Cycloplatinated (II) Complex Based on Isoquinoline Alkaloid Elicits Ferritinophagy-Dependent Ferroptosis in Triple-Negative Breast Cancer Cells.

The development and optimization of metal-based anticancer drugs with novel cytotoxic mechanisms have emerged as key strategies to overcome chemotherapeutic resistance and side effects. Agents that simultaneously induce ferroptosis and autophagic death have received extensive attention as potential modalities for cancer therapy. However, only a limited set of drugs or treatment modalities can synergistically induce ferroptosis and autophagic tumor cell death. In this work, we designed and synthesized four new cycloplatinated (II) complexes harboring an isoquinoline alkaloid C∧N ligand. On screening the in vitro activity of these agents, we found that Pt-3 exhibited greater selectivity of cytotoxicity, decreased resistance factors, and improved anticancer activity compared to cisplatin. Furthermore, Pt-3, which we demonstrate can initiate potent ferritinophagy-dependent ferroptosis, exhibits less toxic and better therapeutic activity than cisplatin in vivo. Our results identify Pt-3 as a promising candidate or paradigm for further drug development in cancer treatment.

Tandem Photocatalysis of CO2 to C2H4 via a Synergistic Rhenium-(I) Bipyridine/Copper-Porphyrinic Triazine Framework.

The photocatalytic conversion of CO2 into C2+ products such as ethylene is a promising path toward the carbon neutral goal but remains a big challenge due to the high activation barrier for CO2 and similar reduction potentials of many possible multi-electron-transfer products. Herein, an effective tandem photocatalysis strategy has been developed to support conversion of CO2 to ethylene by construction of the synergistic dual sites in rhenium-(I) bipyridine fac-[ReI(bpy)(CO)3Cl] (Re-bpy) and copper-porphyrinic triazine framework [PTF(Cu)]. With these two catalysts, a large amount of ethylene can be produced at a rate of 73.2 µmol g-1 h-1 under visible light irradiation. However, ethylene cannot be obtained from CO2 by use of either component of the Re-bpy or PTF(Cu) catalysts alone; with a single catalyst, only monocarbon product CO is produced under similar conditions. In the tandem photocatalytic system, the CO generated at the Re-bpy sites is adsorbed by the nearby Cu single sites in PTF(Cu), and this is followed by a synergistic C-C coupling process which ultimately produces ethylene. Density functional theory calculations demonstrate that the coupling process between PTF(Cu)-*CO and Re-bpy-*CO to form the key intermediate Re-bpy-*CO-*CO-PTF(Cu) is vital to the C2H4 production. This work provides a new pathway for the design of efficient photocatalysts for photoconversion of CO2 to C2 products via a tandem process driven by visible light under mild conditions.

Cobalt-Based Metal-Organic Cages for Visible-Light-Driven Water Oxidation.

Water oxidation to molecular oxygen is indispensable but a challenge for splitting H2O. In this work, a series of Co-based metal-organic cages (MOCs) for photoinduced water oxidation were prepared. MOC-1 with both bis(µ-oxo) bridged dicobalt and Co-O (O from H2O) displays catalytic activity with an initial oxygen evolution rate of 80.4 mmol/g/h and a TOF of 7.49 × 10-3 s-1 in 10 min. In contrast, MOC-2 containing only Co-O (O from H2O) in the structure results in a lower oxygen evolution rate (40.8 mmol/g/h, 4.78 × 10-3 s-1), while the amount of oxygen evolved from the solution of MOC-4 without both active sites is undetectable. Isotope experiments with or without H218O as the reactant successfully demonstrate that the molecular oxygen was produced from water oxidation. Photophysical and electrochemical studies reveal that photoinduced water oxidation initializes via electron transfer from the excited [Ru(bpy)3]2+* to Na2S2O8, and then, the cobalt active sites further donate electrons to the oxidized [Ru(bpy)3]3+ to drive water oxidation. This proof-of-concept study indicates that MOCs can work as potential efficient catalysts for photoinduced water oxidation.

Bacterial community in saline farmland soil on the Tibetan plateau: responding to salinization while resisting extreme environments.

BACKGROUND: Salinization damages the health of soil systems and reduces crop yields. Responses of microbial communities to salinized soils and their functional maintenance under high salt stress are valuable scientific problems. Meanwhile, the microbial community of the salinized soil in the plateau environment is less understood. Here, we applied metagenomics technology to reveal the structure and function of microorganisms in salinized soil of the Tibetan Plateau. RESULTS: The diversity of composition and function of microbial community in saline soil have changed significantly. The abundances of chemoautotrophic and acidophilic bacteria comprising Rhodanobacter, Acidobacterium, Candidatus Nitrosotalea, and Candidatus Koribacter were significantly higher in saline soil. The potential degradation of organic carbon in the saline soil, as well as the production of NO and N2O via denitrification, and the production of sulfate by sulfur oxidation were significantly higher than the non-saline soil. Both types of soils were rich in genes encoding resistance to environmental stresses (i.e., cold, ultraviolet light, and hypoxia in Tibetan Plateau). The resistance of the soil microbial communities to the saline environment is based on the absorption of K+ as the main mechanism, with cross-protection proteins and absorption buffer molecules as auxiliary mechanisms in our study area. Network analysis showed that functional group comprising chemoautotrophic and acidophilic bacteria had significant positive correlations with electrical conductivity and total sulfur, and significant negative correlations with the total organic carbon, pH, and available nitrogen. The soil moisture, pH, and electrical conductivity are likely to affect the bacterial carbon, nitrogen, and sulfur cycles. CONCLUSIONS: These results indicate that the specific environment of the Tibetan Plateau and salinization jointly shape the structure and function of the soil bacterial community, and that the bacterial communities respond to complex and harsh living conditions. In addition, environmental feedback probably exacerbates greenhouse gas emissions and accelerates the reduction in the soil pH. This study will provide insights into the microbial responses to soil salinization and the potential ecological risks in the special plateau environment.

Neuroprotective Effect of Fructus broussonetiae on APP/PS1 Mice via Upregulation of AKT/ß-Catenin Signaling.

OBJECTIVE: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD). METHODS: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice. To further explore the mechanisms underlying FB's protective effect, PC-12 cells were treated with Aß25-35 in order to establish an in vitro model of AD. RESULTS: FB-treated mice showed improved learning and memory capacity on both the Morris water maze and object recognition tests. RNA-seq of hippocampal tissue from APP/PS1 mice showed that FB had effects on multiple signaling pathways, specifically decreasing cell apoptotic signaling and increasing AKT and ß-catenin signaling. Similarly, FB up-regulated both AKT and ß-catenin signaling in PC-12 cells pre-treated with Aß25-35, in which AKT positively regulated ß-catenin signaling. Further study showed that AKT promoted ß-catenin signaling via enhancing ß-catenin (Ser552) phosphorylation. Moreover, AKT and ß-catenin signaling inhibition both resulted in the attenuated survival of FB-treated cells, indicating the AKT/ß-catenin signaling is a crucial mediator in FB promoted cell survival. CONCLUSIONS: FB exerted neuroprotective effects on hippocampal cells of APP/PS1 mice, as well as improved cell viability in an in vitro model of AD. The protective actions of FB occurred via the upregulation of AKT/ß-catenin signaling.

Facile Top-Down Strategy for Direct Metal Atomization and Coordination Achieving a High Turnover Number in CO2 Photoreduction.

