OsαCA1 Affects Photosynthesis, Yield Potential, and Water Use Efficiency in Rice.

Plant growth and crop yield are essentially determined by photosynthesis when considering carbon dioxide (CO2) availability. CO2 diffusion inside a leaf is one of the factors that dictate the CO2 concentrations in chloroplasts. Carbonic anhydrases (CAs) are zinc-containing enzymes that interconvert CO2 and bicarbonate ions (HCO3-), which, consequently, affect CO2 diffusion and thus play a fundamental role in all photosynthetic organisms. Recently, the great progress in the research in this field has immensely contributed to our understanding of the function of the ß-type CAs; however, the analysis of α-type CAs in plants is still in its infancy. In this study, we identified and characterized the OsαCA1 gene in rice via the analysis of OsαCAs expression in flag leaves and the subcellular localization of its encoding protein. OsαCA1 encodes an α-type CA, whose protein is located in chloroplasts with a high abundance in photosynthetic tissues, including flag leaves, mature leaves, and panicles. OsαCA1 deficiency caused a significant reduction in assimilation rate, biomass accumulation, and grain yield. The growth and photosynthetic defects of the OsαCA1 mutant were attributable to the restricted CO2 supply at the chloroplast carboxylation sites, which could be partially rescued by the application of an elevated concentration of CO2 but not that of HCO3-. Furthermore, we have provided evidence that OsαCA1 positively regulates water use efficiency (WUE) in rice. In summary, our results reveal that the function of OsαCA1 is integral to rice photosynthesis and yield potential, underscoring the importance of α-type CAs in determining plant physiology and crop yield and providing genetic resources and new ideas for breeding high-yielding rice varieties.

Genome-Wide Identification and Expression Pattern Analysis of Dirigent Members in the Genus Oryza.

Dirigent (DIR) members have been shown to play essential roles in plant growth, development and adaptation to environmental changes. However, to date, there has been no systematic analysis of the DIR members in the genus Oryza. Here, 420 genes were identified from nine rice species to have the conserved DIR domain. Importantly, the cultivated rice species Oryza sativa has more DIR family members than the wild rice species. DIR proteins in rice could be classified into six subfamilies based on phylogeny analysis. Gene duplication event analysis suggests that whole genome/segmental duplication and tandem duplication are the primary drivers for DIR genes' evolution in Oryza, while tandem duplication is the main mechanism of gene family expansion in the DIR-b/d and DIR-c subfamilies. Analysis of the RNA sequencing data indicates that OsjDIR genes respond to a wide range of environmental factors, and most OsjDIR genes have a high expression level in roots. Qualitative reverse transcription PCR assays confirmed the responsiveness of OsjDIR genes to the undersupply of mineral elements, the excess of heavy metals and the infection of Rhizoctonia solani. Furthermore, there exist extensive interactions between DIR family members. Taken together, our results shed light on and provide a research foundation for the further exploration of DIR genes in rice.

Countering elevated CO2 induced Fe and Zn reduction in Arabidopsis seeds.

Growth at increased concentrations of CO2 induces a reduction in seed zinc (Zn) and iron (Fe). Using Arabidopsis thaliana, we investigated whether this could be mitigated by reducing the elevated CO2 -induced decrease in transpiration. We used an infrared imaging-based screen to isolate mutants in At1g08080 that encodes ALPHA CARBONIC ANHYDRASE 7 (ACA7). aca7 mutant alleles display wild-type (WT) responses to abscisic acid (ABA) and light but are compromised in their response to elevated CO2 . ACA7 is expressed in guard cells. When aca7 mutants are grown at 1000 ppm CO2 they exhibit higher transpiration and higher seed Fe and Zn content than WT grown under the same conditions. Our data show that by increasing transpiration it is possible to partially mitigate the reduction in seed Fe and Zn content when Arabidopsis is grown at elevated CO2 .

Green dual-template synthesis of AgPd core-shell nanoparticles with enhanced electrocatalytic activity.

