Magneto-transport in the monolayer MoS2material system for high-performance field-effect transistor applications.

Electronic transport in monolayer MoS2is significantly constrained by several extrinsic factors despite showing good prospects as a transistor channel material. Our paper aims to unveil the underlying mechanisms of the electrical and magneto-transport in monolayer MoS2. In order to quantitatively interpret the magneto-transport behavior of monolayer MoS2on different substrate materials, identify the underlying bottlenecks, and provide guidelines for subsequent improvements, we present a deep analysis of the magneto-transport properties in the diffusive limit. Our calculations are performed on suspended monolayer MoS2and MoS2on different substrate materials taking into account remote impurity and the intrinsic and extrinsic phonon scattering mechanisms. We calculate the crucial transport parameters such as the Hall mobility, the conductivity tensor elements, the Hall factor, and the magnetoresistance over a wide range of temperatures, carrier concentrations, and magnetic fields. The Hall factor being a key quantity for calculating the carrier concentration and drift mobility, we show that for suspended monolayer MoS2at room temperature, the Hall factor value is around 1.43 for magnetic fields ranging from 0.001 to 1 Tesla, which deviates significantly from the usual value of unity. In contrast, the Hall factor for various substrates approaches the ideal value of unity and remains stable in response to the magnetic field and temperature. We also show that the MoS2over an Al2O3substrate is a good choice for the Hall effect detector. Moreover, the magnetoresistance increases with an increase in magnetic field strength for smaller magnetic fields before reaching saturation at higher magnetic fields. The presented theoretical model quantitatively captures the scaling of mobility and various magnetoresistance coefficients with temperature, carrier densities, and magnetic fields.

Beyond metals: theoretical discovery of semiconducting MAX phases and their potential application in thermoelectrics.

MAX phase is a family of ceramic compounds, typically known for their metallic properties. However, we show here that some of them may be narrow bandgap semiconductors. Using a series of first-principles calculations, we have investigated the electronic structures of 861 dynamically stable MAX phases. Notably, Sc2SC, Y2SC, Y2SeC, Sc3AuC2, and Y3AuC2 have been identified as semiconductors with band gaps ranging from 0.2 to 0.5 eV. Furthermore, we have assessed the thermodynamic stability of these systems by generating ternary phase diagrams utilizing evolutionary algorithm techniques. Their dynamic stabilities are confirmed by phonon calculations. Additionally, we have explored the potential thermoelectric efficiencies of these materials by combining Boltzmann transport theory with first-principles calculations. The relaxation times are estimated using scattering theory. The zT coefficients for the aforementioned systems fall within the range of 0.5 to 2.5 at temperatures spanning from 300 to 700 K, indicating their suitability for high-temperature thermoelectric applications.

Notch signaling regulates mineralization via microRNA modulation in dental pulp stem cells.

OBJECTIVES: This study investigated the miRNA expression profile in Notch-activated human dental stem pulp stem cells (DPSCs) and validated the functions of miRNAs in modulating the odonto/osteogenic properties of DPSCs. METHODS: DPSCs were treated with indirect immobilized Jagged1. The miRNA expression profile was examined using NanoString analysis. Bioinformatic analysis was performed, and miRNA expression was validated. Odonto/osteogenic differentiation was examined using alkaline phosphatase staining, Alizarin Red S staining, as well as odonto/osteogenic-related gene and protein expression. RESULTS: Fourteen miRNAs were differentially expressed in Jagged1-treated DPSCs. Pathway analysis revealed that altered miRNAs were associated with TGF-ß, Hippo, ErbB signalling pathways, FoxO and Ras signalling. Target prediction analysis demonstrated that 7604 genes were predicted to be targets for these altered miRNAs. Enrichment analysis revealed relationships to various DNA bindings. Among differentially expressed miRNA, miR-296-3p and miR-450b-5p were upregulated under Jagged1-treated conditions. Overexpression of miR-296-3p and miR-450b-5p enhanced mineralization and upregulation of odonto/osteogenic-related genes, whereas inhibition of these miRNAs revealed opposing results. The miR-296-3p and miR-450b-5p inhibitors attenuated the effects of Jagged1-induced mineralization in DPSCs. CONCLUSIONS: Jagged-1 promotes mineralization in DPSCs that are partially regulated by miRNA. The novel understanding of these miRNAs could lead to innovative controlled mechanisms that can be applied to modulate biology-targeted dental materials.