Developing unique single atoms as active sites is vitally important to boosting the efficiency of photocatalytic CO2 reduction, but directly atomizing metal particles and simultaneously adjusting the configuration of individual atoms remain challenging. Herein, we demonstrate a facile strategy at a relatively low temperature (500 °C) to access the in situ metal atomization and coordination adjustment via the thermo-driven gaseous acid. Using this strategy, the pyrolytic gaseous acid (HCl) from NH4Cl could downsize the large metal particles into corresponding ions, which subsequently anchored onto the surface defects of a nitrogen-rich carbon (NC) matrix. Additionally, the low-temperature treatment-induced C═O motifs within the interlayer of NC could bond with the discrete Fe sites in a perpendicular direction and finally create stabilized Fe-N4O species with high valence status (Fe3+) on the shallow surface of the NC matrix. It was found that the Fe-N4O species can achieve a highly efficient CO2 conversion when accepting energetic electrons from both homogeneous and heterogeneous photocatalysts. The optimized sample achieves a maximum turnover number (TON) of 1494 within 1 h in CO generation with a high selectivity of 86.7% as well as excellent stability. Experimental and theoretical results unravel that high valence Fe sites in Fe-N4O species can promote the adsorption of CO2 and lower the formation barrier of key intermediate COOH* compared with the traditional Fe-N4 moiety with lower chemical valence. Our discovery provides new points of view in the construction of more efficient single-atom cocatalysts by considering the optimization of the atomic configuration for high-performance CO2 photoreduction.

Accelerating Streamline Tracking in Groundwater Flow Modeling on GPUs.

Streamline simulation in groundwater flow modeling is a time-consuming process when a large number of streamlines are analyzed. We develop a parallelization method on graphics processing units (GPUs) for the semi-analytical particle tracking algorithm developed by Pollock (1988). Compute Unified Device Architecture was used to implement the parallel method. Forward and backward tracking of a streamline is handled by an individual thread. A GPU includes a grid of blocks where a block handles 32 threads. We use multi-GPUs to accelerate streamline tracking in a flow model with millions of particles. The method was examined to simulate streamlines for identifying three-dimensional (3D) flow systems in a Tóthian basin. The speedup exceeds 1000 when 8 NVIDIA GPUs are used to simulate 5 million or more streamlines.

Upregulation of aryl hydrocarbon receptor nuclear translocator 2 in the hippocampi of post-stroke depression rats.

Aryl hydrocarbon receptor nuclear translocator protein 2 (ARNT2), a member of the basic helix-loop-helix superfamily of transcription factors, may serve a vital role in neuronal survival and cell proliferation via formation of heterodimers with hypoxia-inducible factor-1α. Previous studies indicated that ARNT2 levels were elevated in the brains of ischemic rats; however, the involvement of ARNT2 in post-stroke depression (PSD) rats is not well understood. Therefore, the present study aimed to investigate the levels of ARNT2 in the hippocampi of PSD rats, and to clarify the potential association between ARNT2 and behavioral performance. A PSD rat model was established by middle cerebral artery occlusion (MCAO) followed by a 4-week chronic unpredictable mild stress (CUMS) regimen. A sucrose preference test and open field test (OFT) were conducted, and body weight was measured. In addition, reverse transcription-polymerase chain reaction and immunohistochemistry were performed to measure ARNT expression. Results indicated that MCAO+CUMS rats had lower weight gain, consumed less sucrose and moved less compared with controls. Furthermore, the mRNA and protein levels of ARNT in MCAO+CUMS rats were increased compared with in controls. The sucrose preference index and horizontal movement distance in the OFT were positively correlated with ARNT mRNA level. Thus, from these findings it was suggested that ARNT2 may be positively associated with improvement of cognitive impairment, and therefore may be a potential target in PSD treatment.

Defective Pt nanoparticles encapsulated in mesoporous metal-organic frameworks for enhanced catalysis.

Highly dispersed ultrafine defective Pt nanoparticles (NPs) encapsulated in the mesopores of MIL-101 were successfully achieved for the first time through a facile chemical dealloying approach. PtCo alloy NPs inside the mesoporous MIL-101 were firstly formed via a double-solvent method and the Co species were subsequently selectively etched by diluted nitric acid to achieve the defective Pt NPs. Compared with PtCo alloy NPs, the as-prepared defective Pt NPs showed an improved catalytic activity towards the hydrogenation of nitroarenes under mild conditions.

Highly selective sensing of Fe3+ by an anionic metal-organic framework containing uncoordinated nitrogen and carboxylate oxygen sites.

