Free nitrous acid prediction in ANAMMOX process using hybrid deep neural network model.

Free nitrous acid (FNA) is a critical metric for stabilization of ANAMMOX but can not be directly and immediately measured by sensors or chemical measurement method, which hinders the effective management and operation for ANAMMOX. This study focuses on FNA prediction using hybrid model based on temporal convolutional network (TCN) combined with attention mechanism (AM) optimized by multiobjective tree-structured parzen estimator (MOTPE), called MOTPE-TCNA. A case study in an ANAMMOX reactor is carried out. Results show that nitrogen removal rate (NRR) is highly correlated with FNA concentration, indicating that it can forecast the operational status by predicting FNA. Then, MOTPE successfully optimizes the hyperparameters of TCN, helping TCN achieve a high prediction accuracy, and AM furtherly improves model accuracy. MOTPE-TCNA obtains the highest prediction accuracy, whose R2 value gets 0.992, increasing 1.71-11.80% compared to other models. As a deep neural network model, MOTPE-TCNA has more advantages than traditional machine learning methods in FNA prediction, which is beneficial to maintain the stable operation and easy control for ANAMMOX process.

Accurate prediction and further dissection of neonicotinoid elimination in the water treatment by CTS@AgBC using multihead attention-based convolutional neural network combined with the time-dependent Cox regression model.

Imidacloprid (IMI), as the most widely used neonicotinoid insecticide, poses a serious threat to the water ecosystem due to the inefficient elimination in the traditional water treatment. Chitosan (CTS)-stabilized biochar (BC)-supported Ag nanoparticles (CTS@AgBC) are applied to eliminate the IMI in the water treatment effectively. Batch experiments depict that the modification of BC by CTS and Ag nanoparticles remarkably improve its adsorption performance. The pseudo-second-order and Elovich models have good performance in simulating the adsorption processes of CTS@AgBC and BC. This indicates that the chemical adsorption on real surfaces plays the dominant role in the adsorption of IMI by CTS@AgBC and BC. In addition, the multihead attention (MHA)-based convolutional neural network (CNN) combined with the time-dependent Cox regression model are initially applied to predict and dissect the adsorption elimination processes of IMI by CTS@AgBC. The proposed MHA-CNN model achieves more accurate concentration prediction of IMI than traditional models. According to influence weights by MHA module, biochar category, pH, and treatment temperature are considered the three dominant environmental variables to determine the IMI elimination processes. This study provides insights into roles of environmental variables in the elimination of IMI by CTS@AgBC and the accurate prediction of IMI concentration.

Mycobacterium tuberculosis 19-kDa lipoprotein induces Toll-like receptor 2-dependent peroxisome proliferator-activated receptor γ expression and promotes inflammatory responses in human macrophages.

Mycobacterium tuberculosis (M.tb) enhances its survival in macrophages by suppressing immune responses, in part through its complex cell wall structures. M.tb 19­kDa lipoprotein (P19), a component of the complex cell wall structures of M.tb, is a Toll­like receptor (TLR) agonist, and may induce immune responses through TLR2. Furthermore, the activation of peroxisome proliferator­activated receptor γ (PPARγ) is also involved in M.tb­induced immune responses in macrophages. In the present study, specific agonists/antagonists and siRNA were used to investigate the role of PPARγ in P19­induced immune responses in human macrophages, including TLR2 activation, p38 phosphorylation and cytokine production. In the present study, PPARγ expression, p38 phosphorylation and cytokine production were upregulated following M.tb H37Rv infection or P19 treatment. By pretreating macrophages with a specific PPARγ agonist or antagonist, it was demonstrated that phosphorylation and IL­6 production are modulated in macrophages by PPARγ activity. Following TLR2 knockdown in macrophages, the expression of PPARγ was significantly decreased in the presence or absence of P19 treatment. Furthermore, p38 phosphorylation and cytokine production were significantly reduced in TLR2 knockdown macrophages following P19 treatment. It was demonstrated in the current study that PPARγ was induced and activated by M.tb infection and that P19­induced PPARγ expression, p38 phosphorylation and cytokine production in macrophages are dependent on TLR2. These findings suggest a role for PPARγ and TLR2 in P19­induced p38 phosphorylation and cytokine production, thereby potentially influencing M.tb pathogenesis.