Computational design of novel MAX phase alloys as potential hydrogen storage media combining first principles and cluster expansion methods.

Finding a suitable material for hydrogen storage under ambient atmospheric conditions is challenging for material scientists and chemists. In this work, using a first principles based cluster expansion approach, the hydrogen storage capacity of the Ti2AC (A = Al, Ti, Cr, Mn, Fe, Co, Ni, Cu, and Zn) MAX phase and its alloys was studied. We found that hydrogen is energetically stable in Ti-A layers in which the tetrahedral site consisting of one A atom and three Ti atoms is energetically more favorable for hydrogen adsorption than other sites in the Ti-A layer. Ti2CuC has the highest hydrogen adsorption energy than other Ti2AC phases. We find that the 83.33% Cu doped Ti2AlxCu1-xC alloy structure is both energetically and dynamically stable and can store 3.66 wt% hydrogen under ambient atmospheric conditions, which is higher than that stored by both Ti2AlC and Ti2CuC phases. These findings indicate that the hydrogen capacity of the MAX phase can be significantly improved by doping an appropriate atom species.

Perioperative Extracorporeal Membrane Oxygenation Support for Acute Respiratory Distress Syndrome Aggravated by Hepatopulmonary Syndrome in Deceased Donor Liver Transplantation: A Case Report.

Background: Extracorporeal membrane oxygenation (ECMO) is an accommodation of the cardiopulmonary bypass technique that can support gas exchange and hemodynamic stability. It is used as a salvage maneuver in patients with life-threatening respiratory or cardiac failure that does not respond to conventional treatment. There are few case reports of successful perioperative use of ECMO, especially preoperatively, in liver transplantation (LT). Here, we report an experience of successful anesthetic management in deceased donor liver transplantation (DDLT) by applying perioperative veno-venous (VV) ECMO support in the setting of acute respiratory distress syndrome (ARDS) aggravated by hepatopulmonary syndrome (HPS). Case: A 25-year-old female (156.0 cm, 65.0 kg), without any underlying disease, was referred to our emergency department for decreased mentality. Based on imaging and laboratory tests, she was diagnosed with acute liver failure of unknown cause combined with severe ARDS aggravated by HPS. Since the patient faced life-threatening hypoxemia with a failure of conventional ventilation maneuvers, preoperative VV ECMO was initiated and maintained during the operation. The patient remained hemodynamically stable throughout DDLT, and ARDS showed gradual improvement after the administration of VV ECMO. As ARDS improved, the patient's condition alleviated, and VV ECMO was weaned on postoperative day 6. Conclusions: This case demonstrates that VV ECMO may be a useful therapeutic option not only during the intraoperative and postoperative periods but also in the preoperative period for patients with liver failure combined with reversible respiratory failure.

Comparison of Postoperative Nausea and Vomiting Incidence between Remimazolam and Sevoflurane in Tympanoplasty with Mastoidectomy: A Single-Center, Double-Blind, Randomized Controlled Trial.

Background and Objectives: Postoperative nausea and vomiting (PONV) is a common adverse effect of general anesthesia, especially in middle ear surgery. Remimazolam is a newer benzodiazepine recently approved for use in general anesthesia. This study aimed to compare the incidence rate of PONV after tympanoplasty with mastoidectomy between using remimazolam and sevoflurane. Materials and Methods: This study included 80 patients undergoing elective tympanoplasty with mastoidectomy. The patients were randomly assigned to either the remimazolam or sevoflurane group. The primary outcome was the incidence rate of PONV 12 h after surgery. The secondary outcomes were the incidence rate of PONV 12-24 and 24-48 h after surgery, severity of PONV, incidence rate of vomiting, administration of rescue antiemetics, hemodynamic stability, and recovery profiles. Results: The incidence rate of PONV 0-12 h after tympanoplasty with mastoidectomy was significantly lower in the remimazolam group compared with that in the sevoflurane group (28.9 vs. 57.9%; p = 0.011). However, the incidence rate of delayed PONV did not differ between the two groups. PONV severity in the early periods after the surgery was significantly lower in the remimazolam group than in the sevoflurane group. The incidence rate of adverse hemodynamic events was lower in the remimazolam group than in the sevoflurane group, but there was no difference in the overall trends of hemodynamic data between the two groups. There was no difference in recovery profiles between the two groups. Conclusions: Remimazolam can significantly reduce the incidence rate of early PONV after tympanoplasty with mastoidectomy under general anesthesia.

Quercetin and Isorhamnetin Reduce Benzo[a]pyrene-Induced Genotoxicity by Inducing RAD51 Expression through Downregulation of miR-34a.

Benzo[a]pyrene (B[a]P) is metabolized in the liver into highly reactive mutagenic and genotoxic metabolites, which induce carcinogenesis. The mutagenic factors, including B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) and reactive oxygen species, generated during B[a]P metabolism can cause DNA damage, such as BPDE-DNA adducts, 8-oxo-dG, and double-strand breaks (DSBs). In this study, we mechanistically investigated the effects of quercetin and its major metabolite isorhamnetin on the repair of B[a]P-induced DNA DSBs. Whole-transcriptome analysis showed that quercetin and isorhamnetin each modulate the expression levels of genes involved in DNA repair, especially those in homologous recombination. RAD51 was identified as a key gene whose expression level was decreased in B[a]P-treated cells and increased by quercetin or isorhamnetin treatment. Furthermore, the number of γH2AX foci induced by B[a]P was significantly decreased by quercetin or isorhamnetin, whereas RAD51 mRNA and protein levels were increased. Additionally, among the five microRNAs (miRs) known to downregulate RAD51, miR-34a level was significantly downregulated by quercetin or isorhamnetin. The protective effect of quercetin or isorhamnetin was lower in cells transfected with a miR-34a mimic than in non-transfected cells, and the B[a]P-induced DNA DSBs remained unrepaired. Our results show that quercetin and isorhamnetin each upregulates RAD51 by downregulating miR-34a and thereby suppresses B[a]P-induced DNA damage.

DJMol: An open-source modeling platform for computational chemistry and materials science with a Python interpreter.

We present a modular and extendable software suite, DJMol, for performing molecular simulations and it is demonstrated with DFTB+, Siesta, Atomic Simulation Environment, and OpenMD codes. It supports many of the standard features of an integrated development environment and consists of a structure builder and viewer, which could be connected with these electronic structure codes along with a set of data analyzers. This program comprises Java and Python modules and its libraries to carry out a different set of modeling tasks in materials science and chemistry. By adopting a Python interpreter into the software, a range of scriptable Python codes, such as Pymatgen can be incorporated into this programmable modeling platform. DJMol, through its common application programming interface (API), supports multiple modeling codes in the backend and several post-processing tools. It benefits an experienced user by increasing efficiency, while a nonexpert user by easy to use API.

Cooperation and competition between magnetism and chemisorption.

Chemisorption on ferromagnetic and non-magnetic surfaces is discussed within the Newns-Anderson-Grimley model along with the Stoner model of ferromagnetism. In the case of ferromagnetic surfaces, the adsorption energy is formulated in terms of the change in surface magnetic moments. Using such a formulation, we address the issue of how an adsorbate's binding strength depends on the magnetic moments of the surface and how the adsorption process reduces/enhances the magnetic moments of the surface. Our results indicate a possible scaling relationship of adsorption energy in terms of surface magnetic moments. In the case of non-magnetic surfaces, we formulate a modified Stoner criterion and discuss the condition for the appearance of magnetism due to chemisorption on an otherwise non-magnetic surface.