Fast and highly selective detection of trace amounts of metal ions has become one of the most urgent issues concerning public security and living systems. However, developing a highly efficient fluorescent sensor for metal ions still remains a great challenge. Metal-organic frameworks (MOFs) are a promising class of porous fluorescent sensors towards ion detection. Herein, the anionic MOF FJI-C8 based on the π-conjugated aromatic ligand H6TDPAT (2,4,6-tris(3,5-dicarboxylphenylamino)-1,3,5-triazine) containing uncoordinated nitrogen and carboxylate oxygen atoms was chosen as highly efficient sensor for selective detection of Fe3+. Due to the strong interaction between Fe3+ and Lewis base sites (uncoordinated nitrogen and carboxylate oxygen atoms), the high overlap between the emission spectrum of the anionic FJI-C8 and the absorption spectrum of Fe3+, and the good overlap of the excitation spectrum of the host material FJI-C8 with the absorption spectrum of Fe3+, FJI-C8 exhibited a high sensitivity (0.0233 mM of Fe3+) and extra selectivity (Ksv = 8245 M-1) for the rapid detection (less than 30 s) of Fe3+ with low usage (0.04 mg mL-1 of FJI-C8 suspension). To the best of our knowledge, this is the first example of a luminescent MOF chemosensor based on a trefoil ligand with the highest density of uncoordinated N and carboxylate O atoms for the highly selective detection of Fe3+. It is also crucial to note that this is a first time detection of Fe3+ using both FJI-C8 suspension and solid after filtration, and the results indicate that the detection of Fe3+ using the FJI-C8 suspension is better. This study will pave the way for designing luminescent MOF chemosensors for the detection of Fe3+ ion.

Conventional Acupuncture for Cardiac Arrhythmia: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: To exam the effect and safety of conventional acupuncture (CA) on cardiac arrhythmia. METHODS: Nine medical databases were searched until February 2016 for randomized controlled trials. Heterogeneity was measured by Cochran Q test. Meta-analysis was conducted if I2 was less than 85% and the characteristics of included trials were similar. RESULTS: Nine qualified studies involving 638 patients were included. Only 1 study had definitely low risk of bias, while 7 trials were rated as unclear and 1 as high. Meta-analysis of CA alone did not have a significant benefit on response rate compared to amiodarone in patients with atrial fibrillation (Af) and atrial flutter (AF) [relative risk (RR): 1.09; 95% confidence interval (CI): 0.79-1.49; P=0.61; I2=61%, P=0.11]. However, 1 study with higher methodological quality detected a lower recurrence rate of Af in CA alone as compared with sham acupuncture plus no treatment, and benefits on ventricular rate and time of conversion to normal sinus rhythm were found in CA alone group by 1 study, as well as the response rate in CA plus deslanoside group by another study. Meta-analysis of CA plus anti-arrhythmia drug (AAD) was associated with a significant benefit on the response rate when compared with AAD alone in ventricular premature beat (VPB) patients (RR, 1.19, 95% CI: 1.05-1.34; P=0.005; I2=13%, P=0.32), and an improvement in quality-of-life score (QOLS) of VPB also showed in 1 individual study. Besides, a lower heart rate was detected in the CA alone group by 1 individual study when compared with no treatment in sinus tachycardia patients (MD-21.84 [-27.21,-16.47]) and lower adverse events of CA alone were reported than amiodarone. CONCLUSIONS: CA may be a useful and safe alternative or additive approach to AADs for cardiac arrhythmia, especially in VPB and Af patients, which mainly based on a pooled estimate and result from 1 study with higher methodological quality. However, we could not reach a robust conclusion due to low quality of overall evidence.

Fast, highly selective and sensitive anionic metal-organic framework with nitrogen-rich sites fluorescent chemosensor for nitro explosives detection.