A key challenge in developing an ethanol oxidation reaction is nontoxic fabrication of highly active stable and low-cost catalysts. Here we design a green synthetic strategy of AgPd bimetallic nanosphere by a dual-template cascade method. The Pd nanoshell is firstly prepared using Vapreotide acetate as a primary template, and then the Ag nanoshell acts as a secondary template for the distribution of AgPd alloy nanoparticles. The AgPd nanoparticles have core-shell structures and various sizes, and their shell thicknesses are tuned by controlling the amount of PdCl2. The six different samples are prepared, named AgPd-1, AgPd-2, AgPd-3, AgPd-4, AgPd-5, and AgPd-6, respectively. The mass current density of AgPd-5, is higher 3.87 times that of commercial Pd/C, and exhibits the best ethanol oxidation reaction activity and long-term stability. The main reasons are that the AgPd-5 possessed excellent specific surface area due to their rough structure, and Ag can remove more CO-like species. This is the first time a Vapreotide acetate/Ag-template method has been used to synthesize a AgPd core-shell structure, which would have broad application prospects for direct ethanol fuel cells.

A universal nanoreactor triggering butterfly effect for encouraging Fenton/Fenton-like reactions and chemodynamic therapy.

Fenton/Fenton-like reaction induced chemical dynamic therapy (CDT) has been widely recognized in tumor therapy. Due to the low efficiency of conversion from high-valent metal ions (M(n+1)+) to low-valent ions (Mn+) in the Fenton/Fenton-like catalytic process, enhancing the conversion efficiency safely and effectively would create a great opportunity for the clinical application of CDT. In the study, a universal nanoreactor (NR) consisting of liposome (Lip), tumor cell membrane (CM), and bis(2,4,5-trichloro-6-carboxyphenyl) oxalate (CPPO) is developed to tackle this challenge. The CPPO was first discovered to decompose under weak acidity and H2O2 conditions to generate carboxylic acids (R'COOH) and alcohols (R'OH) with reducibility, which will reduce M(n+1)+ to Mn+ and magnify the effect of CDT. Furthermore, glucose oxidase (GOx) was introduced to decompose glucose in tumor and generate H2O2 and glucose acid, which promote the degradation of CPPO, further strengthening the efficiency of CDT, leading to a butterfly effect. This demonstrated that the butterfly effect triggered by NR and GOx encourages Fenton/Fenton-like reactions of Fe3O4 and MoS2, thereby enhancing the tumor inhibition effect. The strategy of combining GOx and CPPO to strengthen the Fenton/Fenton-like reaction is a universal strategy, which provides a new and interesting perspective for CPPO in the application of CDT, reflecting the exquisite integration of Fenton chemistry and catalytic medicine.

Nanomedicine alleviates doxorubicin-induced cardiotoxicity and enhances chemotherapy synergistic chemodynamic therapy.

Doxorubicin (DOX) is widely used in clinic as a broad-spectrum chemotherapy drug, which can enhance the efficacy of chemodynamic therapy (CDT) by interfering tumor-related metabolize to increase H2O2 content. However, DOX can induce serious cardiomyopathy (DIC) due to its oxidative stress in cardiomyocytes. Eliminating oxidative stress would create a significant opportunity for the clinical application of DOX combined with CDT. To address this issue, we introduced sodium ascorbate (AscNa), the main reason is that AscNa can be catalyzed to produce H2O2 by the abundant Fe3+ in the tumor site, thereby enhancing CDT. While the content of Fe3+ in heart tissue is relatively low, so the oxidation of AscNa had tumor specificity. Meanwhile, due to its inherent reducing properties, AscNa could also eliminate the oxidative stress generated by DOX, preventing cardiotoxicity. Due to the differences between myocardial tissue and tumor microenvironment, a novel nanomedicine was designed. MoS2 was employed as a carrier and CDT catalyst, loaded with DOX and AscNa, coating with homologous tumor cell membrane to construct an acid-responsive nanomedicine MoS2-DOX/AscNa@M (MDA@M). In tumor cells, AscNa enhances the synergistic therapy of DOX and MoS2. In cardiomyocytes, AscNa could effectively reduce the cardiomyopathy induced by DOX. Overall, this study enhanced the clinical potential of chemotherapy synergistic CDT.

Natural MOF-Like Photocatalytic Nanozymes Alleviate Tumor Pressure for Enhanced Nanodrug Penetration.