Population analysis with Wannier orbitals.

We formulate Wannier orbital overlap population and Wannier orbital Hamilton population to describe the contribution of different orbitals to electron distribution and their interactions. These methods, which are analogous to the well-known crystal orbital overlap population and crystal orbital Hamilton population, provide insight into the distribution of electrons at various atom centers and their contributions to bonding. We apply this formalism in the context of a plane-wave density functional theory calculation. This method provides a means to connect the non-local plane-wave basis to a localized basis by projecting the wave functions from a plane-wave density functional theory calculation to a localized Wannier orbital basis. The main advantage of this formulation is that the spilling factor is strictly zero for insulators and can systematically be made small for metals. We use our proposed method to study and obtain bonding and electron localization insights in five different materials.

Association between the high risk for obstructive sleep apnea and intracranial carotid artery calcification in patients with acute ischemic stroke.

PURPOSE: Obstructive sleep apnea (OSA) is an independent risk factor for stroke. Furthermore, intracranial carotid artery calcification (ICAC) is a marker for subclinical atherosclerosis and future cardiovascular events. We investigated the association between the high risk for OSA and ICAC in patients with acute ischemic stroke. METHODS: We retrospectively investigated 73 patients who were admitted to the hospital with acute ischemic stroke in the internal carotid artery (ICA) territory due to large-artery atherosclerosis. The risk for OSA was assessed using the Berlin Questionnaire, and patients were classified into low-risk (LR-OSA) and high-risk groups (HR-OSA). We compared the burden of ICAC between the two groups. Univariable and multivariable analyses were conducted to investigate the association of high risk for OSA with the presence of calcium in intracranial ICA. RESULTS: The HR-OSA group of 35 patients (48%) was significantly older and had a higher rate of hypertension and diabetes mellitus than the LR-OSA group. The HR-OSA group had more frequent ICAC (92% vs. 63%, p < 0.001), higher Agatston score (162.0 vs. 8.5, p < 0.001), and greater total volume of ICAC (261.2 mm3 vs. 20.1 mm3, p < 0.001) in the intracranial ICA. Presence of calcium in symptomatic intracranial ICA was positively correlated with age (odds ratio, OR, 1.432; 95% confidence interval, CI, 1.098-1.868) and HR-OSA (OR, 18.272; 95% CI, 0.500-668.401) in multivariable logistic regression analysis. CONCLUSIONS: This study showed that the presence of calcium in symptomatic intracranial ICA was related to high risk for OSA in patients with acute ischemic stroke.

Decreased Incidence of Methicillin-Resistant Staphylococcus aureus Bacteremia in Intensive Care Units: a 10-Year Clinical, Microbiological, and Genotypic Analysis in a Tertiary Hospital.

There are limited long-term data on the trends in incidence and characteristics of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB) in intensive care units (ICUs) in which infection control measures have been adopted. We evaluated the trend of incidence and changes in characteristics of MRSA bacteremia in ICUs at a tertiary-care hospital over 10 years using prospective cohort data. ICU-acquired bacteremia was defined as S. aureus bacteremia (SAB) that occurred 48 h or more after ICU admission. MRSA isolates were collected and subjected to microbiological and genotypic analyses. A total of 529 SAB episodes were identified among 367,175 ICU patients. Of these episodes, 288 (54.4%) were ICU acquired, 238 (82.6%) of which were MRSAB. The incidence density of ICU-acquired MRSAB decreased from 1.32 per 1,000 patient-days to 0.19 per 1,000 patient-days (a decrease of 20% annually; P < 0.001 for trend), whereas that of non-ICU-acquired MRSAB fluctuated and did not decrease significantly. The decline in ICU-acquired MRSAB was due to lower catheter-related infection and less pneumonia. Rates of persistent bacteremia and 12-week mortality also fell significantly. A total of 183 isolates were collected from 238 ICU-acquired MRSAB cases. There were no significant changes in the geometric means of vancomycin MICs, vancomycin heteroresistance, or the sequence types of MRSA isolates over time. Chlorhexidine MICs decreased (P < 0.001 for trend) in association with a decline in frequency of the qacA or qacB gene that was related to reductions in specific spa types. The incidence of MRSAB in ICUs has decreased dramatically over time, but most of the microbiological and genotypic characteristics of MRSA isolates have not changed.

