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Illicit discharges into sewer systems are a widespread concern within China's urban drainage management. They can result in unforeseen environmental contamination and deterioration in the performance of wastewater treatment plants. Consequently, pinpointing the origin of unauthorized discharges in the sewer network is crucial. This study aims to evaluate an integrative method that employs numerical modeling and statistical analysis to determine the locations and characteristics of illicit discharges. The Storm Water Management Model (SWMM) was employed to track water quality variations within the sewer network and examine the concentration profiles of exogenous pollutants under a range of scenarios. The identification technique employed Bayesian inference fused with the Markov chain Monte Carlo sampling method, enabling the estimation of probability distributions for the position of the suspected source, the discharge magnitude, and the commencement of the event. Specifically, the cases involving continuous release and multiple sources were examined. For single-point source identification, where all three parameters are unknown, concentration profiles from two monitoring sites in the path of pollutant transport and dispersion are necessary and sufficient to characterize the pollution source. For the identification of multiple sources, the proposed SWMM-Bayesian strategy with improved sampling is applied, which significantly improves the accuracy.

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OBJECTIVE: Anaplastic astrocytoma (AA) is an uncommon primary brain tumor with highly variable clinical outcomes. Our study aimed to develop practical tools for clinical decision-making in a population-based cohort study. METHODS: Data from 2997 patients diagnosed with AA between 2004 and 2015 were retrospectively extracted from the Surveillance, Epidemiology, and End Results database. The Least Absolute Shrinkage and Selection Operator and multivariate Cox regression analyses were applied to select factors and establish prognostic nomograms. The discriminatory ability of these nomogram models was evaluated using the concordance index and receiver operating characteristic curve. Risk stratifications were established based on the nomograms. RESULTS: Selected 2997 AA patients were distributed into the training cohort (70%, 2097) and the validation cohort (30%, 900). Age, household income, tumor site, extension, surgery, radiotherapy, and chemotherapy were identified as independent prognostic factors for both overall survival (OS) and cancer-specific survival (CSS). In the training cohort, our nomograms for OS and CSS exhibited good predictive accuracy with concordance index values of 0.752 (95% CI: 0.741-0.764) and 0.753 (95% CI: 0.741-0.765), respectively. Calibration and decision curve analyses curves showed that the nomograms demonstrated considerable consistency and satisfactory clinical utilities. With the establishment of nomograms, we stratified AA patients into high- and low-risk groups, and constructed risk stratification systems for OS and CSS. CONCLUSIONS: We constructed two predictive nomograms and risk classification systems to effectively predict the OS and CSS rates in AA patients. These models were internally validated with considerable accuracy and reliability and might be helpful in future clinical practices.

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Ventilation is paramount in sanitary and stormwater sewer systems to mitigate odor problems and avert pressure surges. Existing numerical models have constraints in practical applications in actual sewer systems due to insufficient airflow modeling or suitability only for steady-state conditions. This research endeavors to formulate a mathematical model capable of accurately simulating various operational conditions of sewer systems under the natural ventilation condition. The dynamic water flow is modeled using a shock-capturing MacCormack scheme. The dynamic airflow model amalgamates energy and momentum equations, circumventing laborious pressure iteration computations. This model utilizes friction coefficients at interfaces to enhance the description of the momentum exchange in the airflow and provide a logical explanation for air pressure. A systematic analysis indicates that this model can be easily adapted to include complex boundary conditions, facilitating its use for modeling airflow in real sewer networks. Furthermore, this research uncovers a direct correlation between the air-to-water flow rate ratio and the filling ratio under natural ventilation conditions, and an empirical formula encapsulating this relationship is derived. This finding offers insights for practical engineering applications.

