Greater Mekong Subregion Research Articles

Characterizing antibody responses to mosquito salivary antigens of the Southeast Asian vectors of malaria and dengue with a human challenge model of controlled exposure: a protocol.

Background: Measurement of antibody titers directed against mosquito salivary antigens in blood samples has been proposed as an outcome measure to assess human exposure to vector bites. However, only a handful of antigens have been identified and the specificity and longitudinal dynamics of antibody responses are not well known. We report the protocol of a clinical trial of controlled exposure to mosquito bites that aims to identify and validate biomarkers of exposure to bites of mosquito vector species that transmit malaria and dengue in Southeast Asia and some other parts of the world. Methods: This study is an exploratory factorial randomized control trial of controlled exposure to mosquito bites with 10 arms corresponding to different species ( Aedes aegypti, Ae. albopictus, Anopheles dirus, An. maculatus and An. minimus) and numbers of bites (35 or 305 bites in total over 6 weeks). Blood samples will be collected from study participants before, during and after mosquito biting challenges. Candidate peptides will be identified from published literature with antigen prediction algorithms using mosquito DNA sequence data and with immunoblotting assays carried out using protein extracts of dissected mosquito salivary glands and participants samples. Antibody titers against candidate peptides will be determined in participants samples with high-throughput cutting-edge immuno-assays. Quantification of the antibody response profile over time (including an estimate of the decay rate) and the effect of the number of bites on the antibody response will be determined using linear and logistic mixed-effects models for the continuous and the binary response, respectively. Conclusion: This research is expected to generate important knowledge for vector sero-surveillance and evaluation of vector-control interventions against malaria and dengue in the Greater Mekong Subregion. Registration: This study is registered with clinicaltrials.gov (NCT04478370) on July 20 th, 2020.

Harnessing solar and wind for sustainable cross-border electricity trade in the Greater Mekong Subregion

Sustainable, low-emission electricity generation options are needed in the Greater Mekong Subregion, including for cross-border electricity trade. Large-scale investment in solar and wind power, together with off-river pumped hydro energy storage, is identified as a promising way forward. The GMS has many potential off-river pumped hydro sites. Actionable recommendations include greater use of bilateral power purchase agreements for cross-border solar and wind power supply, and potential development of a high-voltage direct current grid. Institutional prioritization and ongoing evaluation are required to ensure desired social, environmental, and economic outcomes from the transition.

1H NMR fecal metabolic phenotyping of periductal fibrosis- and cholangiocarcinoma-specific metabotypes defining perturbation in gut microbial-host co-metabolism.

The liver fluke Opisthorchis viverrini (OV), which subsequently inhabits the biliary system and results in periductal fibrosis (PDF), is one of the primarily causes of cholangiocarcinoma (CCA), a bile duct cancer with an exceptionally high incidence in the northeast of Thailand and other Greater Mekong Subregion (GMS) countries. Insights in fecal metabolic changes associated with PDF and CCA are required for further molecular research related to gut health and potential diagnostic biological marker development. In this study, nuclear magnetic resonance (NMR) metabolomics was applied for fecal metabolic phenotyping from 55 fecal water samples across different study groups including normal bile duct, PDF and CCA groups. By using NMR spectroscopy-based metabolomics, fecal metabolic profiles of patients with CCA or PDF and of individuals with normal bile duct have been established with a total of 40 identified metabolites. Further multivariate statistical analysis and hierarchical clustering heat map have demonstrated the PDF- and CCA-specific metabotypes through various altered metabolite groups including amino acids, alcohols, amines, anaerobic glycolytic metabolites, fatty acids, microbial metabolites, sugar, TCA cycle intermediates, tryptophan catabolism substrates, and pyrimidine metabolites. Compared to the normal bile duct group, PDF individuals showed the significantly elevated relative concentrations of fecal ethanol, glycine, tyrosine, and N-acetylglucosamine whereas CCA patients exhibited the remarkable fecal metabolic changes that can be evident through the increased relative concentrations of fecal uracil, succinate, and 5-aminopentanoate. The prominent fecal metabolic alterations between CCA and PDF were displayed by the reduction of relative concentration of methanol observed in CCA. The metabolic alterations associated with PDF and CCA progression have been proposed with the involvement of various metabolic pathways including TCA cycle, ethanol biogenesis, hexamine pathway, methanol biogenesis, pyrimidine metabolism, and lysine metabolism. Among them, ethanol, methanol, and lysine metabolism strongly reflect the association of gut-microbial host metabolic crosstalk in PDF and/or CCA patients. The PDF- and CCA-associated metabotypes have been investigated displaying their distinct fecal metabolic patterns compared to that of normal bile duct group. Our study also demonstrated that the perturbation in co-metabolism of host and gut bacteria has been involved from the early step since OV infection to CCA tumorigenesis.