Antagonistic Effect of Colistin on Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus in In Vitro and In Vivo Studies.

As concerns arise that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concurrent colistin administration, we evaluated the effect of colistin on vancomycin efficacy against MRSA via in vitro and in vivo studies. Among MRSA blood isolates collected in a tertiary-care hospital, we selected representative strains from community-associated MRSA strains (CA-MRSA; ST72-MRSA-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA; ST5-MRSA-SCCmec II). USA CA-MRSA (USA300), HA-MRSA (USA100), N315 (New York/Japan clone), and a MRSA standard strain (ATCC 43300) were used for comparison. We performed checkerboard assays to identify changes in the vancomycin MIC of MRSA following colistin exposure and evaluated the effect of a vancomycin-colistin combination using time-kill assays. We also assessed the in vivo antagonistic effect by administering vancomycin, colistin, and a combination of these two in a neutropenic murine thigh infection model. In the checkerboard assays, vancomycin MICs of all MRSA strains except N315 were increased by from 0.25 to 0.75 µg/ml following colistin exposure. However, the time-kill assays indicated antagonism only against ST5-MRSA and USA100, when the vancomycin concentration was twice the MIC. In the murine thigh infection model with ST5-MRSA and USA100, vancomycin monotherapy reduced the number of CFU/muscle >1 log10 compared to a combination treatment after 24 h in ST5-MRSA, indicating an antagonistic effect of colistin on vancomycin treatment. This study suggests that exposure to colistin may reduce the susceptibility to vancomycin of certain MRSA strains. Combination therapy with vancomycin and colistin for multidrug-resistant pathogens might result in treatment failure for concurrent MRSA infection.

Expansion of Azulenes as Nonbenzenoid Aromatic Compounds for C-H Activation: Rhodium- and Iridium-Catalyzed Oxidative Cyclization of Azulene Carboxylic Acids with Alkynes for the Synthesis of Azulenolactones and Benzoazulenes.

Rhodium-catalyzed oxidative [4 + 2] cyclization reactions through the C-H activation of azulene carboxylic acids as nonbenzenoid aromatic compounds with symmetrical and unsymmetrical alkynes were developed under aerobic conditions, which produced azulenolactone derivatives with a wide substrate scope and excellent functional group tolerance. Interestingly, azulenic acids in reaction with alkynes underwent iridium-catalyzed [2 + 2 + 2] cyclization accompanied by decarboxylation to afford tetra(aryl)-substituted benzoazulene derivatives. The reactivity order for C-H activation reaction is greater toward azulene-6-carboxylic acid, azulene-1-carboxylic acid, and azulene-2-carboxylic acid. For the first time, the expansion of azulenes having directing group as nonbenzenoid aromatic compounds for C-H activation was successful, indicating that nonbenzenoid aromatic compounds can be used as good substrates for the C-H activation reaction. Therefore, the research area of C-H activation will certainly expand to nonbenzenoid aromatic compounds in future.

Impact of neutropenia on the clinical outcomes of Staphylococcus aureus bacteremia in patients with hematologic malignancies: a 10-year experience in a tertiary care hospital.