In oncological nanomedicine, overcoming the dual-phase high interstitial pressure in the tumor microenvironment is pivotal for enhancing the penetration and efficacy of nanotherapeutics. The elevated tumor interstitial solid pressure (TISP) is largely attributed to the overaccumulation of collagen in the extracellular matrix, while the increased tumor interstitial fluid pressure (TIFP) stems from the accumulation of fluid due to the aberrant vascular architecture. In this context, metal-organic frameworks (MOFs) with catalytic efficiency have shown potential in degrading tumor interstitial components, thereby reducing interstitial pressure. However, the potential biotoxicity of the organic components of MOFs limits their clinical translation. To circumvent this, a MOF-like photocatalytic nanozyme, RPC@M, using naturally derived cobalt phytate (CoPA) and resveratrol (Res) is developed. This nanozyme not only facilitates the decomposition of water in the tumor interstitium under photoactivation to reduce TIFP, but also generates an abundance of reactive oxygen species through its peroxidase-like activity to exert cytotoxic effects on tumor cells. Moreover, Res contributes to the reduction of collagen deposition, thereby lowering TISP. The concurrent diminution of both TISP and TIFP by RPC@M leads to enhanced tumor penetration and potent antitumor activity, presenting an innovative approach in constructing tumor therapeutic nanozymes from natural products.

Effects of Leea indica leaf extracts and its phytoconstituents on natural killer cell-mediated cytotoxicity in human ovarian cancer.

BACKGROUND: The rich biodiversity of medicinal plants and their importance as sources of novel therapeutics and lead compounds warrant further research. Despite advances in debulking surgery and chemotherapy, the risks of recurrence of ovarian cancer and resistance to therapy are significant and the clinical outcomes of ovarian cancer remain poor or even incurable. OBJECTIVE: This study aims to investigate the effects of leaf extracts from a medicinal plant Leea indica and its selected phytoconstituents on human ovarian cancer cells and in combination with oxaliplatin and natural killer (NK) cells. METHODS: Fresh, healthy leaves of L. indica were harvested and extracted in 70% methanol by maceration. The crude extract was partitioned with n-hexane, dichloromethane and ethyl acetate. Selected extracts and compounds were analyzed for their effects on cell viability of human ovarian cancer cells, NK cell cytotoxicity, and stress ligands expression for NK cell receptors. They were also evaluated for their effects on TNF-α and IL-1ß production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages. RESULTS: Leaf extracts of L. indica increased the susceptibility of human ovarian tumor cells to NK cell-mediated cytotoxicity. Treatment of cancer cells with methyl gallate but not gallic acid upregulated the expression of stress ligands. Tumor cells pretreated with combination of methyl gallate and low concentration of oxaliplatin displayed increased levels of stress ligands expression and concomitantly enhanced susceptibility to NK cell-mediated cytolysis. Further, NK cells completely abrogated the growth of methyl gallate-pretreated ovarian cancer cells. The leaf extracts suppressed TNF-α and IL-1ß production in human U937 macrophages. Methyl gallate was more potent than gallic acid in down-regulating these cytokine levels. CONCLUSIONS: We demonstrated for the first time that leaf extracts of L. indica and its phytoconstituent methyl gallate enhanced the susceptibility of ovarian tumor cells to NK cell cytolysis. These results suggest that the combined effect of methyl gallate, oxaliplatin and NK cells in ovarian cancer cells warrants further investigation, for example for refractory ovarian cancer. Our work is a step towards better scientific understanding of the traditional anticancer use of L. indica.

MoS2 nanoflower-mediated enhanced intratumoral penetration and piezoelectric catalytic therapy.

The absence of lymphatic vessels in tumors leads to the retention of interstitial fluid, and the formation of an inverse pressure difference between the tumor and blood vessels hinders drug delivery deep into the tumor, which leads to tumor recurrence and metastasis. Therefore, we designed a novel strategy to downregulate tumor interstitial fluid pressure (TIFP) by water splitting in the tumor interstitium based on piezoelectric catalysis nanomedicine. First, the chemotherapeutic drug doxorubicin (DOX) was loaded on the piezoelectric catalytic material MoS2 and then encapsulated with tumor cell membrane (CM) to obtain MD@C. MD@C could not only target the tumor through homologous targeting but, more importantly, also triggered piezoelectric catalytic water splitting under ultrasound (US) stimulation; as a result, the TIFPs of U14 and PAN02 tumor-bearing mice were reduced to 57.14% and 45.5%, respectively, and the tumor inhibition rates of MD@C were 96.75% and 99.21%, which increased the perfusion of blood-derived drugs in the tumors. Moreover, the hydroxyl radicals generated by piezoelectric catalysis could effectively inhibit the growth of tumors in combination with DOX. Consequently, the piezoelectric catalytic water splitting strategy of MD@C can enhance drug delivery, providing a new universal platform for the treatment of solid malignant tumors.

Human Mobility to Parks Under the COVID-19 Pandemic and Wildfire Seasons in the Western and Central United States.

In 2020, people's health suffered a great crisis under the dual effects of the COVID-19 pandemic and the extensive, severe wildfires in the western and central United States. Parks, including city, national, and cultural parks, offer a unique opportunity for people to maintain their recreation behaviors following the social distancing protocols during the pandemic. However, massive forest wildfires in western and central US, producing harmful toxic gases and smoke, pose significant threats to human health and affect their recreation behaviors and mobility to parks. In this study, we employed the geographically and temporally weighted regression (GTWR) Models to investigate how COVID-19 and wildfires jointly shaped human mobility to parks, regarding the number of visits per capita, dwell time, and travel distance to parks, during June - September 2020. We detected strong correlations between visitations and COVID-19 incidence in southern Montana, western Wyoming, Colorado, and Utah before August. However, the pattern was weakened over time, indicating the decreasing trend of the degree of concern regarding the pandemic. Moreover, more park visits and lower dwell time were found in parks further away from wildfires and less air pollution in Washington, Oregon, California, Colorado, and New Mexico, during the wildfire season, suggesting the potential avoidance of wildfires when visiting parks. This study provides important insights on people's responses in recreation and social behaviors when facing multiple severe crises that impact their health and wellbeing, which could support the preparation and mitigation of the health impacts from future pandemics and natural hazards.

Satellite-detected ammonia changes in the United States: Natural or anthropogenic impacts.

Ammonia (NH3) is the most abundant alkaline component and can react with atmospheric acidic species to form aerosols that can lead to numerous environmental and health issues. Increasing atmospheric NH3 over agricultural regions in the US has been documented. However, spatiotemporal changes of NH3 concentrations over the entire US are still not thoroughly understood, and the factors that drive these changes remain unknown. Herein, we applied the Atmospheric Infrared Sounder (AIRS) monthly NH3 dataset to explore spatiotemporal changes in atmospheric NH3 and the empirical relationships with synthetic N fertilizer application, livestock manure production, and climate factors across the entire US at both regional and pixel levels from 2002 to 2016. We found that, in addition to the US Midwest, the Mid-South and Western regions also experienced striking increases in NH3 concentrations. NH3 released from livestock manure during warmer winters contributed to increased annual NH3 concentrations in the Western US. The influence of temperature on temporal evolution of NH3 concentrations was associated with synthetic N fertilizer use in the Northern Great Plains. With a strong positive impact of temperature on NH3 concentrations in the US Midwest, this region could possibly become an atmospheric NH3 hotspot in the context of future warming. Our study provides an essential scientific basis for US policy makers in developing mitigation strategies for agricultural NH3 emissions under future climate change scenarios.

Sequential Intra-Intercellular Delivery of Nanomedicine for Deep Drug-Resistant Solid Tumor Penetration.