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As an important component of the deep tunnel drainage system for dealing with urban waterlogging, the rotating stepped dropshaft has been proposed due to its small air entrainment. However, the hydraulic characteristics inside the shaft still need to be fully studied. In this study, the flow patterns, water velocity, and pressure in the rotating stepped dropshaft under different flow rates and geometric parameters were studied using a three-dimensional numerical model. The results show that increasing the central angle of the step and reducing the step height can both reduce the terminal velocity. A theoretical formula for predicting the terminal velocity was established and well validated. The connection between the shaft and the outlet pipe poses a severe threat to the structural safety due to alternating positive and negative pressures. Wall-attached swirling flow generates a circular high-pressure zone at the bottom of the dropshaft and the larger the flow rate, the greater the pressure gradient at the center of the bottom. By using the momentum theorem and considering the impact pressure range of the swirling flow, the shaft bottom pressure can be predicted reasonably well.

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The strategy to enhance phosphor stability against thermal quenching and moisture conditions will contribute to controlling the feature of phosphor-converted white-light-emitting diodes (pc-WLEDs). Herein, an effective strategy is achieved with the incorporation of Sm3+ ions, and a robust reddish-orange emission (no thermal quenching up to 498 K) is obtained based on Ba3LaNb3O12 as a host. In light of excitation by near-ultraviolet irradiation at 408 nm, Ba3LaNb3O12:Sm3+ gives rise to a typical signal ascribed to the 4G5/2 → 6HJ/2 (J = 5, 7, 9, and 11) transitions of Sm3+ ions. The concentration quenching effect is observed when the Sm3+ content exceeds 10%, and the quenching mechanism is caused by electronic dipole-dipole interactions. Based on the narrow emission curves, a very high color purity (92.4%) could be recorded. The Sm3+ substitution at the Ba2+/La3+ site leads to a rigid structural lattice and abundant electron-trapping centers for the Sm3+ ions, which will be responsible for the zero-thermal-quenching phenomenon. In addition, oleic acid (OA) is selected to form a hydrophobic covering surface structure to protect Ba3LaNb3O12:Sm3+, which can assist in improving the moisture resistance. The most favorable parameters concerning the warm-light emission (a high general color rendering index, Ra, of 85.7 and a low correlated color temperature, CCT, of 4965 K) can be achieved in pc-WLEDs containing an OA-modified sample. Moreover, its luminous efficiency, LE, can maintain 82.9% of its initial value after 120 h under controlled environmental conditions of 85 °C and 85% humidity. These results pave a new way to optimize the sample as a potential candidate for red-emitting materials.

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Plunge dropshafts are widely used in urban drainage systems, but they can carry large amounts of air into the system, endangering the safety of the system. In this paper, a 3D numerical model is established to investigate the water flow configuration and air characteristics in a helicoidal ramp dropshaft. The simulations under different outlet pressures and water flow rates were simulated, and the results show that the air demand decreases with the increase of outlet pressure, especially in the case of low water flow. In the case of higher outlet pressure, the air demand first increases then decreases with the increase of the water flow rate. The dragging force of water has little effect on the pressure gradient in the dropshaft. The increase of ramp turns leads to the increase of terminal velocity at the same flow rate, and the air demand first increases and then decreases with the increase of ramp turns.

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The influence of temperature on a variety of physiological or chemical processes has generated considerable interest, and recently noninvasive lanthanide-incorporated optical thermometers have been considered as promising candidates for monitoring its changes at different scales. Herein, a novel Bi3+-activated Sr3-xGdxGaO4+xF1-x phosphor with tunable color has been constructed by a cooperative cation-anion substitution strategy with to the replacement of [Sr2+-F-] by [Gd3+-O2-]. When x = 0, the sample Sr3GaO4F/Bi3+ possesses a peak wavelength at 438 nm, and this value will shift to 470 nm if x is equal to 1 (Sr2GdGaO5/Bi3+). In addition, photoluminescence tuning from blue to red has been realized successfully by an efficient Bi3+ → Eu3+ energy migration model in Sr2.6Gd0.4GaO4.4F0.6 samples. The specific Bi3+ → Eu3+ energy transfer has been explained by dipole-dipole interactions derived from a model of the Dexter pathway. Intriguingly, the two dopants (a blue signal from Bi3+ and a red signal from Eu3+) possess different thermal responses to increasing temperature. Accordingly, the intensity ratio values are sensitive to the temperature changes. The energy level cross relaxation causes the quenching effect of Bi3+, and the multi-phonon de-excitation mode leads to the thermal quenching of Eu3+. At room temperature (298 K), the determined maximum relative sensitivity (Sr) is 1.27% K-1. Moreover, the absolute sensitivity (Sa) is 0.067 K-1 since the temperature is elevated to 523 K. The collected results are superior to most of the reported optical thermometry materials.