Staphylococcus aureus bacteremia is one of the most serious bacterial infections and may lead to worse clinical outcomes in patients with prolonged severe neutropenia. However, clinical data on S. aureus bacteremia in neutropenic patients with hematologic malignancies are limited. We conducted two case-control studies using a 10-year prospective cohort of patients with S. aureus bacteremia. Neutropenic and non-neutropenic hematologic malignancy patients were compared on clinical characteristics and treatment outcomes. An additional matched case-control study using solid tumor patients was conducted. Risk factors for 12-week mortality were analyzed. Of 1643 patients with S. aureus bacteremia, 64 (3.9%) neutropenic and 108 (6.6%) non-neutropenic patients with hematologic malignancies were included in the study. There were no significant differences in the incidence of metastatic infection between the two groups (17.2% vs. 17.6%, p = 0.95), in contrast with a previous study that observed no metastatic infection in neutropenic patients. Twelve-week mortality in neutropenic patients with hematologic malignancies tended to be lower than in non-neutropenic patients with hematologic malignancies (15.6% vs. 26.9%, p = 0.09) and was significantly lower than in neutropenic patients with solid tumors (15.6% vs. 45.8%, p = 0.003). Independent risk factors for mortality in hematologic malignancy patients with S. aureus bacteremia were high Charlson comorbidity score, high APACHE II score, and skin and soft tissue infection. Neutropenia was not independently associated with mortality. Our findings suggest that neutropenia in hematologic malignancies may not affect the incidence of metastatic infection or 12-week mortality of S. aureus bacteremia.

Adsorption energy scaling relation on bimetallic magnetic surfaces: role of surface magnetic moments.

The scaling relationships between the adsorption energies of different reaction intermediates have a tremendous effect in the field of surface science, particularly in predicting new catalytic materials. In the last few decades, these scaling laws have been extensively studied and interpreted by a number of research groups which makes them almost universally accepted. In this work, we report the breakdown of the standard scaling law in magnetic bimetallic transition metal (TM) surfaces for hydrogenated species of oxygen (O), carbon (C), and nitrogen (N), where the adsorption energies are estimated using density functional theory (DFT). We propose that the scaling relationships do not necessarily rely solely on the adsorbates, they can also be strongly dependent on the surface properties. For magnetic bimetallic TM surfaces, the magnetic moment plays a vital role in the estimation of adsorption energy, and therefore towards the linear scaling relation.

Machine Learning and Scaling Laws for Prediction of Accurate Adsorption Energy.

Finding an "ideal" catalyst is a matter of great interest in the communities of chemists and material scientists, partly because of its wide spectrum of industrial applications. Information regarding a physical parameter termed "adsorption energy", which dictates the degrees of adhesion of an adsorbate on a substrate, is a primary requirement in selecting the catalyst for catalytic reactions. Both experiments and in silico modeling are extensively being used in estimating the adsorption energies, both of which are an Edisonian approach, demand plenty of resources, and are time-consuming. In this paper, employing a data-mining approach, we predict the adsorption energies of monoatomic and diatomic gases on the surfaces of many transition metals (TMs) in no time. With less than a set of 10 simple atomic features, our predictions of the adsorption energies are within a root-mean-squared error (RMSE) of 0.4 eV with the quantum many-body perturbation theory estimates, a computationally expensive method with a good experimental agreement. Based on the important features obtained from machine learning models, we construct a set of mathematical equations using the compressed sensing technique to calculate adsorption energy. We also show that the RMSE can be further minimized up to 0.10 eV using the precomputed adsorption energies obtained with the conventional exchange and correlation (XC) functional by a new set of scaling relations.

Bonded Cumomer Analysis of Human Melanoma Metabolism Monitored by 13C NMR Spectroscopy of Perfused Tumor Cells.