Potential Plant-Based New Antiplasmodial Agent Used in Papua Island, Indonesia.

Resistance to antimalarial medicine remains a threat to the global effort for malaria eradication. The World Health Organization recently reported that artemisinin partial resistance, which was defined as delayed parasite clearance, was detected in Southeast Asia, particularly in the Greater Mekong subregion, and in Africa, particularly in Rwanda and Uganda. Therefore, the discovery of a potential new drug is important to overcome emerging drug resistance. Natural products have played an important role in drug development over the centuries, including the development of antimalarial drugs, with most of it influenced by traditional use. Recent research on traditional medicine used as an antimalarial treatment on Papua Island, Indonesia, reported that 72 plant species have been used as traditional medicine, with Alstonia scholaris, Carica papaya, Andrographis paniculata, and Physalis minima as the most frequently used medicinal plants. This review aimed to highlight the current research status of these plants for potential novel antiplasmodial development. In conclusion, A. paniculata has the highest potential to be developed as an antiplasmodial, and its extract and known bioactive isolate andrographolide posed strong activity both in vitro and in vivo. A. scholaris and C. papaya also have the potential to be further investigated as both have good potential for their antiplasmodial activities in vivo. However, P. minima is a less studied medicinal plant; nevertheless, it opens the opportunity to explore the potential of this plant.

Rising temperatures over the Greater Mekong Subregion in CMIP6: Present-day biases and constraint future projections

This study evaluates the historical simulation of surface air temperature (SAT) over the Greater Mekong Subregion (GMS) during the period 1981–2014 with 31 models from Coupled Model Intercomparison Project phase 6 (CMIP6). The CMIP6 multi-model ensemble shows a weaker SAT growth trend than the reanalysis data in all seasons. The SAT increase is underestimated mostly in winter, by around 0.2 °C/decade. The simulated SAT climatology shows positive bias over the Gaoligong Mountain in western Yunnan, the Rakhine Mountain in Myanmar, and the Annamite Range in southern Vietnam, and negative bias elsewhere. We make a best-model ensemble to improve the representability of the GMS SAT. The range of SAT interannual variability is underestimated over most parts of GMS in boreal spring, autumn, and winter. In summer, the SAT range bias shows a dipole pattern with negative bias over the northwestern GMS and positive bias over the southeastern GMS. Dynamical diagnosis suggests that the bias in vertical velocity perturbation, manifesting as weakened regional Hadley circulation, is a major contributor to the SAT range bias in summer via vertical advection of mean potential temperature. The bias-corrected projection of the summer SAT is presented for three shared socio-economic pathways (SSPs). The SAT rising relative to the reference period 1995–2014 tends to be more spatially homogeneous under higher emission scenarios. The range of SAT interannual variability would increase over the northern GMS but decrease over the southern GMS under three SSPs scenarios. This SAT dipole variation is associated with intensified regional Hadley circulation over the GMS. The results also reiterate the urgent need for net zero emission by 2050 to maintain a sustainable environment.

Anthropogenic activities dominated tropical forest carbon balance in two contrary ways over the Greater Mekong Subregion in the 21st century.

The tropical forest carbon (C) balance threatened by extensive socio-economic development in the Greater Mekong Subregion (GMS) in Asia is a notable data gap and remains contentious. Here we generated a long-term spatially quantified assessment of changes in forests and C stocks from 1999 to 2019 at a spatial resolution of 30 m, based on multiple streams of state-of-the-art high-resolution satellite imagery and in situ observations. Our results show that (i) about 0.54 million square kilometers (21.0% of the region) experienced forest cover transitions with a net increase in forest cover by 4.3% (0.11 million square kilometers, equivalent to 0.31 petagram of C [Pg C] stocks); (ii) forest losses mainly in Cambodia, Thailand, and in the south of Vietnam, were also counteracted by forest gains in China due mainly to afforestation; and (iii) at the national level during the study period an increase in both C stocks and C sequestration (net C gain of 0.087 Pg C) in China from new plantation, offset anthropogenetic emissions (net C loss of 0.074 Pg C) mainly in Cambodia and Thailand from deforestation. Political, social, and economic factors significantly influenced forest cover change and C sequestration in the GMS, positively in China while negatively in other countries, especially in Cambodia and Thailand. These findings have implications on national strategies for climate change mitigation and adaptation in other hotspots of tropical forests.

Characterizing antibody responses to mosquito salivary antigens of the Southeast Asian vectors of malaria and dengue with a human challenge model of controlled exposure: a protocol

Background: Measurement of antibody titers directed against mosquito salivary antigens in blood samples has been proposed as an outcome measure to assess human exposure to vector bites. However, only a handful of antigens have been identified and the specificity and longitudinal dynamics of antibody responses are not well known. We report the protocol of a clinical trial of controlled exposure to mosquito bites that aims to identify and validate biomarkers of exposure to bites of mosquito vector species that transmit malaria and dengue in Southeast Asia and some other parts of the world. Methods: This study is an exploratory factorial randomized control trial of controlled exposure to mosquito bites with 10 arms corresponding to different species (Aedes aegypt, Ae. albopictus, Anopheles dirus, An. maculatus and An. minimus) and numbers of bites (35 or 305 bites in total over 6 weeks). Blood samples will be collected from study participants before, during and after mosquito biting challenges. Candidate peptides will be identified from published literature with antigen prediction algorithms using mosquito DNA sequence data and with immunoblotting assays carried out using protein extracts of dissected mosquito salivary glands and participants samples. Antibody titers against candidate peptides will be determined in participants samples with high-throughput cutting-edge immuno-assays. Quantification of the antibody response profile over time (including an estimate of the decay rate) and the effect of the number of bites on the antibody response will be determined using linear and logistic mixed-effects models for the continuous and the binary response, respectively. Conclusion: This research is expected to generate important knowledge for vector sero-surveillance and evaluation of vector-control interventions against malaria and dengue in the Greater Mekong Subregion. Registration: This study is registered with clinicaltrials.gov (NCT04478370) on July 20th, 2020.

Cooperative Governance of Transboundary Water in Greater Mekong Subregion: Challenges in the Lancang-Mekong Cooperation

Rivers not only provide the most basic water resources but also pertain to national strategic resources with crucial implications. When it comes to international relationships, transboundary water management is a major topic under discussion. Nowadays, numerous riparian countries worldwide are involved in the issue of transboundary water governance. Better cooperative governance of transboundary water among countries could facilitate economic progress and enhance sustainable development. This paper took Greater Mekong Subregion (GMS) as a case study, analyzed challenges in the Lancang-Mekong Cooperation, and put forward prospective solutions to address these problems in the hope of deepening the cooperation in managing the shared water resources within the river basin and further providing potential support for worldwide major river basin cooperative governance. By employing a combination of qualitative and quantitative methods, the paper found that current challenges for cooperation in the GMS are mainly: disputes over benefit distribution among countries upstream and downstream, different utilization of water resources and complex coordination, and multi-player games in the GMS.

Community Agricultural Reservoir Construction and Water Supply Network Design in Ubon Ratchathani, Thailand, Using Adjusted Variable Neighborhood Strategy Adaptive Search

Agricultural sectors all over the world are facing water deficiencies as a result of various factors. Countries in the Greater Mekong Subregion (GMS) in particular depend on the production of agricultural products; thus, drought has become a critical problem in such countries. The average water level in the lower part of the Mekong River has been decreasing dramatically, resulting in the wider agricultural area of the Mekong watershed facing a lack of water for production. The construction of community reservoirs and associated water supply networks represents a strategy that can be used to address drought problems in the GMS. This study aims to solve the agricultural community reservoir establishment and water supply network design (CR–WSND) problem in Khong Chiam, Ubon Ratchathani, Thailand—a city located in the Mekong Basin. The CR–WSND model is formulated using mixed-integer programming (MIP) in order to minimize the cost of reservoir construction and water irrigation. An adjusted variable neighborhood strategy adaptive search (A-VaNSAS) is applied to a real-world scenario involving 218 nodes, and its performance is compared with that of the original variable neighborhood strategy adaptive search (VaNSAS), differential evolution (DE), and genetic algorithm (GA) approaches. An improved box selection formula and newly designed improvement black boxes are added to enhance the quality beyond the original VaNSAS. The results reveal that the quality of the solution from A-VaNSAS is significantly better than those of GA, DE, and VaNSAS (by 6.27%, 9.70%, and 9.65%, respectively); thus, A-VaNSAS can be used to design a community reservoir and water supply network effectively.

Private Sector Contributions to National Malaria Surveillance Systems in Elimination Settings: Lessons Learned from Cambodia, Lao PDR, Myanmar, and Vietnam.

Comprehensive malaria case surveillance is necessary to achieve and sustain malaria elimination. In the Greater Mekong Subregion (GMS), the private sector plays a substantial role in malaria treatment. Yet, none of the six GMS countries collects complete case data from private sector points-of-care. Between 2016 and 2019, the GMS Elimination of Malaria through Surveillance program supported national malaria programs in Cambodia, Lao PDR, Myanmar, and Vietnam to execute elimination strategies by engaging the private sector in malaria case management, generating private sector case data, and integrating these data into national surveillance systems. The project enrolled 21,903 private sector outlets, covering between 52% and 80% of the private sector in targeted geographies, which were trained and equipped to perform rapid diagnostic tests (RDTs) and report malaria case data. By 2019, the private providers enrolled in the program reported a total of 3,521,586 suspected cases and 96,400 confirmed malaria cases into national surveillance systems, representing 16% of the total reported caseload by these countries (Cambodia, 25%; Lao PDR, 5%; Myanmar, 12%; Vietnam, 8%). Results demonstrated that with comprehensive support, such as training, provision of free or subsidized RDTs, first-line treatments, and routine supportive supervision, private providers can provide quality malaria case management and achieve high reporting rates.

Characterizing mobility patterns of forest goers in southern Lao PDR using GPS loggers

BackgroundIn the Greater Mekong Subregion (GMS), forest-going populations are considered high-risk populations for malaria and are increasingly targeted by national control programmes’ elimination efforts. A better understanding of forest-going populations’ mobility patterns and risk associated with specific types of forest-going trips is necessary for countries in the GMS to achieve their objective of eliminating malaria by 2030.MethodsBetween March and November 2018, as part of a focal test and treat intervention (FTAT), 2,904 forest-goers were recruited in southern Lao PDR. A subset of forest-goers carried an “i-Got-U” GPS logger for roughly 2 months, configured to collect GPS coordinates every 15 to 30 min. The utilization distribution (UD) surface around each GPS trajectory was used to extract trips to the forest and forest-fringes. Trips with shared mobility characteristics in terms of duration, timing and forest penetration were identified by a hierarchical clustering algorithm. Then, clusters of trips with increased exposure to dominant malaria vectors in the region were further classified as high-risk. Finally, gradient boosting trees were used to assess which of the forest-goers’ socio-demographic and behavioural characteristics best predicted their likelihood to engage in such high-risk trips.ResultsA total of 122 forest-goers accepted carrying a GPS logger resulting in the collection of 803 trips to the forest or forest-fringes. Six clusters of trips emerged, helping to classify 385 (48%) trips with increased exposure to malaria vectors based on high forest penetration and whether the trip happened overnight. Age, outdoor sleeping structures and number of children were the best predictors of forest-goers’ probability of engaging in high-risk trips. The probability of engaging in high-risk trips was high (~ 33%) in all strata of the forest-going population.ConclusionThis study characterized the heterogeneity within the mobility patterns of forest-goers and attempted to further segment their role in malaria transmission in southern Lao People’s Democratic Republic (PDR). National control programmes across the region can leverage these results to tailor their interventions and messaging to high-risk populations and accelerate malaria elimination.

Spatio-temporal trends of malaria incidence from 2011 to 2017 and environmental predictors of malaria transmission in Myanmar

BackgroundMyanmar bears the heaviest malaria burden in the Greater Mekong Subregion (GMS). This study assessed the spatio-temporal dynamics and environmental predictors of Plasmodium falciparum and Plasmodium vivax malaria in Myanmar.MethodsMonthly reports of malaria cases at primary health centers during 2011–2017 were analyzed to describe malaria distribution across Myanmar at the township and state/region levels by spatial autocorrelation (Moran index) and spatio-temporal clustering. Negative binomial generalized additive models identified environmental predictors for falciparum and vivax malaria, respectively.ResultsFrom 2011 to 2017, there was an apparent reduction in malaria incidence in Myanmar. Malaria incidence peaked in June each year. There were significant spatial autocorrelation and clustering with extreme spatial heterogeneity in malaria cases and test positivity across the nation (P < 0.05). Areas with higher malaria incidence were concentrated along international borders. Primary clusters of P. falciparum persisted in western townships, while clusters of P. vivax shifted geographically over the study period. The primary cluster was detected from January 2011 to December 2013 and covered two states (Sagaing and Kachin). Annual malaria incidence was highest in townships with a mean elevation of 500‒600 m and a high variance in elevation (states with both high and low elevation). There was an apparent linear relationship between the mean normalized difference vegetative index and annual P. falciparum incidence (P < 0.05).ConclusionThe decreasing trends reflect the significant achievement of malaria control efforts in Myanmar. Prioritizing the allocation of resources to high-risk areas identified in this study can achieve effective disease control.Graphical

E-COMMERCE LOGISTICS IN THE GREATER MEKONG SUBREGION

The article explores the development of e-commerce logistics in the Greater Mekong Subregion as an example of digital transformation of economic and commercial activity in Southeast Asia. On reviewing the present state and the dynamics of e-commerce-related processes in Southeast Asia, the paper points out salient features of regional economic growth initiatives in synergy with the priorities of the ASEAN Economic Community (AEC) 2025. The substantial and the institutional dimension of the Greater Mekong Subregion (GMS) are discussed in detail. The paper finally turns to analyzing the GMS transport and logistics component in connection with e-commerce practices across the GMS area. The article does not aim to discuss the e-commerce and the economic corridors of the GMS apart from each other, which has been done by other researchers. Instead, the analytical focus of the paper, namely, a synergy between e-commerce, transport and logistics exemplified by the GMS cooperation, accounts for its academic novelty. The author argues that owing to the resources and assets that move beyond digitalization per se, China is likely to be the key beneficiary of the current demand for synergizing e-commerce with transport and logistics transnational infrastructure shared by Southeast Asia. Although this conclusion confirms earlier assessments, the GMS e-commerce logistics example convincingly demonstrates that Southeast Asia increasingly becomes a PRC-oriented area of economic and commercial activity.

The state and prospects of the development of the Mekong problem

The problem of water resources in international relations is one of the most discussed since the second half of the last century. Since the mid-1960s, water consumption in the world has more than doubled and continues to grow. This makes fresh water one of the most important factors influencing the international and domestic political situation. In the Greater Mekong subregion, this problem is already one of the main ones. The main reasons for this are rapid economic and demographic growth, as well as changing climatic conditions. The situation is complicated by the geopolitical significance of the region, which makes it a place of struggle for influence from global and regional players. The paper notes the role of the Mekong River in the economy of the countries of the subregion, because the contradictions between them are the main cause of international processes related to the river. The author also noted the influence on the situation from the leading world powers and the possibility of smoothing the problem from Russia.

Survey of malaria vectors on the Cambodia, Thailand and China-Laos Borders

BackgroundAnopheles maculatus, Anopheles minimus and Anopheles dirus are the major vectors of malaria transmission in the Greater Mekong Subregion (GMS). The malaria burden in this region has decreased significantly in recent years as all GMS countries progress towards malaria elimination. It is necessary to investigate the Anopheles diversity and abundance status and assess the Plasmodium infection rates to understand the malaria transmission potential of these vector species in GMS countries to guide the development of up-to-date vector control strategies and interventions.MethodsA survey of mosquitoes was conducted in Stung Treng, Sainyabuli and Phongsaly Provinces on the Cambodia-Laos, Thailand-Laos and China-Laos borders, respectively. Mosquito collection was done by overnight trapping at sentinel sites in each province. After morphological identification, the 18S rRNA-based nested-PCR was performed to detect malaria parasites in the captured Anopheles mosquitoes.ResultsA total of 18 965 mosquitoes comprising of 35 species of 2 subgenera (Subgenus Anopheles and Subgenus Cellia) and 4 tribes (Tribes Culicini, Aedini, Armigerini and Mansoniini) were captured. Tribe Culicini accounted for 85.66% of captures, followed by Subgenus Anopheles (8.15%). Anopheles sinensis dominated the Subgenus Anopheles by 99.81%. Plasmodium-infection was found in 25 out of the 1 683 individual or pooled samples of Anopheles. Among the 25 positive samples, 19, 5 and 1 were collected from Loum, Pangkhom and Siem Pang village, respectively. Eight Anopheles species were found infected with Plasmodium, i.e., An. sinensis, Anopheles kochi, Anopheles vagus, An. minimus, Anopheles annularis, Anopheles philippinensis, Anopheles tessellatus and An. dirus. The infection rates of Plasmodium falciparum, Plasmodium vivax and mixture of Plasmodium parasite species were 0.12% (2/1 683), 1.31% (22/1 683) and 0.06% (1/1 683), respectively.ConclusionsOverall, this survey re-confirmed that multiple Anopheles species carry malaria parasites in the international border areas of the GMS countries. Anopheles sinensis dominated the Anopheles collections and as carriers of malaria parasites, therefore may play a significant role in malaria transmission. More extensive investigations of malaria vectors are required to reveal the detailed vector biology, ecology, behaviour, and genetics in GMS regions in order to assist with the planning and implementation of improved malaria control strategies.Graphical

Different In Vitro Drug Susceptibility Profile of Plasmodium falciparum Isolates from Two Adjacent Areas of Northeast Myanmar and Molecular Markers for Drug Resistance.

The Greater Mekong Subregion (GMS) is the epicenter of antimalarial drug resistance. We determined in vitro susceptibilities to 11 drugs of culture-adapted Plasmodium falciparum isolates from adjacent areas (Laiza and Muse) along the China−Myanmar border. Parasites from this region were highly resistant to chloroquine and pyrimethamine but relatively sensitive to other antimalarial drugs. Consistently, the Dd2-like pfcrt mutations were fixed or almost fixed in both parasite populations, and new mutations mediating piperaquine resistance were not identified. Similarly, several mutations related to pfdhfr and pfdhps were also highly prevalent. Despite their geographical proximity, malaria parasites from Laiza showed significantly higher in vitro resistance to artemisinin derivatives, naphthoquine, pyronaridine, lumefantrine, and pyrimethamine than parasites from Muse. Likewise, the pfdhfr N51I, pfdhps A581G, pfmrp1 H785N, and pfk13 F446I mutations were significantly more frequent in Laiza than in Muse (p < 0.05). For the pfmdr1 mutations, Y184F was found only in Laiza (70%), whereas F1226Y was identified only in Muse (31.8%). Parasite isolates from Laiza showed a median RSA value of 5.0%, significantly higher than the 2.4% in Muse. Altogether, P. falciparum parasite populations from neighboring regions in the GMS may diverge substantially in their resistance to several antimalarial drugs. This information about different parasite populations will guide antimalarial treatment policies to effectively manage drug resistance during malaria elimination.

Dinuclear and mononuclear metal(II) polypyridyl complexes against drug-sensitive and drug-resistant Plasmodium falciparum and their mode of action

BackgroundMalaria remains one of the most virulent and deadliest parasitic disease in the world, particularly in Africa and Southeast Asia. Widespread occurrence of artemisinin-resistant Plasmodium falciparum strains from the Greater Mekong Subregion is alarming. This hinders the national economies, as well as being a major drawback in the effective control and elimination of malaria worldwide. Clearly, an effective anti-malarial drug is urgently needed.MethodsThe dinuclear and mononuclear copper(II) and zinc(II) complexes were synthesized in ethanolic solution and characterized by various physical measurements (FTIR, CHN elemental analysis, solubility, ESI-MS, UV-Visible, conductivity and magnetic moment, and NMR). X-ray crystal structure of the dicopper(II) complex was determined. The in vitro haemolytic activities of these metal complexes were evaluated spectroscopically on B+ blood while the anti-malarial potency was performed in vitro on blood stage drug-sensitive Plasmodium falciparum 3D7 (Pf3D7) and artemisinin-resistant Plasmodium falciparum IPC5202 (Pf5202) with fluorescence dye. Mode of action of metal complexes were conducted to determine the formation of reactive oxygen species using PNDA and DCFH-DA dyes, JC-1 depolarization of mitochondrial membrane potential, malarial 20S proteasome inhibition with parasite lysate, and morphological studies using Giemsa and Hoechst stains.ResultsCopper(II) complexes showed anti-malarial potency against both Pf3D7 and Pf5202 in sub-micromolar to micromolar range. The zinc(II) complexes were effective against Pf3D7 with excellent therapeutic index but encountered total resistance against Pf5202. Among the four, the dinuclear copper(II) complex was the most potent against both strains. The zinc(II) complexes caused no haemolysis of RBC while copper(II) complexes induced increased haemolysis with increasing concentration. Further mechanistic studies of both copper(II) complexes on both Pf3D7 and Pf5202 strains showed induction of ROS, 20S malarial proteasome inhibition, loss of mitochondrial membrane potential and morphological features indicative of apoptosis.ConclusionThe dinuclear [Cu(phen)-4,4′-bipy-Cu(phen)](NO3)4 is highly potent and can overcome the total drug-resistance of Pf5202 towards chloroquine and artemisinin. The other three copper(II) and zinc(II) complexes were only effective towards the drug-sensitive Pf3D7, with the latter causing no haemolysis of RBC. Their mode of action involves multiple targets.Graphical

Regimes of Extreme Permission in Southeast Asia: Theorizing State-Corporate Crime in the Global South

AbstractCorporations’ profit-making objectives are a central force guiding development strategies in the Global South but contradictorily can be blamed for a range of social and environmental harms. This article brings a state-corporate crime lens to bear on the economic and political processes that shape Global South-located commodity production. It seeks to understand the functioning of neo-imperialist profiteering through elaborating the concept of regimes of extreme permission, described as modalities of ‘intense’ accumulation, defined by weaker or unstable forms of hegemony consolidation, illegal/illicit practices, state-sanctioned violence and various socio-environmental degradations. Through analyses of two regimes of extreme permission in the SE Asian context—Indonesian palm oil plantations and Export Processing Zones for garment production in the Greater Mekong Subregion—the paper describes the role of states and corporations in constructing the repressive socio-political space required for neo-colonial corporate accumulation. We contribute to ‘Southernizing’ criminology by re-articulating state-corporate crime theory within imperialist contexts. It also shows that neo-colonialism can be understood as the de-regulation of corporate accumulation.

Trends in Forest Greening and Its Spatial Correlation with Bioclimatic and Environmental Factors in the Greater Mekong Subregion from 2001 to 2020

Understanding trends of vegetation evolution and its spatial characteristics is critical for sustainable social development in the Greater Mekong Subregion (GMS), which is densely populated and still has uneven economic development. Through Theil–Sen/Mann–Kendall tests, polynomial regression and bivariate local autocorrelation analyses, we investigated vegetation greening trends and their spatial correlation with bioclimatic and environmental variables. The study yielded the following results: (1) Land cover in the GMS has changed significantly over the last 20 years. Conversion between forest and grassland was the main type of change. (2) The upward trend in the forest enhanced vegetation index (EVI) significantly exceeded the downward trend in countries over 20 years. In GMS, the spatial variation in forest trend slope values ranged from −0.0297 a−1 to 0.0152 a−1. (3) Anthropogenic activities have played an important role in forest greening; planted, plantation and oil palm forests exhibit the largest contributions to greening. (4) Changes in forest EVI were most spatially correlated with radiation (12.19% for surface net solar radiation and 12.14% for surface solar radiation downwards) and least spatially correlated with seasonality precipitation (8.33%) and mean annual temperature (8.19%). The results of the analysis of EVI trends in vegetation and their spatial correlation with bioclimatic and environmental variables can provide a reference for strategies aimed for protecting the vegetation ecology.

Novel Species and Records of Dictyosporiaceae from Freshwater Habitats in China and Thailand.

China and Thailand are rich in fungal diversity with abundant freshwater resources that are favorable for numerous fungal encounters. Resulting from this, the majority of the Dictyosporiaceae species reported were from these two countries. During the investigation on the diversity of lignicolous freshwater fungi in the Greater Mekong Subregion, eleven collections of cheirosporous species on submerged wood were collected from lentic and lotic habitats in China and Thailand. Phylogenetic analysis that combined nuclear small-subunit ribosomal RNA (SSU), internal transcribed spacer region (ITS), nuclear large subunit ribosomal RNA (LSU) and translation elongation factor 1α (tef 1-α) loci revealed six new species: Dictyocheirospora chiangmaiensis, D. multiappendiculata, D. suae, Digitodesmium aquaticum, Vikalpa grandispora and V. sphaerica. In addition, four known species were also identified and reported based on morphological and phylogenetic evidence. The detailed descriptions and illustrations of these taxa are provided with an updated phylogenetic tree of Dictyosporiaceae.