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In recent years, PD-1 immune checkpoint inhibitors based on monoclonal antibodies have revolutionized cancer therapy, but there still exist unresolved issues, such as the high cost, the relatively low response rates, and so on, compared with small-molecule drugs. Herein a type of pyrrole-imidazole (Py-Im) polyamide as a small-molecule DNA binder was designed and synthesized, which could competitively bind to the same double-stranded DNA stretch in the PD-L1 promoter region as the STAT3 binding site and thus downregulate PD-L1 expression. It was demonstrated that the Py-Im polyamides directly caused apoptosis in tumor cells and retarded cell migration in the absence of T cells through inhibiting the Akt/caspase-3 pathway. Also, in a coculture system, they enhanced the T-cell-mediated killing of tumor cells by the reversal of immune escape. Because such polyamides induced antitumor effects via both immune and nonimmune pathways, they could be further developed as promising PD-L1 gene-targeting antitumor drugs.

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Storm geysers increasingly occur in sewer systems under climate change and rapid urbanization. Mitigation measures are in great demand to avoid safety problems. In this study, three-dimensional computational fluid dynamics models of single-inlet and multi-inlet systems were established to investigate geysering induced by rapid filling and assess the effectiveness of potential mitigation methods. The modeling results suggest that increasing the capacity of the downstream pipe before the inflow front reaches the chamber can effectively reduce the maximum geyser pressure. The peak pressure can be significantly mitigated when the chamber size is designed with care and the drop height between the upstream and downstream pipes is reduced. A diversion deflector with air vents and an orifice plate at the riser top end can alleviate the maximum pressure by about 65% with about 75% of the entrapped air being released. The peak pressure during the geyser event in the multi-inlet model is less than that of a single-inlet model under the same total inflow condition, but more water can be released.

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Rapid filling in horizontal partially filled pipes with entrapped air may result in extreme pressure transients. This study advanced the current understanding of dynamic behavior of entrapped air above tailwater (the initial water column with a free surface in a partially filled pipe) through rigid-column modeling and sensitivity analysis of system parameters. Water and air were considered as incompressible fluid and ideal gas, respectively, and the continuity and momentum equations for water and a thermodynamic equation for air were solved by using the fourth order Runge-Kutta method. The effects of system parameters were examined in detail, including tailwater depth, entrapped air volume, driving head, pipe friction, and relative length of entrapped air and pipe. The results indicate that the presence of tailwater can mitigate the peak pressure when with identical initial volumes of entrapped air, as it can be considered to reflect a certain amount of loss of the net driving head. However, the peak pressure can increase as much as about 45% for the cases with fixed pipe length, due to the reduction in the initial entrapped air volume. The rise time for the first peak pressure was closely related to pipe friction, whereas the oscillation period (defined as the time duration between the first and second peaks) was virtually irrelevant. The applicability of the rigid-column model was discussed, and a time scale relevant indicator was proposed. When the indicator is larger than 20, the relative difference between the peak pressure estimation and experimental measurements is generally below 5%.

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Subdural contrast effusion secondary to endovascular treatment is exceptionally rare and might be mistaken as subdural hematoma because of similar hyperattenuation on computer tomography. The authors present the case of a 13-month-old girl with a history of increased head circumference and developmental retardation. Cerebral digital subtraction angiography showed a high-flow pial arteriovenous fistula fed by multiple arteries on the right cerebellar surface, with occlusion of the right sigmoid sinus and severe stenosis of the left sigmoid sinus. Staged endovascular treatments were performed to eliminate the fistula. Follow-up head computer tomography scans performed 3 h after both procedures demonstrated typical high-density subdural effusion with computer tomography attenuation value similar to hemorrhage. These effusions did not aggravate the condition and disappeared spontaneously 32 h after the first treatment and 29 h after the second, respectively.