Cells in the center of solid tumors have always been an abyss untouched by treatments because of their deep location and increased drug resistance. Herein, we designed a rational strategy for sequential intra-intercellular delivery of nanomedicine to deep sites of drug-resistant solid tumors. In our formulation, dopamine and hemoglobin were polymerized to form a smart nanocarrier (PDA/Hb). Subsequently, the doxorubicin and nitric oxide donor were connected on the surface of PDA/Hb to obtain D/N-PDA/Hb. Ultimately, the hyaluronic acid was combined with D/N-PDA/Hb to form D/N-PDA/Hb@HA. Concretely, acidic and neutral environments of tumor cells were treated as a switch to turn on or off the drug release of a nanodrug. Meanwhile, the generation of nitric oxide in situ was exploited to favor the lysosomal escape of nanocarriers and overcome the drug resistance of deep solid tumor cells. The results indicated that the nanodrug based on sequential intra-intercellular delivery showed exciting penetration efficiency and resistance reversal of solid tumors. Conventional nanodrug delivery was highly dependent on the enhanced permeability and retention (EPR) effect and limited by tumorous interstitial fluid pressure. Plenty of drugs stayed on the surface of solid tumors, and the infiltrated drugs were inefficient due to strict resistance. To conquer this dilemma, this work proposed a new mechanism reversing the EPR effect for drug delivery, leading to better penetration and resistance reversal of solid tumors.

Seedless synthetic branched gold nanoshells for chemo-thermal antitumor therapy.

Gold nanomaterials (GNMs) are used in photothermal therapy due to their superior optical properties and excellent biocompatibility. However, the complex preparation process involving seed-mediated growth limits further clinical applications of GNMs. Herein, a novel one-pot approach to rapidly prepare liposome-based branched gold nanoshells (BGNS) as an antitumor drug nanocarrier is reported. This efficient seedless synthesis realized tunable absorption peaks of BGNS through controlling the concentration of the Au precursor solution, obtaining high absorbance in the near-infrared (NIR) window to achieve a superior photothermal effect. Hyperthermia during NIR laser irradiation can ablate the tumor and trigger drug release to achieve combined treatment. After laser irradiation, the nanocarriers disintegrated into individual gold nanoparticles (size: about 8 nm), which can be metabolized by the kidneys. Cell experiments in vitro and experiments involving mice with tumors have confirmed that the nanodrugs have strong antitumor effects. Such a flexible method provides a universal approach for rapidly preparing liposome-based gold nanoshells, which have the potential for large-scale preparation for further clinical applications.

Sensitive measurement of tumor markers somatostatin receptors using an octreotide-directed Pt nano-flakes driven electrochemical sensor.

Tumor markers play an important role in the early diagnosis and therapeutic effect monitoring of tumors. An electrochemical biosensor was developed based on multi-branched gold nanoshells (BGSs) and octreotide (OCT) functionalized Pt nano-flakes (PtNFs) modified electrodes, which was used for detection of tumor-specific markers to evaluate tumor cells. Sandwich-type nano-hybrid materials were prepared by layer-by-layer modification. First, reduced graphene oxide (RGO) and BGSs were modified as electronic materials onto glassy carbon electrodes (GCE). This modified electrode has strong electron transfer capability and large electrode surface area. The OCT was then anchored to the surface of BGSs to sensitively detect Somatostatin receptors (SSTRs) on the surface of HeLa cells. In addition, PtNFs were synthesized using a dual-template method, and OCT template on the surface of PtNFs, as an adsorption bioprobe, was used to reduce the H2O2 and amplify the electrochemical signal of biosensor. The proposed biosensor can be applied to the quantitative broad linear range of HeLa cells covering from 10 to 1 × 106 cells mL-1 (R2 = 0.9998) and the limit of detection (LOD) was 2 cells mL-1. The experimental results also show that the sensor has good stability, biocompatibility and high selectivity, which has great potential for clinical application.

Climate, forest growing season, and evapotranspiration changes in the central Appalachian Mountains, USA.

We analyzed trends in climatologic, hydrologic, and growing season length variables, identified the important variables effecting growing season length changes, and evaluated the influence of a lengthened growing season on increasing evapotranspiration trends for the central Appalachian Mountains region of the United States. We generated three growing season length variables using remotely sensed GIMMS NDVI3g data, two variables from measured streamflow, and 13 climate parameters from gridded datasets. We included various climate, hydrology, and phenology explanatory variables in two applications of Principle Components Analysis to reduce dimensionality, then utilized the final variables in two Linear Mixed Effects models to evaluate the role of climate on growing season length and evapotranspiration. The results showed that growing season length has increased, on average, by ~22 days and evapotranspiration has increased up to ~12 mm throughout the region. The results also suggest that a suite of climatic variables including temperature, vapor pressure deficit, wind, and humidity are important in growing season length change. The climatic variables work synergistically to produce greater evaporative demand and atmospheric humidity, which is theoretically consistent with intensification of the water cycle and the Clausius-Clapeyron relation, which states that humidity increases nonlinearly by 7%/K. Optimization of the evapotranspiration model was increased by the inclusion of growing season length, suggesting that growing season length is partially responsible for variations in evapotranspiration over time. The results of this research imply that a longer growing season has the potential to increase forest water cycling and evaporative loss in temperate forests, which may lead to decreased freshwater provisioning from forests to downstream population centers. Additionally, results from this study provide important information for runoff and evapotranspiration modelling and forest water management under changing climate.

Near-Infrared Responsive Bimetallic Nanovesicles for Enhanced Synergistic Chemophotothermal Therapy.

Limited therapeutic effects and obvious side effects are two critical problems affecting tumor therapy. Herein, we designed an ingenious nanocarrier, platinum/gold bimetallic-nanoshell-coated triptolide liposomes (Pt@Au-TP-Lips), to achieve enhanced chemophotothermal therapy against cancer. Compared to conventional gold nanoflower structures, the platinum/gold bimetallic (Pt@Au) core-shells exhibited broader near-infrared (NIR) absorption due to the ultrastrong plasmonic coupling effect. With NIR light irradiation, the Pt@Au nanostructure could efficiently and sustainably convert light energy into substantial heat. The ultrahigh photothermal conversion efficiency (56.5%) of Pt@Au-TP-Lips was significantly higher than that of gold nanoflowers (35.7%). Specifically, hyperthermia could induce a phase change in the liposome membrane to accelerate the release of triptolide (TP); meanwhile, it could ablate tumor cells directly and facilitate the cellular uptake of drugs to enhance chemotherapy. More importantly, owing to the cooperation of TP and platinum, Pt@Au-TP-Lips exhibited significant tumor growth suppression with a high inhibitory rate of 90.7%, achieving superior chemophotothermal combination therapy. This work provides new insight into the development of a cooperative theranostic agent for oncotherapy.

Dual Stimuli-Responsive Peptide-Based Palladium Nano-Lychee Spheres for Synergistic Antitumor Therapy.

The application of peptide-based biomaterials in nanocarriers can effectively reduce toxicity and improve the biocompatibility. In our study, a dual stimuli-responsive peptide-based drug delivery system was designed and synthesized, which was nontoxic and achieved the chem-photothermal therapy synergistic effect. Lanreotide (Lan), a kind of somatostatin analogue, was used as internal template to prepared lychee-shaped palladium (Pd) nanoparticles (Lan-PdNPs). Glutathione (GSH) and doxorubicin (DOX) were combined on the surface of Lan-PdNPs to obtain the nanosystem of Lan-PdNPs@GSH/DOX. Based on the lychee-shaped structures, the system demonstrated higher photothermal conversion performance and photothermal stability. Under NIR laser irradiation, Lan-PdNPs@GSH/DOX could convert light energy to heat in effect and accelerate drug release. Moreover, in acidic conditions, the system also exhibited the pH-responsive drug release. Owing to the synergism, the antitumor effects of Lan-PdNPs@GSH/DOX in vitro and in vivo were superior, and the inhibition ratio was much higher than that of chemotherapy or photothermal therapy alone. The good biocompatibility and nontoxicity of the system also provide the possibility for serving as an antitumor drug candidate.

Enhancing Effects of Theanine Liposomes as Chemotherapeutic Agents for Tumor Therapy.

