A recent study showed that STAT3 hyperphosphorylation in CD4+ T cells may be a trigger of aGVHD. The role of the STAT3 acetylation in aGVHD pathogenesis is still unclear. The present study revealed that SIRT1 deficiency as a critical factor is involved in the excessive activation of mTOR pathway and upregulation of STAT3 acetylation and phosphorylation in CD4+ T cells from patients with aGVHD. Exorbitant activation of IL-1ß signaling is the main reason for TAK1-dependent SIRT1 insufficiency. The findings of the present study might provide a new therapeutic target for treating aGVHD.