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In our work, 19 novel 4,5-diazafluorene derivatives (11a-d, 12a-d, 13a-d, 14a-c, 15c, 16a-c) bearing a 1,3-disubstituted pyrazol/thioxothiazolidinone or thioxothiazolidinone-oxadiazole moieties were designed, synthesized, preliminarily explored for their antitumor activities and in vitro mechanism. All compounds showed different values of antiproliferative activity against A549, AGS, HepG2 and MCF-7 cell lines through CCK-8. Especially, the compound 14c exhibited the strongest activity and best selectivity against A549 cells with an IC50 1.13 µM and an SI value of 7.01 relative to MRC-5 cells, which was better than cisplatin (SI = 1.80) as a positive control. Experimental results at extracellular level demonstrated that compounds 14a-c could strongly interact with the G-quadruplex(es) formed in a 26 nt telomeric G-rich DNA, in particular, the 14c exhibits quite strong binding affinity with an association equilibrium constant (KA) of 7.04(±0.16) × 107 M-1 and more than 1000-fold specificity to G4-DNA over ds-DNA and Mut-DNA at the compound/G4-DNA ratio of 1:1. Further trap assay ascertained that compounds 14a-c owned strong inhibitory ability of telomerase activity in A549 cells, suggesting that these compounds have great possibility to target telomeric G-quadruplexes and consequently indirectly inhibit the telomerase activity. In addition, it is worthy of note that the remarkable inhibitory effects of 14a-c on the mobility of tested cancer cells were observed by wound healing assays. Furthermore, molecular docking and UV-Vis spectral results unclose the rationale for the interaction of compounds with such G-quadruplex(es). These results indicate that the growth and metastasis inhibition of cancer cells mediated by these 4,5-diazafluorene derivatives possibly result from their interaction with telomeric G-quadruplexes, suggesting that 4,5-diazafluorene derivatives, especially 14c, possess potential as anticancer drugs.

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At present, cancers have been causing deadly fears to humans and previously unpredictable losses to health. Especially, lung cancer is one of the most common causes of cancer-related mortality accounting for approximately 15% of all cancer cases worldwide. While Non-Small Cell Lung Carcinomas (NSCLCs) makes up to 80% of lung cancer cases. The patient compliance has been weakening because of serious drug resistance and adverse drug effects. Therefore, there is an urgent need for the development of novel structural agents to inhibit NSCLCs. Nitrogen-containing heterocyclic compounds exhibit wide range of biological properties, especially antitumor activity. We reviewed some deadly defects of clinical medicines for the lung cancer therapy and importance of nitrogen based heterocyclic derivatives against NSCLCs. Nitrogen heterocycles exhibit significant antitumor activity against NSCLCs. Nitrogen heterocyclic hybrids could be developed as multi-target-directed NSCLC inhibitors and it is believed that the review is significant for rational designs and new ideas in the development of nitrogen heterocyclic-based drugs.

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At present, diseases resulting from various reasons have been causing deadly fears to humans and previously incogitable losses to health. Meanwhile, the patient compliance has been weakening because of drug resistance and serious drug adverse effects. There is therefore an urgent need for the development of novel structural agents. Rhodanine derivatives have exhibited wide biological activities, as well as significant industrial applications, which suggests that rhodanine heterocycle represents a key structural motif in heterocyclic chemistry and occupies a prominent position in drug discovery. Here, we review some deadly defects of clinical medicines to the therapy of diseases and important advances on rhodanine derivatives in drug researches (e.g. as anti-diabetic, anti-viral, antiinflammatory, anti-microbial, anti-tumor agents and inhibitors for Alzheimer Disease), indicating that rhodanine heterocycle could be used as a significant pharmacophore to develop novel pharmacological active molecules. It is believed that the review is of importance for new ideas in the development of and rational designs of rhodanine-based drugs.