Chemotherapy is one of the most effective methods of treating tumors in clinical study currently, but drug side effects usually are unbearable to the patient, which also makes it difficult to continue chemotherapy. Enhanced drug efficacy and reduced drug side effects are the main strategies for tumor therapy. Herein, based on biochemical regulation, theanine liposomes were designed to adjuvant doxorubicin (DOX) therapy, which can reduce the adverse reactions and enhance the effect of DOX. Stigmasterol was applied instead of traditional cholesterol for reducing the risk of cardiovascular disease. The as-prepared theanine liposomes by two methods had optimal sizes (154.8 and 169.0 nm), which can effectively accumulate in tumor tissues. In vitro experiments demonstrated that the theanine liposomes had a good effect of sustaining drug release. Cell uptake indicated that the presence of theanine can effectively inhibit glutathione (GSH) levels in cells and increase the uptake of DOX. In tumor bearing mice experiments, the combination of the theanine liposomes and DOX showed a better tumor inhibitory effect with a smaller tumor volume (2.7 fold) compared with that of the free DOX group. Meanwhile, under the mediation of theanine, the amount of doxorubicin was greatly reduced to achieve the same therapeutic effect, and the side effects of the drug were largely inhibited. Therefore, theanine liposomes have great application potential in tumor chemotherapy.

Risk Assessment and Mapping of Hand, Foot, and Mouth Disease at the County Level in Mainland China Using Spatiotemporal Zero-Inflated Bayesian Hierarchical Models.

Hand, foot, and mouth disease (HFMD) is a worldwide infectious disease, prominent in China. China's HFMD data are sparse with a large number of observed zeros across locations and over time. However, no previous studies have considered such a zero-inflated problem on HFMD's spatiotemporal risk analysis and mapping, not to mention for the entire Mainland China at county level. Monthly county-level HFMD cases data combined with related climate and socioeconomic variables were collected. We developed four models, including spatiotemporal Poisson, negative binomial, zero-inflated Poisson (ZIP), and zero-inflated negative binomial (ZINB) models under the Bayesian hierarchical modeling framework to explore disease spatiotemporal patterns. The results showed that the spatiotemporal ZINB model performed best. Both climate and socioeconomic variables were identified as significant risk factors for increasing HFMD incidence. The relative risk (RR) of HFMD at the local scale showed nonlinear temporal trends and was considerably spatially clustered in Mainland China. The first complete county-level spatiotemporal relative risk maps of HFMD were generated by this study. The new findings provide great potential for national county-level HFMD prevention and control, and the improved spatiotemporal zero-inflated model offers new insights for epidemic data with the zero-inflated problem in environmental epidemiology and public health.

Effects of Temperature on Development and Voltinism of Chaetodactylus krombeini (Acari: Chaetodactylidae): Implications for Climate Change Impacts.

Temperature plays an important role in the growth and development of arthropods, and thus the current trend of climate change will alter their biology and species distribution. We used Chaetodactylus krombeini (Acari: Chaetodactylidae), a cleptoparasitic mite associated with Osmia bees (Hymenoptera: Megachilidae), as a model organism to investigate how temperature affects the development and voltinism of C. krombeini in the eastern United States. The effects of temperature on the stage-specific development of C. krombeini were determined at seven constant temperatures (16.1, 20.2, 24.1, 27.5, 30.0, 32.4 and 37.8°C). Parameters for stage-specific development, such as threshold temperatures and thermal constant, were determined by using empirical models. Results of this study showed that C. krombeini eggs developed successfully to adult at all temperatures tested except 37.8°C. The nonlinear and linear empirical models were applied to describe quantitatively the relationship between temperature and development of each C. krombeini stage. The nonlinear Lactin model estimated optimal temperatures as 31.4, 32.9, 32.6 and 32.5°C for egg, larva, nymph, and egg to adult, respectively. In the linear model, the lower threshold temperatures were estimated to be 9.9, 14.7, 13.0 and 12.4°C for egg, larva, nymph, and egg to adult, respectively. The thermal constant for each stage completion were 61.5, 28.1, 64.8 and 171.1 degree days for egg, larva, nymph, and egg to adult, respectively. Under the future climate scenarios, the number of generations (i.e., voltinism) would increase more likely by 1.5 to 2.0 times by the year of 2100 according to simulation. The findings herein firstly provided comprehensive data on thermal development of C. krombeini and implications for the management of C. krombeini populations under global warming were discussed. *Scientific Article No. 3278 of the West Virginia Agricultural and Forestry Experiment Station, Morgantown, West Virginia.