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The inhibitory effects of cold plasma-activated water (PAW) on the formation of AGEs and methylimidazoles in cookies was examined. The results showed that different PAW (parameters: 50 W-50 s, 50 W-100 s, 50 W-150 s, 100 W-50 s, 100 W-100 s, and 100 W-150 s) reduced the contents of AGEs and methylimidazoles, in which the maximum inhibition rates were 47.38% and 40.17% for free and bound AGEs and 44.16% and 40.31% for free and bound methylimidazoles, respectively. Moreover, the mechanisms associated with the elimination of carbonyl intermediates and free radicals was determined by electron paramagnetic resonance (EPR) and high performance liquid chromatography-ultraviolet/visible absorption detector (HPLC-UV/Vis). The results showed the quenching of total free radicals, alkyl free radicals, and HO· by PAW, leading to the suppression of glyoxal and methylglyoxal intermediates. These findings support PAW as a promising agent to enhance the safety of cookies.
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The concurrent environmental contamination by nanoplastics (NPs) and norfloxacin (NOR) is a burgeoning concern, with significant accumulations in various ecosystems and potential ingress into the human body via the food chain, posing threats to both public health and ecological balance. Despite the gravity of the situation, studies on the co-exposure contamination effects of these substances are limited. Moreover, the response mechanisms of key functional proteins to these pollutants are yet to be fully elucidated. In this work, we conducted a comprehensive assessment of the interaction mechanisms of NPs and NOR with lysozyme under both single and co-exposure condition, utilizing dynamic light scattering, ζ-potential measurements, multi-spectroscopy methods, enzyme activity assays and molecular docking, to obtain a relationship between the compound effects of NPs and NOR. Our results indicate that NPs adsorb NOR on their surface, forming more stable aggregates. These aggregates influence the conformation, secondary structure (α-Helix ratio decreased by 3.1 %) and amino acid residue microenvironment of lysozyme. And changes in structure affect the activity of lysozyme (reduced by 39.9 %) with the influence of composited pollutants exerting stronger changes. Molecular simulation indicated the key residues Asp 52 for protein function located near the docking site, suggesting pollutants preferentially binds to the active center of lysozyme. Through this study, we have found the effect of increased toxicity on lysozyme under the compounded conditions of NPs and NOR, confirming that the increased molecular toxicity of NPs and NOR is predominantly realized through the increase in particle size and stability of the aggregates under weak interactions, as well as induction of protein structural looseness. This study proposes a molecular perspective on the differential effects and mechanisms of NPs-NOR composite pollution, providing new insights into the assessment of in vitro responses to composite pollutant exposure.
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Simulación del Acoplamiento Molecular , Muramidasa , Norfloxacino , Muramidasa/química , Norfloxacino/toxicidad , Contaminantes Ambientales/toxicidad , Nanopartículas/toxicidad , Antibacterianos/toxicidadRESUMEN
The early phases of clathrin mediated endocytosis are organized through a highly complex interaction network mediated by clathrin associated sorting proteins (CLASPs) that comprise long intrinsically disordered regions (IDRs). AP180 is a CLASP exclusively expressed in neurons and comprises a long IDR of around 600 residues, whose function remains partially elusive. Using NMR spectroscopy, we discovered an extended and strong interaction site within AP180 with the major adaptor protein AP2, and describe its binding dynamics at atomic resolution. We find that the 70 residue-long site determines the overall interaction between AP180 and AP2 in a dynamic equilibrium between its bound and unbound states, while weaker binding sites contribute to the overall affinity at much higher concentrations of AP2. Our data suggest that this particular interaction site might play a central role in recruitment of adaptors to the clathrin coated pit, whereas more transient and promiscuous interactions allow reshaping of the interaction network until cargo uptake inside a coated vesicle.
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Complejo 2 de Proteína Adaptadora , Clatrina , Endocitosis , Proteínas de Ensamble de Clatrina Monoméricas , Unión Proteica , Complejo 2 de Proteína Adaptadora/metabolismo , Clatrina/metabolismo , Sitios de Unión , Proteínas de Ensamble de Clatrina Monoméricas/metabolismo , Proteínas de Ensamble de Clatrina Monoméricas/genética , Humanos , Animales , Espectroscopía de Resonancia Magnética , Vesículas Cubiertas por Clatrina/metabolismo , Proteínas Intrínsecamente Desordenadas/metabolismo , Proteínas Intrínsecamente Desordenadas/química , Proteínas Intrínsecamente Desordenadas/genéticaRESUMEN
Exploiting a convenient and highly bioavailable ocular drug delivery approach is currently one of the hotspots in the pharmaceutical industry. Eyelid topical application is seen to be a valuable strategy in the treatment of chronic ocular diseases. To further elucidate the feasibility of eyelid topical administration as an alternative route for ocular drug delivery, pharmacokinetic and pharmacodynamic studies of pilocarpine were conducted in rabbits. Besides, a novel physiologically based pharmacokinetic (PBPK) model describing eyelid transdermal absorption and ocular disposition was developed in rabbits. The PBPK model of rabbits was extrapolated to human by integrating the drug-specific permeability parameters and human physiological parameters to predict ocular pharmacokinetic in human. After eyelid topical application of pilocarpine, the concentration of pilocarpine in iris peaked at 2 h with the value of 18,724 ng/g and the concentration in aqueous humor peaked at 1 h with the value of 1,363 ng/mL. Significant miotic effect were observed from 0.5 h to 4.5 h after eyelid topical application of pilocarpine in rabbits, while that were observed from 0.5 h to 3.5 h after eyedrop instillation. The proposed eyelid PBPK model was capable of reasonably predicting ocular exposure of pilocarpine after application on the eyelid skin and based on the PBPK model, the human ocular concentration was predicted to be 10-fold lower than that in rabbits. And it was suggested that drugs applied on the eyelid skin could transfer into the eyeball through corneal pathway and scleral pathway. This work could provide pharmacokinetic and pharmacodynamic data for the development of eyelid drug delivery, as well as the reference for clinical applications.
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Párpados , Modelos Biológicos , Pilocarpina , Pilocarpina/farmacocinética , Pilocarpina/administración & dosificación , Animales , Conejos , Humanos , Párpados/metabolismo , Párpados/efectos de los fármacos , Administración Tópica , Masculino , Mióticos/farmacocinética , Mióticos/administración & dosificación , Agonistas Muscarínicos/farmacocinética , Agonistas Muscarínicos/administración & dosificación , Humor Acuoso/metabolismo , Humor Acuoso/efectos de los fármacos , Administración Oftálmica , Absorción Cutánea/efectos de los fármacos , Soluciones Oftálmicas/farmacocinética , Soluciones Oftálmicas/administración & dosificación , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Septic cardiomyopathy is a severe cardiovascular disease with a poor prognosis. Previous studies have reported the involvement of ferroptosis in the pathogenesis of septic cardiomyopathy. SGLT2 inhibitors such as dapagliflozin have been demonstrated to improve ischemia-reperfusion injury by alleviating ferroptosis in cardiomyocyte. However, the role of dapagliflozin in sepsis remains unclear. Therefore, our study aims to investigate the therapeutic effects of dapagliflozin on LPS-induced septic cardiomyopathy. Our results indicate that dapagliflozin improved cardiac function in septic cardiomyopathy experimental mice. Mechanistically, dapagliflozin works by inhibiting the translation of key proteins involved in ferroptosis, such as GPX4, FTH1, and SLC7A11. It also reduces the transcription of lipid peroxidation-related mRNAs, including PTGS2 and ACSL4, as well as iron metabolism genes TFRC and HMOX1.
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Compuestos de Bencidrilo , Ferroptosis , Glucósidos , Lipopolisacáridos , Ferroptosis/efectos de los fármacos , Animales , Ratones , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/uso terapéutico , Glucósidos/farmacología , Glucósidos/uso terapéutico , Lipopolisacáridos/toxicidad , Masculino , Cardiomiopatías/tratamiento farmacológico , Ratones Endogámicos C57BL , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patologíaRESUMEN
In the autonomous navigation of mobile robots, precise positioning is crucial. In forest environments with weak satellite signals or in sites disturbed by complex environments, satellite positioning accuracy has difficulty in meeting the requirements of autonomous navigation positioning accuracy for robots. This article proposes a vision SLAM/UWB tightly coupled localization method and designs a UWB non-line-of-sight error identification method using the displacement increment of the visual odometer. It utilizes the displacement increment of visual output and UWB ranging information as measurement values and applies the extended Kalman filtering algorithm for data fusion. This study utilized the constructed experimental platform to collect images and ultra-wideband ranging data in outdoor environments and experimentally validated the combined positioning method. The experimental results show that the algorithm outperforms individual UWB or loosely coupled combination positioning methods in terms of positioning accuracy. It effectively eliminates non-line-of-sight errors in UWB, improving the accuracy and stability of the combined positioning system.
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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. Minichromosome maintenance proteins (MCMs), particularly MCM2-7, are upregulated in various cancers, including HCC. The aim of the present study was to investigate the role of MCM2-7 in human liver HCC (LIHC) and the regulation of the protein homeostasis of MCM6 by a specific E3 ligase. Bioinformatics analyses demonstrated that MCM2-7 were highly expressed in LIHC compared with corresponding normal tissues at the mRNA and protein levels, and patients with LIHC and high mRNA expression levels of MCM2, MCM3, MCM6 and MCM7 had poor overall survival rates. Cell Counting Kit-8 and colony formation assays revealed that the knockdown of MCM2, MCM3, MCM6 or MCM7 in Huh7 and Hep3B HCC cells inhibited cell proliferation and colony formation. In addition, pull-down, co-immunoprecipitation and ubiquitination assays demonstrated that RNF125 interacts with MCM6 and mediates its ubiquitination. Furthermore, co-transfection experiments indicated that RNF125 promoted the proliferation of HCC cells mainly through MCM6. In summary, the present study suggests that the RNF125-MCM6 axis plays an important role in the regulation of HCC cell proliferation and is a promising therapeutic target for the treatment of LIHC.
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OBJECTIVE: To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis. METHODS: The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network, Wipu, Wanfang, The Cochrane Library, Web of science and Pubmed, and statistical analysis was performed using RevMan 5.3 software. The rates of malrotation, rotational deformity, internal/external deformity, anterior/posterior deformity, non-union, infection, secondary surgery and operative time were compared between the fibula fixation and non-fixation groups. RESULTS: A total of 11 publications were included, six randomised controlled trials and five case-control trials, eight of which were of high quality. A total of 813 cases were included, of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22, 95%CI(0.10, 0.45), P<0.000 1] and internal/external deformity[RR=0.34, 95%CI(0.14, 0.84), P=0.02] and promoted fracture healing [RR=0.76, 95%CI(0.58, 0.99), P=0.04]. In contrast, the rates of poor reduction [RR=0.48, 95% CI(0.10, 2.33), P=0.36], anterior/posterior deformity[RR=1.50, 95%CI(0.76, 2.96), P=0.24], infection[RR=1.43, 95%CI(0.76, 2.72), P=0.27], secondary surgery[RR=1.32, 95%CI(0.82, 2.11), P=0.25], and operative time[MD=10.21, 95%CI(-17.79, 38.21), P=0.47] were not statistically significant (P>0.05) for comparison. CONCLUSION: Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.
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Peroné , Fracturas Óseas , Humanos , Peroné/cirugía , Fracturas Óseas/cirugía , Fracturas Óseas/complicaciones , Tibia/cirugía , Curación de Fractura , Fijación Interna de Fracturas , Resultado del TratamientoRESUMEN
Using unnatural amino acid mutagenesis, we made a mutant of CaMKII that forms a covalent linkage to Calmodulin upon illumination by UV light. Like wild-type CaMKII, the L308BzF mutant stoichiometrically binds to Calmodulin, in a calcium-dependent manner. Using this construct, we demonstrate that Calmodulin binding to CaMKII, even under these stochiometric conditions, does not perturb the CaMKII oligomeric state. Furthermore, we were able to achieve activation of CaMKII L308BzF by UV-induced binding of Calmodulin, which, once established, is further insensitive to calcium depletion. In addition to the canonical auto-inhibitory role of the regulatory segment, inter-subunit crosslinking in the absence of CaM indicates that kinase domains and regulatory segments are substantially mobile in basal conditions. Characterization of CaMKIIL308BzF in vitro, and its expression in mammalian cells, suggests it could be a promising candidate for control of CaMKII activity in mammalian cells with light.
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Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Calmodulina , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/química , Calmodulina/química , Aminoácidos/metabolismo , Calcio/metabolismo , Unión Proteica , Fosforilación , MamíferosRESUMEN
BACKGROUND: Enhancing the precision of drug-drug interaction (DDI) prediction is essential for improving drug safety and efficacy. The aim is to identify the most effective fraction metabolized by CY3A4 (fm) for improving DDI prediction using physiologically based pharmacokinetic (PBPK) models. RESEARCH DESIGN AND METHODS: The fm values were determined for 33 approved drugs using a human liver microsome for in vitro measurements and the ADMET Predictor software for in silico predictions. Subsequently, these fm values were integrated into PBPK models using the GastroPlus platform. The PBPK models, combined with a ketoconazole model, were utilized to predict AUCR (AUCcombo with ketoconazole/AUCdosing alone), and the accuracy of these predictions was evaluated by comparison with observed AUCR. RESULTS: The integration of in vitro fm method demonstrates superior performance compared to the in silico fm method and fm of 100% method. Under the Guest-limits criteria, the integration of in vitro fm achieves an accuracy of 76%, while the in silico fm and fm of 100% methods achieve accuracies of 67% and 58%, respectively. CONCLUSIONS: Our study highlights the importance of in vitro fm data to improve the accuracy of predicting DDIs and demonstrates the promising potential of in silico fm in predicting DDIs.
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Citocromo P-450 CYP3A , Cetoconazol , Humanos , Citocromo P-450 CYP3A/metabolismo , Cetoconazol/metabolismo , Modelos Biológicos , Interacciones Farmacológicas , Microsomas Hepáticos/metabolismo , Simulación por ComputadorRESUMEN
The dodecameric protein kinase CaMKII is expressed throughout the body. The alpha isoform is responsible for synaptic plasticity and participates in memory through its phosphorylation of synaptic proteins. Its elaborate subunit organization and propensity for autophosphorylation allow it to preserve neuronal plasticity across space and time. The prevailing hypothesis for the spread of CaMKII activity, involving shuffling of subunits between activated and naive holoenzymes, is broadly termed subunit exchange. In contrast to the expectations of previous work, we found little evidence for subunit exchange upon activation, and no effect of restraining subunits to their parent holoenzymes. Rather, mass photometry, crosslinking mass spectrometry, single molecule TIRF microscopy and biochemical assays identify inter-holoenzyme phosphorylation (IHP) as the mechanism for spreading phosphorylation. The transient, activity-dependent formation of groups of holoenzymes is well suited to the speed of neuronal activity. Our results place fundamental limits on the activation mechanism of this kinase.
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Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Plasticidad Neuronal , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Fosforilación , Transducción de Señal , Holoenzimas/metabolismoRESUMEN
Ensartinib (X-396) is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) indicated for the treatment of ALK-positive patients with locally advanced or metastatic non-small cell lung cancer. Although in vitro experiments and molecular docking suggested its potential as a cytochrome P450 inhibitor, no further investigation or clinical trials have been conducted to assess its drug-drug interaction (DDI) risk. In this study, we conducted a series of in vitro experiments to elucidate the inhibition mechanism of ensartinib. Furthermore, a physiologically-based pharmacokinetic (PBPK) model was developed based on in vitro, in silico, and in vivo parameters, verified using clinical data, and applied to predict the clinical DDI mediated by ensartinib. The in vitro incubation experiments suggested that ensartinib exhibited strong time-dependent inhibition. Simulation results from the PBPK model indicated a significant increase in the exposure of CYP3A substrates in the presence of ensartinib, with the maximal plasma concentration and area under the plasma concentration-time curve increasing up to 12-fold and 29-fold for sensitive substrates. Based on these findings, it is evident that co-administration of ensartinib and CYP3A substrates requires careful regulatory consideration. SIGNIFICANCE STATEMENT: Ensartinib was found to be a strong time-dependent inhibitor of CYP3A for the first time based on in vitro experiments, but there was no research conducted to estimate the risk of drug-drug interaction (DDI) of ensartinib in clinic. Therefore, the first ensartinib physiologically based pharmacokinetic model was developed and applied to predict various untested scenarios. The simulation result indicated that the exposure of CYP3A substrate increased significantly and urged the further clinical DDI study.
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BACKGROUND: Galectin-3 (Gal-3), the only chimeric ß-galactosides-binding lectin, consists of Gal-3N (N-terminal regulatory peptide) and Gal-3C (C-terminal carbohydrate-recognition domain). Interestingly, Gal-3C could specifically inhibit endogenous full-length Gal-3 to exhibit anti-tumor activity. Here, we aimed to further improve the anti-tumor activity of Gal-3C via developing novel fusion proteins. METHODS: PK5 (the fifth kringle domain of plasminogen) was introduced to the N-terminus of Gal-3C via rigid linker (RL) to generate novel fusion protein PK5-RL-Gal-3C. Then, we investigated the anti-tumor activity of PK5-RL-Gal-3C in vivo and in vitro by using several experiments, and figured out their molecular mechanisms in anti-angiogenesis and cytotoxicity to hepatocellular carcinoma (HCC). RESULTS: Our results show that PK5-RL-Gal-3C can inhibit HCC both in vivo and in vitro without obvious toxicity, and also significantly prolong the survival time of tumor-bearing mice. Mechanically, we find that PK5-RL-Gal-3C inhibits angiogenesis and show cytotoxicity to HCC. In detail, HUVEC-related and matrigel plug assays indicate that PK5-RL-Gal-3C plays an important role in inhibiting angiogenesis by regulating HIF1α/VEGF and Ang-2 both in vivo and in vitro. Moreover, PK5-RL-Gal-3C induces cell cycle arrest at G1 phase and apoptosis with inhibition of Cyclin D1, Cyclin D3, CDK4, and Bcl-2, but activation of p27, p21, caspase-3, -8 and -9. CONCLUSION: Novel fusion protein PK5-RL-Gal-3C is potent therapeutic agent by inhibiting tumor angiogenesis in HCC and potential antagonist of Gal-3, which provides new strategy for exploring novel antagonist of Gal-3 and promotes their application in clinical treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Fase G1 , Puntos de Control del Ciclo Celular , Apoptosis , Galectina 3 , Proliferación Celular , Línea Celular TumoralRESUMEN
Background: Peritoneal metastases (PMs) are the most frequent metastatic pattern with a very poor prognosis in stage IV gastric cancer (GC). An effective therapeutic option has yet to be established. Combination therapy of anti-angiogenesis therapy, immunotherapy and chemotherapy was first used in advanced GC for perioperative treatment in this case. Case Description: A 39-year-old man was diagnosed with stage IV GC with PM (CY1, P1) and the patient had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 and adequate organ function. After disease progression on the first-line chemotherapy of paclitaxel plus S-1, the patient received a transformational therapy of camrelizumab (immune checkpoint inhibitors) plus apatinib (anti-angiogenic agent) combined with chemotherapy leading to macroscopic disappearance of the peritoneal lesions, negative peritoneal cytology, and the absence of other distant metastases, rendering him suitable to accept a radical gastrectomy with D2 lymph node dissection. The postoperative histopathology showed a tumor regression rate of more than 90%. Later, the patient was admitted for adjuvant therapy of camrelizumab plus apatinib combined with chemotherapy and relapsed at around 8 months after surgery. Treatment was well tolerated with no significant adverse effects. Conclusions: Camrelizumab plus apatinib combined with chemotherapy as second-line treatment demonstrated feasible anti-tumor activity and manageable safety in this advanced GC patient with PM and provided an opportunity for radical resection, improving the objective response rate (ORR) and prolonging patient survival. The incorporation may overcome resistance to treatment with therapy alone and produce synergistic effects, indicating a promising treatment option in the clinic to GC with PM.
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OBJECTIVE: To explore the technique of autogenous bone graft combined with plate fixation in total knee arthroplasty(TKA) with severe proximal medial tibial bone defect. METHODS: From March 2012 to October 2018, 21 patients (9 males and 12 females) with severe bone defects in the proximal medial tibia during primary total knee arthroplasty were treated with autogenous structural bone grafting and steel plate fixation, with an age of 61 to 77 years old with an average of (69.6±9.1) years and a course of 64 to 257 months with an average of (73.6±170.7) months. According to Rand classification, there were 13 cases of type â ¢b and 8 cases of type â £b. Postoperative complications were observed, and knee joint function was evaluated by the Hospital for Special Surgery (HSS) score and SF-36 quality of life score. RESULTS: All 21 patients were followed up for 37 to 64 months with an average of (49.5±13.7) months. The incisions of all patients healed smoothly, and 2 patients developed lower limb intermuscular venous plexus thrombosis after operation. There were no periprosthetic infection, loosening of prosthesis and other complications. The autogenous bone grafts of all patients achieved bony healing during postoperative X-ray follow-up, and the healing time was 8 to 13 months with an average of (10.1±2.3) months. The HSS score of patients increased significantly from 30 to 48 with an average of (53.4±4.2) before operation to 75 to 92 with an average of (81.2±8.4) at the final follow-up (P<0.05). The SF-36 quality of life score of patients after operation was significantly different from that before operation (P<0.05). CONCLUSION: The technique of autogenous bone graft combined with steel plate fixation can achieve satisfactory osseointegration effect in the treatment of severe proximal tibial bone defects in primary knee arthroplasty, with less complications and obvious improvement in knee function.
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Artroplastia de Reemplazo de Rodilla , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Artroplastia de Reemplazo de Rodilla/métodos , Tibia/trasplante , Trasplante Óseo/métodos , Calidad de Vida , Trasplante Autólogo , AceroRESUMEN
Cross-linking mass spectrometry (XL-MS) is an attractive method for the proteome-wide characterization of protein structures and interactions. Currently, the depth of inâ vivo XL-MS studies is lagging behind the established applications to cell lysates, because cross-linking reagents that can penetrate intact cells and strategies to enrich cross-linked peptides lack efficiency. To tackle these limitations, we have developed a phosphonate-containing cross-linker, tBu-PhoX, that efficiently permeates various biological membranes and can be robustly enriched using routine immobilized metal ion affinity chromatography. We have established a tBu-PhoX-based inâ vivo XL-MS approach that enables cross-links in intact human cells to be identified in high numbers with substantially reduced analysis time. Collectively, the developed cross-linker and XL-MS approach pave the way for the comprehensive XL-MS characterization of living systems.
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Proteoma , Cromatografía de Afinidad , Reactivos de Enlaces Cruzados/química , Humanos , Imidazoles , Espectrometría de Masas/métodosRESUMEN
An increasing number of cybercrimes has presented new global challenges to law enforcement agencies that traditionally operate within designated geographical jurisdictions and patrol territories. The borderless nature of cyberspace has brought substantial opportunities-both legal and illegal-to its users, and many local law enforcement agencies have encountered motivated offenders taking advantage of the globally connected Internet and causing damage locally and transnationally. This study examines a high-profile case of European criminals who hacked into a Taiwanese financial institution-First Commercial Bank (FCB)-and programmed its ATMs to "spit out" cash netting the thieves $2.6 million US dollars in 2016 summer. Before the incident of FCB, this European criminal group committed more than a hundred similar ATMs hackings, victimizing dozens of financial institutions across several European countries, and profiting over one billion Euros. FCB is the only case revealing specific details about the modus operandi of ATM hacking thus far, in addition to disclosing reactions from law enforcement. By analyzing qualitative data collected from different branches of law enforcement involved in the investigations, this unique case study underscores the importance of national-local law enforcement collaboration in fighting transnational cybercrime. Empirical implications are particularly valuable in the law enforcement context of "turf jealousies" when defending homeland security.
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Criminales , Internet , Aplicación de la Ley , Pueblo Asiatico , Europa (Continente) , HumanosRESUMEN
Alopecines A-E (1-5), five unusual matrine-type alkaloids featuring with an additional dichlorocyclopropane (1-3) or a di/tri-chloromethyl (4/5) attached on the D ring, were isolated from the seeds of Sophora alopecuroides. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques, and X-ray diffraction analyses or time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Alkaloid 4 exhibited potent inhibitory effects on the proliferation of ConA-induced T lymphocytes or LPS-induced B cells with IC50 value of 3.98 or 3.74 µM, respectively.