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OBJECTIVES: The objectives of this study were to examine the correlation between the level of serum inflammatory markers and the stability of carotid plaques in patients with ischemic cerebrovascular disease and to assess the ability of each inflammatory marker to identify vulnerable carotid plaques. METHODS: For the early identification of vulnerable carotid plaques, 65 patients with carotid plaques were divided into a stable plaque group (n = 21) and an unstable plaque group (n = 44) according to magnetic resonance imaging characteristics. The unstable plaque group was divided into an unstable unruptured plaque group (n = 29) and an unstable ruptured plaque group (n = 15) according to whether the fibrous cap was ruptured. The levels of serum soluble cluster of differentiation 40 ligand (sCD40L), matrix metalloproteinase (MMP)-9, and MMP-2 were measured by enzyme-linked immunosorbent assay. RESULTS: The levels of serum sCD40L and MMP-9 in the unstable plaque group, the unstable unruptured plaque group and the ruptured plaque group were significantly higher than those in the stable plaque group (P < 0.05). There was no significant difference in the MMP-2 level between the stable plaque group and unstable plaque group (P = 0.056). The MMP-2 levels in the stable plaque group, unstable unruptured plaque group, and ruptured plaque group were not different (P = 0.095). The carotid plaques and the positive rate of MMP-9 of ≥84.09 ng/mL were statistically significant, suggesting increased vulnerability. CONCLUSIONS: Serum levels of sCD40L and MMP-9 are associated with the stability of carotid plaques. Higher levels of serum sCD40L and MMP-9 may suggest that the plaques are vulnerable or have ruptured.

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A novel series of 2-(1H-pyrazol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthrolines were designed, synthesized and evaluated for their antitumor activity against lung adenocarcinoma by CCK-8 assay, electrophoretic mobility shift assay (EMSA), UV-melting study, wound healing assay and docking study. These compounds showed good inhibitory activities against lung adenocarcinoma. Especially compound 12c exhibited potential antiproliferative activity against A549 cell line with the half maximal inhibitory concentration (IC50) value of 1.48 µM, which was a more potent inhibitor than cisplatin (IC50 = 12.08 µM) and leading compound 2 (IC50 = 1.69 µM), and the maximum cell inhibitory rate being up to 98.40%. Moreover, further experiments demonstrated that compounds 12a-d can strongly interact with telomeric DNA to stabilize G-quadruplex DNA with increased ΔTm values from 12.44 to 20.54 °C at a ratio of DNA to compound 1:10. These results implied that growth inhibition of A549 cells mediated by these phenanthroline derivatives is possibly positively correlated to the fact their interaction with telomeric G-quadruplexs.

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This study reports our experience of balloon-in-stent assisted coiling for the treatment of morphologically unfavorable aneurysms located in the internal carotid artery (ICA). From July 2007 to April 2014, twelve patients with twelve aneurysms located in the ICA were coil embolized by simultaneously using balloon and stent assistance. Five aneurysms were ruptured and seven were unruptured. All the aneurysms were overwide (dome-to-neck ratio ⩽1.2) and undertall (aspect ratio ⩽1.2) anatomically. The procedure-related adverse events, clinical and angiographic results were retrospectively analyzed. Intraprocedural aneurysmal bleeding occurred for one unruptured aneurysm but was stopped immediately after the balloon was inflated. Periprocedural thromboembolism occurred for two ruptured aneurysms, leading to death in one patient and severe neurological deficit for the other one. Procedure-related permanent morbidity and mortality rates were 8.3% (1/12) and 8.3% (1/12). Satisfactory (total and subtotal) occlusion was obtained immediately in 11 (91.7%) cases. Nine aneurysms received digital subtraction angiography follow-up (mean 25.1months, range 6-55), and all of them except one were totally obliterated. No aneurysmal bleeding occurred during a mean period of 59.1months, clinical follow-up for eleven patients. Balloon-in-stent assisted coiling might be a therapeutic alternative to prevent growth or rupture of overwide and undertall aneurysms. Nevertheless, it should be used prudently for ruptured ICA aneurysms, for its disadvantage of technical complexity and relatively high rate of adverse events.