Developing a highly efficient fluorescent sensor for detection of trace amounts of nitro explosives remains a great challenge. Porous metal-organic frameworks (MOFs) are one class of promising fluorescent sensors towards small molecules. Herein, we constructed an anionic Zn-based MOF FJI-C8 based on π-conjugated aromatic ligand H6TDPAT (2,4,6-tris(3,5-dicarboxylphenylamino)-1,3,5-triazine) containing nitrogen-rich sites. On account of the high density of uncoordinated N atoms, the high overlap between the emission spectrum of the anionic MOF FJI-C8 and the UV-vis absorption spectrum of the representative nitro explosive 2,4-dinitrophenol (2,4-DNP), and the porosity of the MOF, FJI-C8 is demonstrated to be an excellent chemosensor for 2,4-DNP with fast response time (less than 30s), high selectivity (Ksv=5.11×104M-1 for 2,4-DNP), extra sensitivity (LOD=0.002866mM for 2,4-DNP), low usage amount (0.04mg/mL), good stability and quantitative detection features. To the best of our knowledge, this is the first example for highly selective detection of 2,4-DNP. More importantly, theoretical calculation and control experiments unveiled that the energy transfer is the main mechanism for highly detection of 2,4-DNP. This work will pave the way for designing highly efficient luminescent chemosensors.

An imidazolium-functionalized mesoporous cationic metal-organic framework for cooperative CO2 fixation into cyclic carbonate.

A mesoporous cationic Cr-MOF, termed FJI-C10, containing imidazolium moieties, Lewis acidic Cr3+ sites and free halogens is constructed for the first time by a topology-guided one-pot synthesis. FJI-C10 exhibits excellent performances in CO2 adsorption (20.2 wt% at 273 K and 1 bar) and chemical fixation of CO2 into cyclic carbonates without the use of co-catalyst under atmospheric pressure.

Neuroprotective effect of the Chinese medicine Tiantai No. 1 and its molecular mechanism in the senescence-accelerated mouse prone 8.

Tiantai No. 1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No. 1 intragastrically to senescence-accelerated mouse prone 8 (SAMP8) mice (a model of Alzheimer's disease) at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer's disease-related proteins in the brain. Tiantai No. 1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No. 1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No. 1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No. 1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No. 1 is neuroprotective in the SAMP8 mouse model of Alzheimer's disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.

Postsynthetic ionization of an imidazole-containing metal-organic framework for the cycloaddition of carbon dioxide and epoxides.

A bifunctional imidazolium functionalized zirconium metal-organic framework (Zr-MOF), (I-)Meim-UiO-66 (2), was successfully prepared from the imidazole-containing Zr-MOF Im-UiO-66 (1) by a post-synthetic modification (PSM) method. It was found that the crystal size and pore features of the imidazole-containing 1 could be tuned at the nanoscale. The bifunctional MOF 2, containing Brønsted acid sites and iodide ions, was shown to be an efficient and recyclable heterogeneous catalyst for the cycloaddition of carbon dioxide (CO2) with epoxides, without the use of any co-catalyst, at ambient pressure. The solvent-free synthesis of the cyclic carbonate from CO2 and an epoxide was monitored by in situ Fourier transform infrared spectroscopy (FT-IR) and an acid/base synergistic catalysis mechanism was proposed. We hope that our strategy provides an effective approach for the introduction of functional N-heterocyclic groups into MOFs for potential applications.

Multifunctional metal-organic framework catalysts: synergistic catalysis and tandem reactions.

Metal-organic frameworks (MOFs) are porous crystalline materials constructed from metal ions or clusters and multidentate organic ligands. Recently, the use of MOFs or MOF composites as catalysts for synergistic catalysis and tandem reactions has attracted increasing attention due to their tunable open metal centres, functional organic linkers, and active guest species in their pores. In this review, the applications of MOFs with multiple active sites in synergistic organic catalysis, photocatalysis and tandem reactions are discussed. These multifunctional MOFs can be categorized by the type of active centre as follows: (i) open metal centres and functional organic linkers in the MOF structure, (ii) active guest sites in the pores and active sites in the MOF structure, and (iii) bimetallic nanoparticles (NPs) on MOF supports. The types of synergistic catalysis and tandem reactions promoted by multifunctional MOFs and their proposed mechanisms are presented in detail. Here, catalytic MOFs with a single type of active site and MOFs that only serve as supports to enhance substrate adsorption are not discussed.

Patterned growth of luminescent metal-organic framework films: a versatile electrochemically-assisted microwave deposition method.

Electrochemically-assisted microwave deposition technology, a facile method for the fabrication of luminescent metal-organic framework (LMOF) films, is presented herein. This method was further developed into a versatile method for preparing patterned LMOF films. The strategy based on this method can spatially locate microcrystals of MOFs on a surface, which provides great promise in anti-counterfeiting barcode applications.

An Anion Metal-Organic Framework with Lewis Basic Sites-Rich toward Charge-Exclusive Cationic Dyes Separation and Size-Selective Catalytic Reaction.

Organic dye pollutants become a big headache due to their toxic nature to the environment, and it should be one of the best solutions if we can separate and reuse them. Here, we report the synthesis and characterization of a microporous anion metal-organic framework (MOF) with Lewis basic sites-rich based on TDPAT (2,4,6-tris(3,5-dicarboxylphenylamino)-1,3,5-triazine) ligand, FJI-C2, which shows high adsorption and separation of cationic dye based on the charge-exclusive effect. Compared to other MOF materials, FJI-C2 shows the largest adsorption amount of methylene blue (1323 mg/g) at room temperature due to the nature of the anion frameworks and high surface area/pore volume. Furthermore, motivated by the adsorption properties of large guest molecules, we proceeded to investigate the catalytic behaviors of FJI-C2, not only because the large pore facilitates the mass transfer of guest molecules but also because the high density of Lewis basic sites can act as effective catalytic sites. As expected, FJI-C2 exhibits excellent catalytic performance for size-selective Knoevenagel condensation under mild conditions and can be reused several times without a significant decrease of the activity.

Microwave-assisted large scale synthesis of lanthanide metal-organic frameworks (Ln-MOFs), having a preferred conformation and photoluminescence properties.

Preparation of MOF on a large scale is a great challenge due to difficulties in reproducibility. A microwave synthesis procedure plays a major role in solving this problem. Moreover, achievement of the preferred conformation in the case of the flexible ligand is also an important factor as it affects the stability of the MOF. In this regard, lanthanides are suitable candidates due to their large size and coordination capabilities. A series of isostructural microporous lanthanide metal-organic frameworks (Ln-MOFs), formulated as [Ln (TTTPC)(NO2)2(Cl)]·(H2O)10 {Ln = La (1), Ce (2), Pr (3), Nd (4), Eu (5), Tb (6), Dy (7), Ho (8), Yb (9); H3TTTPC = 1,1',1''-tris(2,4,6-trimethylbenzene-1,3,5-triyl)-tris(methylene)-tris(pyridine-4-carboxylic acid)}, has been synthesized on a large scale via a microwave-assisted solvothermal reaction over 5 min. Otherwise, if a conventional solvothermal reaction is carried out at the same temperature, a much longer reaction time (2 days) and slow evaporation (5 days) are needed to produce the same compound in similar yield. Moreover, in these circumstances, conventional methods are useful only for small scale (10 mg) syntheses, but on using microwave-assisted synthesis, up to 2 g was obtained. Structural analysis reveals that the framework of the as-synthesized MOFs is a 6-connected network with point symbol (4(11)·6(4)), which is a subnet of a uninodal net having a new topology, sqc885. Thermal gravimetric analyses performed on as-synthesized MOFs reveal that the frameworks have moderate thermal stability. Gas sorption properties of 1 and 8 were studied by experimentally measuring nitrogen and hydrogen sorption isotherms. The luminescent properties of 5 and 6 were investigated and show characteristic emissions for Eu(3+) and Tb(3+) at room temperature.

Numerical modeling of slug tests with MODFLOW using equivalent well blocks.

Slug tests are a widely used technique to estimate aquifer hydraulic parameters and the test data are generally interpreted with analytical solutions under various assumptions. However, these solutions are not convenient when slug tests are required to be analyzed in a three-dimensional model for complex aquifer-aquitard systems. In this study, equivalent well blocks (EWB) are proposed in numerical modeling of slug test data with MODFLOW. Multi-well slug tests in partially penetrating wells with skin zones can be simulated. Accuracy of the numerical method is demonstrated by benchmarking with analytical solutions. The EWB method is applied in a case study on slug tests in aquitards in the Pearl River Delta, China.