[The effects of curcumin on the 19 000 Mycobacterium tuberculosis protein-induced inflammatory and apoptotic reaction and the expression of p38 mitogen-activated protein kinases in WBC264-9C macrophages].

OBJECTIVE: By using the cell wall component of Mycobacterium tuberculosis 19 000 lipoprotein (P19) and curcumin (CUR) acting on the human macrophage cell line WBC264-9C, and by the blocking of the p38 mitogen-activated protein kinases (p38 MAPK) signaling pathway, we wanted to investigate the effect of curcumin on P19-induced inflammatory responses and apoptosis in human macrophages and the potential underlying molecular mechanisms. METHODS: P19 and CUR were used to stimulate human macrophages for 48 h. Their effects on growth inhibition and on apoptosis in macrophages were observed. The combination effect of CUR with P19 on the expression of IL-1ß, IL-6, TNF-α, STAT3, P53, Bax, Bcl2 and phspho-p38 MAPK levels were also observed. By using the antagonist of p38 MAPK, the effect of CUR on P19-induced expression of inflammatory cytokines and apoptotic proteins were investigated. RESULTS: Twenty and 40 µmol/L of CUR inhibited the growth of macrophages by (10.1 ± 2.3)% and (19.0 ± 2.7)%. The growth inhibition rate of macrophages in the controls, P19 and P19+CUR treated groups were (6.7 ± 4.2)%, (45.4 ± 3.6)% and (32.1 ± 3.0)%, respectively. The P19-induced growth inhibition was significantly attenuated by CUR treatment (q = 9.75, P < 0.01). The expression of IL-1ß, IL-6, TNF-α and STAT3 mRNA (13.2 ± 2.7, 33.5 ± 1.1, 3.3 ± 2.2, 0.9 ± 1.7) were significantly lower than P19-treated groups (21.8 ± 3.5, 14.3 ± 1.4, 6.1 ± 3.6, 4.5 ± 3.4) (q values were ranged from 7.18 to 3.22, all P < 0.05). Furthermore, P53 protein (94.3 ± 0.2; q = 7.05, P < 0.01) and Bax (70.8 ± 8.7; q = 7.66, P < 0.01) levels were decreased in CUR+P19 group as compared with P19 group (320.2 ± 0.2 and 182.6 ± 1.2). Blockade of p38 MAPK accompanied with CUR and P19 induced significantly lower levels of IL-6 mRNA (34.9 ± 1.5, q = 2.36, P < 0.05) and Bax/Bcl2 protein (0.36 ± 0.09; q = 3.50, P < 0.05) expression, as compared with the controls (69.9 ± 1.8 and 0.71 ± 0.11). CONCLUSIONS: P19 increased the expression of inflammatory cytokines and promoted the apoptosis of macrophages possibly through the activation of p38 MAPK signaling pathway. Low concentration of curcumin may play a protective effect against P19-induced immune responses by inhibiting the p38 MAPK pathway in macrophages.

Diagnostic accuracy of intracellular mycobacterium tuberculosis detection for tuberculous meningitis.

RATIONALE: Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity. OBJECTIVES: We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis. METHODS: Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6-expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients' final diagnosis. MEASUREMENTS AND MAIN RESULTS: Two hundred and eighty patients with suspected tuberculous meningitis were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6-6.7%), compared with 82.9% (95% confidence interval, 77.4-87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8-80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4-93.8%) and 90.0% (95% confidence interval, 75.4-96.7%), respectively. CONCLUSIONS: Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis.