Feasibility, Safety, Enjoyment, and System Usability of Web-Based Aerobic Dance Exercise Program in Older Adults: Single-Arm Pilot Study.

BACKGROUND: During the COVID-19 epidemic, opportunities for social interaction and physical activity among older people are decreasing, which may have a negative impact on their health. As a solution, a web-based group exercise program provided through a videoconferencing platform would be useful. As a web-based exercise program that older adults can easily, safely, and enjoyably perform at home, we developed a short-duration, light-intensity aerobic dance exercise program. Before studying the effectiveness of this exercise program, its characteristics, such as feasibility, safety, enjoyment, and system usability, should be examined among older adults. OBJECTIVE: This pilot study aimed to examine the feasibility, safety, and enjoyment of a web-based aerobic dance exercise program and the usability of a web-based exercise delivery system using a videoconferencing platform for older adults. METHODS: This study was designed as a prospective single-arm pilot study. A total of 16 older adults participated in an 8-week web-based aerobic dance program held every morning (8:30 AM to 8:50 AM) on weekdays at home. Retention and adherence rates were measured for the program's feasibility. Safety was assessed by the heart rate reserve, an index of exercise intensity calculated from heart rate, and the number of adverse events during exercise sessions. Enjoyment of this exercise program was assessed by an 11-point Likert scale ranging from 0 (not enjoyable at all) to 10 (extremely enjoyable) obtained through telephone interviews after the first-, third-, sixth-, and eighth-week intervention. For usability, the ease of the videoconferencing platform system was assessed through telephone interviews after the intervention. RESULTS: A female participant with hypertension dropped out in the second week because of the continuously reported high blood pressure (≥180 mmHg) before attending the exercise session in the first week. Therefore, the retention rate was 93.8% (15/16). Among the remaining participants, the median (IQR) overall adherence rate was 97.4% (94.7-100). Regarding safety, the mean (SD) heart rate reserve during the aerobic dance exercise was 29.8% (6.8%), showing that the exercise was relatively safe with very light to light intensity. There were no adverse events during the exercise session. The enjoyment score (0-10 points) significantly increased from the first (6.7 [1.7]) to sixth (8.2 [1.3]) and eighth week (8.5 [1.3]). Regarding usability, 11 participants reported difficulties at the beginning, such as basic touch panel operations and the use of unfamiliar applications; however, all got accustomed to it and subsequently reported no difficulty. CONCLUSIONS: This study showed high feasibility, enjoyment, and safety of the web-based aerobic dance exercise program in older adults, and the web-based exercise delivery system may have areas for improvement, albeit without serious problems. Our web-based aerobic dance exercise program may contribute to an increase in physical and social activities among older adults.

Twist Angle-Dependent Molecular Intercalation and Sheet Resistance in Bilayer Graphene.

Bilayer graphene (BLG) has a two-dimensional (2D) interlayer nanospace that can be used to intercalate molecules and ions, resulting in a significant change of its electronic and magnetic properties. Intercalation of BLG with different materials, such as FeCl3, MoCl5, Li ions, and Ca ions, has been demonstrated. However, little is known about how the twist angle of the BLG host affects intercalation. Here, by using artificially stacked BLG with controlled twist angles, we systematically investigated the twist angle dependence of intercalation of metal chlorides. We discovered that BLG with high twist angles of >15° is more favorable for intercalation than BLG with low twist angles. Density functional theory calculations suggested that the weaker interlayer coupling in high twist angle BLG is the key for effective intercalation. Scanning transmission electron microscope observations revealed that co-intercalation of AlCl3 and CuCl2 molecules into BLG gives various 2D structures in the confined interlayer nanospace. Moreover, before intercalation we observed a significantly lower sheet resistance in BLG with high twist angles (281 ± 98 Ω/□) than that in AB stacked BLG (580 ± 124 Ω/□). Intercalation further decreased the sheet resistance, reaching values as low as 48 Ω/□, which is the lowest value reported so far for BLG. This work provides a twist angle-dependent phenomenon, in which enhanced intercalation and drastic changes of the electrical properties can be realized by controlling the stacking angle of adjacent graphene layers.

The effect of the low stromal ratio induced by neoadjuvant chemotherapy on recurrence patterns in borderline resectable pancreatic ductal adenocarcinoma.

The optimal regimens of neoadjuvant chemotherapy (NAC) and its biological and physiological modification of the tumor microenvironment (TME) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) remain unknown. A deeper understanding of the complex stromal biology of the TME will identify new avenues to establish treatment strategies for PDAC patients. Herein, we sought to clarify whether stromal remodeling by NAC affects recurrence patterns and prognosis in BR PDAC patients. We retrospectively analyzed data from 104 BR PDAC patients who underwent pancreatectomy with or without NAC (upfront surgery [UpS], n = 44; gemcitabine + nab-paclitaxel [GnP], n = 28; and gemcitabine + S-1 [GS], n = 32) to assess the correlations of treatment with early recurrence, the stromal ratio, and Ki-67 levels. Eighty-six patients experienced recurrence, and those with liver metastasis had significantly shorter recurrence-free survival than those with other recurrence patterns. The frequency of liver metastasis was significantly higher in patients with a low stromal ratio than in those with a high stromal ratio in the NAC group but not in the UpS group. Patients in the GnP group had significantly higher Ki-67 than those in the GS and UpS groups. A low stromal ratio was positively correlated with high Ki-67 in the NAC group but not in the UpS group. The low stromal ratio induced by NAC promoted early liver metastasis in patients with BR PDAC. Our findings provide new insights into the complexity of stromal biology, leading to consideration of the optimal NAC regimen.

Isothermal Growth and Stacking Evolution in Highly Uniform Bernal-Stacked Bilayer Graphene.

Controlling the stacking order in bilayer graphene (BLG) allows realizing interesting physical properties. In particular, the possibility of tuning the band gap in Bernal-stacked (AB) BLG (AB-BLG) has a great technological importance for electronic and optoelectronic applications. Most of the current methods to produce AB-BLG suffer from inhomogeneous layer thickness and/or coexistence with twisted BLG. Here, we demonstrate a method to synthesize highly pure large-area AB-BLG by chemical vapor deposition using Cu-Ni films. Increasing the reaction time resulted in a gradual increase of the AB stacking, with the BLG eventually free from twist regions for the longer growth times (99.4% of BLG has AB stacking), due to catalyst-assisted continuous BLG reconstruction driven by carbon dissolution-segregation processes. The band gap opening was confirmed by the electrical measurements on field-effect transistors using two different device configurations. The concept of the continuous reconstruction to achieve highly pure AB-BLG offers a way to control the stacking order of catalytically grown two-dimensional materials.

[Laparoscopic Partial Colectomy for Transverse Colon Cancer after Open Laparotomy for Gastric Cancer Resection].

We report a case of transverse colon cancer resected by laparoscopic partial colectomy, followed by open gastrectomy. A man in his 70s was diagnosed with transverse colon cancer. He had a history of open gastrectomy for gastric lymphoma; thus, postoperative adhesions were expected in the upper abdomen. We performed a laparoscopic partial colectomy with gentle adhesiotomy, without injury. After preparation of the marginal vessels, blood flow towards the planned anastomotic line was confirmed by infrared observation after venous injection of indocyanine green. However, the initially planned oral anastomotic line did not show a blood supply; therefore, the anastomotic line was altered to a site of sufficient blood flow. In postlaparotomy cases, delicate handling and careful adhesiotomy are necessary in the laparoscopic approach due to the possibility of severe intraoperative injury resulting in conversion to open surgery. Furthermore, blood flow confirmation by fluorescence angiography is recommended in cases in which anatomical alterations might have occurred due to the previous operation.

Outcomes of surgical resection for gastric cancer liver metastases: a retrospective analysis.

BACKGROUND: The indications for the surgical treatment of gastric cancer liver metastases (GCLMs) remain controversial. In addition, the outcome of surgery for the treatment of liver metastases of alpha-fetoprotein-producing gastric cancer (AFP-GC) has not yet been reported. We assessed the clinicopathologic features, including AFP-GC, and the surgical results of these patients. METHODS: This retrospective study analyzed 20 patients who underwent hepatectomy for GCLM at Odawara Municipal Hospital between April 2006 and January 2016. RESULTS: The actuarial 1-, 3-, and 5-year overall survival (OS) rates after primary hepatectomy were 80.0%, 55.5%, and 31.7%, respectively, with a median OS of 42 months. Four patients survived for more than 5 years after their final hepatectomy procedures. A multivariate analysis showed multiple metastases in the liver, the elevated level of carbohydrate antigen 19-9 (CA19-9), and an age of less than 70 years to be independently associated with a poor prognosis in terms of OS. No significant differences were noted between the AFP-GC and AFP-negative GC groups. CONCLUSION: Surgical treatment is therefore considered to be a feasible option for GCLM. The findings of the present study showed the number of metastatic liver tumors, the level of CA19-9, and the patient age to be prognostic indicators for the surgical treatment of GCLM.

Surgical treatment strategy for esophagogastric junction cancers based on the tumor diameter.

BACKGROUND: The number of patients with esophagogastric junction (EGJ) cancers has tended to increase. However, no clear consensus on the optimum treatment policy has yet been reached. METHODS: This study included patients diagnosed with adenocarcinoma of Sievert type II in whom resection was performed in our hospital. We performed a clinicopathological examination, and patients were divided into two groups by the tumor size: L group, tumor size ≥4 cm; and S group, tumor size < 4 cm. The clinical factors, such as nodal dissection and recurrence pattern, were then analyzed. RESULTS: A total of 48 patients were diagnosed with ECJ cancers. The average tumor size was 55.1 mm, and 32 cases (66.7%) had tumors ≥4 cm. Metastasis to the mediastinum was noted in 4 cases (12.5%) in the L group but none in the S group. Recurrence in the upper or middle mediastinum lymph nodes was noted in 3 cases (9.4%) in the L group. The 5-year overall survival rates were 49.7 and 83.9% in the L and S groups, respectively. CONCLUSIONS: As the tumor grows large, it is difficult to accurately judge EGJ on the image, and as a result it is difficult to understand the exact esophageal invasion distance of the tumor. Therefore, lymph node dissection including the upper mediastinum is considered vital, regardless of the degree of esophageal invasion.

Synthesis of sub-millimeter single-crystal grains of aligned hexagonal boron nitride on an epitaxial Ni film.

Hexagonal boron nitride (h-BN), an insulating two-dimensional (2D) layered material, has attracted increasing interest due to its electrical screening effect, high-temperature-resistant gas barrier properties, and other unique applications. However, the presence of grain boundaries (GBs) in h-BN is a hindrance to obtain these properties. Here, we demonstrate the epitaxial growth of monolayer h-BN by chemical vapor deposition (CVD) on Ni(111) thin films deposited on c-plane sapphire. The Ni(111) films showed higher thermal stability than Cu(111) and Cu-Ni(111) alloy films, allowing us to perform CVD growth at a high temperature of 1100 °C. This resulted in an increase of the h-BN grain sizes to up to 0.5 millimeter, among the highest reported so far, and in a well-defined triangular grain shape. Low-energy electron microscopy (LEEM) revealed the epitaxial relationship between h-BN and the underlying Ni(111) lattice, leading to a preferential alignment of the h-BN grains. Both the large grain size and the alignment are expected to facilitate the synthesis of h-BN with a low density of GBs. We also found that the addition of N2 gas during the CVD improves the crystalline shape of the h-BN grains, changing from an irregular, truncated to a sharp triangle. The growth behavior of monolayer h-BN is further discussed in terms of the dependences on growth temperature and pressure, as well as on the structural evolution of the Ni metal catalyst. Our findings not only help understand the h-BN growth mechanism but also offer a new route to grow high-quality, monolayer h-BN films.

A novel graphene barrier against moisture by multiple stacking large-grain graphene.

The moisture barrier properties of stacked graphene layers on Cu surfaces were investigated with the goal of improving the moisture barrier efficiency of single-layer graphene (SLG) for Cu metallization. SLG with large grain size were stacked on Cu surfaces coated with CVD-SLG to cover the grain-boundaries and defective areas of the underneath SLG film, which was confirmed to be oxidized by Raman spectroscopy measurements. To evaluate the humidity resistance of the graphene-coated Cu surfaces, temperature humidity storage (THS) testing was conducted under accelerated oxidation conditions (85 °C and 85% relative humidity) for 100 h. The color changes of the Cu surfaces during THS testing were observed by optical microscopy, while the oxidized Cu into Cu2O and CuO was detected by X-ray photoelectron spectroscopy (XPS). The experimental results were accord with the results of first-principle simulation for the energetic barrier against water diffusion through the stacked graphene layers with different overlap. The results demonstrate the efficiency of SLG stacking approach against moisture for Cu metallization.

[Results of Neoadjuvant Chemotherapy with S-1 plus CDDP for Gastric Cancer-The Number of Therapeutic Coursers and Therapeutic Effects].

Neoadjuvant chemotherapy(NAC)with S-1 plus CDDP(SP)followed by gastrectomy has been used for the treatment of patients with locally advanced gastric cancer. We examined the number of treatment courses, histologic effects, ypStage, and prognosis to estimate the utility and define the best treatment course of SP NAC. The patients were divided into 1 course(A: 54 cases), 2 courses(B: 50 cases), and incomplete first course(C: 12 cases). The rates of Grade 2 or more in histological effect were 24.1% in group A, 34.0% in B, and 0% in C. Four patients achieved pathological CR(1 case in group A and 3 cases in group B). The pathological response by NAC was more effective in group B than in group A. In down-staging cases by NAC, survival curves were obtained according to ypStage. The 5-year survival rates in R0 cases were 67.0%in the effective therapeutic group and 51.0%in the non-effective group; the results being significantly different. According to the number of therapeutic courses of NAC, the 5-year survival rates were 57.9% in group A, 65.2% in group B, and 20.0% in group C, demonstrating a significantly better prognosis in group B. Although the pathological response appeared in 1 course, it was significant in 2 courses of NAC. The results indicate that the completion of at least 2 courses of NAC are necessary in locally advanced gastric cancer.

[Laparoscopic Gastro-Jejunostomy Using the Overlap Method after Subtotal Gastrectomy for Upper Gastric Cancer].

BACKGROUND: Due to an aging society, patients with gastric cancer are also getting older. Although total gastrectomy should be avoided for elderly patients, laparoscopic subtotal gastrectomy(LSTG)is a technically demanding procedure. Here, we present a safe procedure of gastro-jejunostomy using the overlap method. METHODS: After transection of the stomach using gastroscopy, an entry hole was created at the center of the staple line of the remnant stomach. The jejunum was anastomosed to the dorsal wall of the gastric remnant with a linear stapler, and the entry hole was closed by hand-sewn sutures. Nineteen patients with gastric cancer in the upper third of the stomach underwent LSTG using this technique, and the short-term clinical outcomes were analyzed retrospectively. RESULTS: The median operative time was 221 minutes(143-318), and the median blood loss was 10 mL(3-100). The median postoperative hospital stay was 7 days(6-13), and there were no complications related to anastomosis. CONCLUSIONS: The short-term clinical outcomes of the laparoscopic gastro-jejunostomy using the overlap method after LSTG reveal that this technique is safe and feasible to use for improving patient outcomes.