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BACKGROUND: An alarming increment in pathogenic resistance to existing anti-microbial agents is a serious problem and the treatment of these bacterial infections is becoming increasingly challenging. Therefore, there is an urgent need to develop novel antimicrobial agents. OBJECTIVE: As a part of our ongoing studies toward the development of novel antibacterial agents, the synthesis and antibacterial activity of a series of (Z)-5-((3-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one derivatives will be discussed in this study. METHOD: (Z)-5-((3-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one derivatives were designed, synthesized and evaluated for antibacterial activity. The structures were confirmed by IR, 1H NMR, 13C NMR and mass spectrometry. All of the synthesized compounds were evaluated in vitro using a 96-well microtiter plate and a serial dilution method to obtain their minimum inhibitory concentration (MIC) values against a variety of different strains, including multidrug-resistant clinical isolates. RESULTS: The antibacterial test in-vitro showed that most compounds in series 7 and 9 exhibited significant inhibitory activities against anaerobic bacteria (Streptococcus mutans) strains with a MIC value of 1 µg/mL. Compounds 7c and 9c showed the most potent activity against MRSA (3167 and 3506) with a minimum inhibitory concentration (MIC) value of 1 µg/mL, which is equivalent to moxifloxacin and greater than gatifloxacin, oxacillin and norfloxacin. Additionally, compound 9c showed potent antibacterial activity against Bacillus subtilis (aerobic bacteria) with a MIC value of 2 µg/mL. CONCLUSION: The work suggests that these type of rhodanine compounds had a better potent activity against MRSA compared with other perviously reported rhodanine derivatives, which might provide a valuable information for the development of new antibacterial agents against multidrug-resistant clinical isolates MRSA.

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Background. Whether carotid tortuosity/kinking of the internal carotid artery leads to cerebral ischemia remains unclear. There is very little research about the hemodynamic variation induced by carotid tortuosity/kinking in the literature. The objective of this study was to research the blood pressure changes induced by carotid tortuosity/kinking. Methods. We first created a geometric model of carotid tortuosity/kinking. Based on hemodynamic boundary conditions, the hemodynamics of carotid tortuosity and kinking were studied via a finite element simulation. Then, an in vitro system was built to validate the numerical simulation results. The mean arterial pressure changes before and after carotid kinking were measured using pressure sensors in 12 patients with carotid kinking. Results. Numerical simulation revealed that the pressure drops increased with increases in the kinking angles. Clinical tests and in vitro experiments confirmed the numerical simulation results. Conclusions. Carotid kinking leads to blood pressure reduction. In certain conditions, kinking may affect the cerebral blood supply and be associated with cerebral ischemia.

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OBJECTIVE: To explore the feasibility, safety and efficacy of endovascular reconstructive treatment by multiple overlapping stents with or without coils. METHODS: Totally 17 patients of vertebrobasilar fusiform aneurysms treated by multiple overlapping stents with or without coils between September 2011 and September 2015 in Department of Neurosurgery, Beijing Hospital were retrospectively reviewed. There were 15 male and 2 female patients with mean age of (47±13) years. Clinical manifestations included subarachnoid hemorrhage in 5 patients, cerebral ischemia or infarction in the posterior circulation in 5 patients, mass effect accompanied with brainstem infarction in 1 patients, headache or dizziness in 4, and incidental findings in 2 patients. Aneurysm located in intracranial vertebral artery in 11 patients, vertebrobasilar junction in 2 patients, and basilar trunk in 4 patients. Mean aneurysmal size was 18.5 mm×8.0 mm(length×width). RESULTS: Sole stenting with overlapping stents was performed in 8 patients, and overlapping stents with coils was applied in 9 patients. Post-procedural hemorrhage occurred in a patient with a giant basilar trunk fusiform aneurysm and led to death. The 16 surviving patients were clinically followed up for a mean of 21.1 months. One patient had a modified Rankin score of 4, and the other patients had a good recovery. Among 15 patients with a mean angiographic follow-up of 8.6 months, 9 patients had their aneurysms further thrombosed, 3 patients were stable, and 3 patients with a recurred aneurysm. Final complete occlusion was achieved in 7 patients. CONCLUSION: Reconstructive treatment by overlapping stents with or without coils is feasible and relative safe in vertebrobasilar fusiform aneurysms.

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