A network model for the determination of tumor metabolic fluxes from (13)C NMR kinetic isotopomer data has been developed and validated with perfused human DB-1 melanoma cells carrying the BRAF V600E mutation, which promotes oxidative metabolism. The model generated in the bonded cumomer formalism describes key pathways of tumor intermediary metabolism and yields dynamic curves for positional isotopic enrichment and spin-spin multiplets. Cells attached to microcarrier beads were perfused with 26 mm [1,6-(13)C2]glucose under normoxic conditions at 37 °C and monitored by (13)C NMR spectroscopy. Excellent agreement between model-predicted and experimentally measured values of the rates of oxygen and glucose consumption, lactate production, and glutamate pool size validated the model. ATP production by glycolytic and oxidative metabolism were compared under hyperglycemic normoxic conditions; 51% of the energy came from oxidative phosphorylation and 49% came from glycolysis. Even though the rate of glutamine uptake was ∼ 50% of the tricarboxylic acid cycle flux, the rate of ATP production from glutamine was essentially zero (no glutaminolysis). De novo fatty acid production was ∼ 6% of the tricarboxylic acid cycle flux. The oxidative pentose phosphate pathway flux was 3.6% of glycolysis, and three non-oxidative pentose phosphate pathway exchange fluxes were calculated. Mass spectrometry was then used to compare fluxes through various pathways under hyperglycemic (26 mm) and euglycemic (5 mm) conditions. Under euglycemic conditions glutamine uptake doubled, but ATP production from glutamine did not significantly change. A new parameter measuring the Warburg effect (the ratio of lactate production flux to pyruvate influx through the mitochondrial pyruvate carrier) was calculated to be 21, close to upper limit of oxidative metabolism.

Mechanism of antineoplastic activity of lonidamine.

Lonidamine (LND) was initially introduced as an antispermatogenic agent. It was later found to have anticancer activity sensitizing tumors to chemo-, radio-, and photodynamic-therapy and hyperthermia. Although the mechanism of action remained unclear, LND treatment has been known to target metabolic pathways in cancer cells. It has been reported to alter the bioenergetics of tumor cells by inhibiting glycolysis and mitochondrial respiration, while indirect evidence suggested that it also inhibited l-lactic acid efflux from cells mediated by members of the proton-linked monocarboxylate transporter (MCT) family and also pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier (MPC). Recent studies have demonstrated that LND potently inhibits MPC activity in isolated rat liver mitochondria (Ki 2.5µM) and cooperatively inhibits l-lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevis oocytes with K0.5 and Hill coefficient values of 36-40µM and 1.65-1.85, respectively. In rat heart mitochondria LND inhibited the MPC with similar potency and uncoupled oxidation of pyruvate was inhibited more effectively (IC50~7µM) than other substrates including glutamate (IC50~20µM). LND inhibits the succinate-ubiquinone reductase activity of respiratory Complex II without fully blocking succinate dehydrogenase activity. LND also induces cellular reactive oxygen species through Complex II and has been reported to promote cell death by suppression of the pentose phosphate pathway, which resulted in inhibition of NADPH and glutathione generation. We conclude that MPC inhibition is the most sensitive anti-tumour target for LND, with additional inhibitory effects on MCT-mediated l-lactic acid efflux, Complex II and glutamine/glutamate oxidation.

Regulation of transport properties by polytypism: a computational study on bilayer MoS2.

Being a member of the van der Waals class of solids, bilayer MoS2 exhibits polytypism due to different possible stacking arrangements, namely, 2Hc, 2Ha and 3R-polytypes. Unlike monolayer MoS2, these bilayers exhibit indirect band gaps. Band extrema states originate from a linear combination of Mo-(d) and S-(p) orbitals which are sensitive to the interlayer interactions. We have studied the impact of stacking pattern on the electronic structure and electron/hole transport properties of these polytypes. Based on first-principles computations coupled with the Boltzmann transport formalism, we found that a strong electron-hole anisotropy can be realised in the 2Ha-MoS2 polytype unlike in a monolayer which is isotropic in nature. A staggered arrangement between two layers results in a higher relaxation time for electrons compared to holes leading to anisotropy which is of importance in device engineering.