Surface-Mediated Aligned Growth of Monolayer MoS2 and In-Plane Heterostructures with Graphene on Sapphire.

Aligned growth of transition metal dichalcogenides and related two-dimensional (2D) materials is essential for the synthesis of high-quality 2D films due to effective stitching of merging grains. Here, we demonstrate the controlled growth of highly aligned molybdenum disulfide (MoS2) on c-plane sapphire with two distinct orientations, which are highly controlled by tuning sulfur concentration. We found that the size of the aligned MoS2 grains is smaller and their photoluminescence is weaker as compared with those of the randomly oriented grains, signifying enhanced MoS2-substrate interaction in the aligned grains. This interaction induces strain in the aligned MoS2, which can be recognized from their high susceptibility to air oxidation. The surface-mediated MoS2 growth on sapphire was further developed to the rational synthesis of an in-plane MoS2-graphene heterostructure connected with the predefined orientation. The in-plane epitaxy was observed by low-energy electron microscopy. Transmission electron microscopy and scanning transmission electron microscopy suggest the alignment of a zigzag edge of MoS2 parallel to a zigzag edge of the neighboring graphene. Moreover, better electrical contact to MoS2 was obtained by the monolayer graphene compared with a conventional metal electrode. Our findings deepen the understanding of the chemical vapor deposition growth of 2D materials and also contribute to the tailored synthesis as well as applications of advanced 2D heterostructures.

Controlled Growth of Large-Area Uniform Multilayer Hexagonal Boron Nitride as an Effective 2D Substrate.

Multilayer hexagonal boron nitride (h-BN) is an ideal insulator for two-dimensional (2D) materials, such as graphene and transition metal dichalcogenides, because h-BN screens out influences from surroundings, allowing one to observe intrinsic physical properties of the 2D materials. However, the synthesis of large and uniform multilayer h-BN is still very challenging because it is difficult to control the segregation process of B and N atoms from metal catalysts during chemical vapor deposition (CVD) growth. Here, we demonstrate CVD growth of multilayer h-BN with high uniformity by using the Ni-Fe alloy film and borazine (B3H6N3) as catalyst and precursor, respectively. Combining Ni and Fe metals tunes the solubilities of B and N atoms and, at the same time, allows one to engineer the metal crystallinity, which stimulates the uniform segregation of multilayer h-BN. Furthermore, we demonstrate that triangular WS2 grains grown on the h-BN show photoluminescence stronger than that grown on a bare SiO2 substrate. The PL line width of WS2/h-BN (the minimum and mean widths are 24 and 43 meV, respectively) is much narrower than those of WS2/SiO2 (44 and 67 meV), indicating the effectiveness of our CVD-grown multilayer h-BN as an insulating layer. Large-area, multilayer h-BN realized in this work will provide an excellent platform for developing practical applications of 2D materials.

High-speed and on-chip graphene blackbody emitters for optical communications by remote heat transfer.

High-speed light emitters integrated on silicon chips can enable novel architectures for silicon-based optoelectronics, such as on-chip optical interconnects, and silicon photonics. However, conventional light sources based on compound semiconductors face major challenges for their integration with a silicon-based platform because of their difficulty of direct growth on a silicon substrate. Here we report ultra-high-speed (100-ps response time), highly integrated graphene-based on-silicon-chip blackbody emitters in the near-infrared region including telecommunication wavelength. Their emission responses are strongly affected by the graphene contact with the substrate depending on the number of graphene layers. The ultra-high-speed emission can be understood by remote quantum thermal transport via surface polar phonons of the substrates. We demonstrated real-time optical communications, integrated two-dimensional array emitters, capped emitters operable in air, and the direct coupling of optical fibers to the emitters. These emitters can open new routes to on-Si-chip, small footprint, and high-speed emitters for highly integrated optoelectronics and silicon photonics.

Highly Conductive and Transparent Large-Area Bilayer Graphene Realized by MoCl5 Intercalation.

Bilayer graphene (BLG) comprises a 2D nanospace sandwiched by two parallel graphene sheets that can be used to intercalate molecules or ions for attaining novel functionalities. However, intercalation is mostly demonstrated with small, exfoliated graphene flakes. This study demonstrates intercalation of molybdenum chloride (MoCl5 ) into a large-area, uniform BLG sheet, which is grown by chemical vapor deposition (CVD). This study reveals that the degree of MoCl5 intercalation strongly depends on the stacking order of the graphene; twist-stacked graphene shows a much higher degree of intercalation than AB-stacked. Density functional theory calculations suggest that weak interlayer coupling in the twist-stacked graphene contributes to the effective intercalation. By selectively synthesizing twist-rich BLG films through control of the CVD conditions, low sheet resistance (83 Ω â–«-1 ) is realized after MoCl5 intercalation, while maintaining high optical transmittance (≈95%). The low sheet resistance state is relatively stable in air for more than three months. Furthermore, the intercalated BLG film is applied to organic solar cells, realizing a high power conversion efficiency.

Evaluation of the site specificity of acute disuse muscle atrophy developed during a relatively short period in critically ill patients according to the activities of daily living level: A prospective observational study.

INTRODUCTION: In critically ill patients, excessive bed rest and immobilisation have been shown to cause disuse muscle atrophy, which contributes to prolonged hospitalisation and decreased activity of daily living (ADL) levels. However, the degree and site specificity of acute disuse muscle atrophy in critically ill patients during a relatively short intensive care unit (ICU) stay have not been fully elucidated. METHODS: Critically ill patients, who required bed rest on ICU admission, were eligible for this study. The degree of skeletal muscle atrophy was evaluated on the day of, and 72 and 144h after ICU admission by measuring the limb circumference in ADL-dependent or -independent patients separately at five different sites: the midpoint of the upper limb between the acromion and the olecranon, the maximum diameter of the triceps surae in the lower leg, and three different sites in the thigh at 5, 10, and 15cm above the superior pole of the patella. Value of the limb circumference was presented as a percentage relative to the baseline (median). RESULTS: In ADL-dependent patients, limb circumferences at all five sites were decreased significantly at 144h compared with the baseline (98.9-100% in the upper limbs, 97.1-97.2% in the lower legs, and 96.5-99.1% in the thighs), but not at 72h. In contrast, the limb circumferences at almost all sites decreased significantly at both 72 and 144h (100% in the upper limbs, 94.5-94.7% in the lower legs, and 89.7-94.7% in the thighs), compared with the baseline in ADL-independent patients. Muscle atrophy was greater at the four different lower-limb sites compared to the upper limb during 144h in the ICU in the ADL-independent, but not in the ADL-dependent patients. CONCLUSIONS: Compared to ADL-dependent patients, ADL-independent patients are prone to develop muscle weakness, especially in the lower limbs.

Direct observation of electrically induced Pauli paramagnetism in single-layer graphene using ESR spectroscopy.

Graphene has been actively investigated as an electronic material owing to many excellent physical properties, such as high charge mobility and quantum Hall effect, due to the characteristics of a linear band structure and an ideal two-dimensional electron system. However, the correlations between the transport characteristics and the spin states of charge carriers or atomic vacancies in graphene have not yet been fully elucidated. Here, we show the spin states of single-layer graphene to clarify the correlations using electron spin resonance (ESR) spectroscopy as a function of accumulated charge density using transistor structures. Two different electrically induced ESR signals were observed. One is originated from a Fermi-degenerate two-dimensional electron system, demonstrating the first observation of electrically induced Pauli paramagnetism from a microscopic viewpoint, showing a clear contrast to no ESR observation of Pauli paramagnetism in carbon nanotubes (CNTs) due to a one-dimensional electron system. The other is originated from the electrically induced ambipolar spin vanishments due to atomic vacancies in graphene, showing a universal phenomenon for carbon materials including CNTs. The degenerate electron system with the ambipolar spin vanishments would contribute to high charge mobility due to the decrease in spin scatterings in graphene.

Structure and transport properties of the interface between CVD-grown graphene domains.

During the chemical vapor deposition (CVD) growth of graphene, graphene domains grown on a Cu surface merge together and form a uniform graphene sheet. For high-performance electronics and other applications, it is important to understand the interfacial structure of the merged domains, as well as their influence on the physical properties of graphene. We synthesized large hexagonal graphene domains with controlled orientations on a heteroepitaxial Cu film and studied the structure and properties of the interfaces between the domains mainly merged with the same angle. Although the merged domains have various interfaces with/without wrinkles and/or increased defect-related Raman D-band intensity, the intra-domain transport showed higher carrier mobility reaching 20,000 cm(2) V(-1) s(-1) on SiO2 at 280 K (the mean value was 7200 cm(2) V(-1) s(-1)) than that measured for inter-domain areas, 6400 cm(2) V(-1) s(-1) (mean value 2000 cm(2) V(-1) s(-1)). The temperature dependence of the mobility suggests that impurity scattering dominates at the interface even for the merged domains with the same orientation. This study highlights the importance of domain interfaces, especially on the carrier transport properties, in CVD-grown graphene.

Large-scale synthesis of NbS2 nanosheets with controlled orientation on graphene by ambient pressure CVD.

We report ambient pressure chemical vapor deposition (CVD) growth of single-crystalline NbS2 nanosheets with controlled orientation. On Si and SiO2 substrates, NbS2 nanosheets grow almost perpendicular to the substrate surface. However, when we apply transferred CVD graphene on SiO2 as a substrate, NbS2 sheets grow laterally lying on the graphene. The NbS2 sheets show the triangular and hexagonal shapes with a thickness of about 20-200 nm and several micrometres in the lateral dimension. Analyses based on X-ray diffraction and Raman spectroscopy indicate that the NbS2 nanosheets are single crystalline 3R-type with a rhombohedral structure of R3m space group. Our findings on the formation of highly aligned NbS2 nanosheets on graphene give new insight into the formation mechanism of NbS2 and would contribute to the templated growth of various layered materials.

Mitochondrial dehydrogenases in the aerobic respiratory chain of the rodent malaria parasite Plasmodium yoelii yoelii.

In the intraerythrocytic stages of malaria parasites, mitochondria lack obvious cristae and are assumed to derive energy through glycolysis. For understanding of parasite energy metabolism in mammalian hosts, we isolated rodent malaria mitochondria from Plasmodium yoelii yoelii grown in mice. As potential targets for antiplasmodial agents, we characterized two respiratory dehydrogenases, succinate:ubiquinone reductase (complex II) and alternative NADH dehydrogenase (NDH-II), which is absent in mammalian mitochondria. We found that P. y. yoelii complex II was a four-subunit enzyme and that kinetic properties were similar to those of mammalian enzymes, indicating that the Plasmodium complex II is favourable in catalysing the forward reaction of tricarboxylic acid cycle. Notably, Plasmodium complex II showed IC(50) value for atpenin A5 three-order of magnitudes higher than those of mammalian enzymes. Divergence of protist membrane anchor subunits from eukaryotic orthologs likely affects the inhibitor resistance. Kinetic properties and sensitivity to 2-heptyl-4-hydroxyquinoline-N-oxide and aurachin C of NADH: ubiquinone reductase activity of Plasmodium NDH-II were similar to those of plant and fungus enzymes but it can oxidize NADPH and deamino-NADH. Our findings are consistent with the notion that rodent malaria mitochondria are fully capable of oxidative phosphorylation and that these mitochondrial enzymes are potential targets for new antiplasmodials.