Adapting vector surveillance using Bayesian experimental design: An application to an ongoing tick monitoring program in the southeastern United States.

Maps of the distribution of medically-important ticks throughout the US remain lacking in spatial and temporal resolution in many areas, leading to holes in our understanding of where and when people are at risk of tick encounters, an important baseline for informing public health response. In this work, we demonstrate the use of Bayesian Experimental Design (BED) in planning spatiotemporal surveillance of disease vectors. We frame survey planning as an optimization problem with the objective of identifying a calendar of sampling locations that maximizes the expected information regarding some goal. Here we consider the goals of understanding associations between environmental factors and tick presence and minimizing uncertainty in high risk areas. We illustrate our proposed BED workflow using an ongoing tick surveillance study in South Carolina parks. Following a model comparison study based on two years of initial data, several techniques for finding optimal surveys were compared to random sampling. Two optimization algorithms found surveys better than all replications of random sampling, while a space-filling heuristic performed favorably as well. Further, optimal surveys of just 20 visits were more effective than repeating the schedule of 111 visits used in 2021. We conclude that BED shows promise as a flexible and rigorous means of survey design for vector control, and could help alleviate pressure on local agencies by limiting the resources necessary for accurate information on arthropod distributions. We have made the code for our BED workflow publicly available on Zenodo to help promote the application of these methods to future surveillance efforts.

The utility of a Bayesian predictive model to forecast neuroinvasive West Nile virus disease in the United States of America, 2022.

Arboviruses (arthropod-borne-viruses) are an emerging global health threat that are rapidly spreading as climate change, international business transport, and landscape fragmentation impact local ecologies. Since its initial detection in 1999, West Nile virus has shifted from being a novel to an established arbovirus in the United States of America. Subsequently, more than 25,000 cases of West Nile neuro-invasive disease have been diagnosed, cementing West Nile virus as an arbovirus of public health importance. Given its novelty in the United States of America, high-risk ecologies are largely underdefined making targeted population-level public health interventions challenging. Using the Centers for Disease Control and Prevention ArboNET neuroinvasive West Nile virus data from 2000-2021, this study aimed to predict neuroinvasive West Nile virus human cases at the county level for the contiguous USA using a spatio-temporal Bayesian negative binomial regression model. The model includes environmental, climatic, and demographic factors, as well as the distribution of host species. An integrated nested Laplace approximation approach was used to fit our model. To assess model prediction accuracy, annual counts were withheld, forecasted, and compared to observed values. The validated models were then fit to the entire dataset for 2022 predictions. This proof-of-concept mathematical, geospatial modelling approach has proven utility for national health agencies seeking to allocate funding and other resources for local vector control agencies tackling West Nile virus and other notifiable arboviral agents.

Spatiotemporal changes of aerosol optical depth and its response to urbanization: a case study of Jinan City, China, 2009-2018.

With the insidiously growing impact of urban development on the environment, the issue of air quality has attracted extensive attention nationally and globally. It is of great significance to study the influence of urbanization on air quality for the rational development of cities. MODIS-MAIAC (Moderate Resolution Imaging Spectroradiometer-Multi-Angle Implementation of Atmospheric Correction) Aerosol optical depth (AOD) product, DMSP/OLS (Defense Meteorological Satellite Program/Operational Linescan System) and NPP/VIIRS (Suomi National Polar-orbiting Partnership/Visible Infrared Imaging Radiometer Suite) night-light were used to explore the spatiotemporal variation and correlation between AOD and urbanization development before and after the promulgation of environmental governance policies in Jinan City from 2009 to 2018. Results show that (1) the spatial distribution of AOD in Jinan had the characteristics of high in the north and low in the south, high in the west and low in the east, and low in some parts of the central region; there was a significant seasonal variation in time, with the highest AOD in summer and the lowest in winter. During 2009-2013, the annual average variation of AOD increased by 20.6%, while during 2014-2018, it decreased by 35.3%; (2) The distribution of night-light in Jinan City has progressively expanded, mirroring the city's ongoing development. The spatial distribution of aerosols in urban areas was relatively low compared to the surrounding areas of the city. (3) From 2009 to 2013, there existed a significant positive correlation between the spatial and temporal distribution of AOD and night-light. However, from 2014 to 2018, with the implementation of environmental governance policies, this relationship shifted to a significant negative correlation between the spatial and temporal distribution of AOD and night-light. Through an analysis of the correlation between urban development and aerosol depth in Jinan City over the past decade, it can be concluded that urban development does not inevitably result in elevated AOD levels. Notably, the Jinan government has achieved remarkable results in controlling the atmospheric environment, as evidenced by recent years' improvements.

Environmental pollution and economic growth: Evidence of SO2 emissions and GDP in China.

This study explores the inherent linkage mechanism between environmental pollution and economic growth using a non-linear MS (M)-VAR (p) model. The results indicate that, first, the growth rates of China's gross domestic product (GDP) and SO2 emissions are in a state of significant inertia. Second, when the system was in a medium-growth regime, the growth rates of SO2 emissions and GDP had a positive correlation, characterized by lower probability and weaker durability. Third, when the system was in a high- or low-growth regime, their growth rates were negatively correlated, characterized by higher probability and stronger durability. Overall, economic growth increases environmental pollution emissions, which intensifies as well as inhibits economic growth. The correlation and sustainability of SO2 emissions and GDP are closely related to the regional status of the entire system. This study is helpful in analyzing the reasons for the nonlinear linkage mechanism between environmental pollution and economic growth.

Spatiotemporal assessment of potential drivers of salt marsh dieback in the North Inlet-Winyah Bay estuary, South Carolina (1990-2019).

Previous studies in the Gulf of Mexico and Atlantic states have suggested that a suite of possibly abiotic and biotic attributes is responsible for salt marsh dieback, e.g., drought, soil waterlogging, soil chemistry, top-down consumers control, etc. However, there are no conclusive answers in current literature explaining what led to marsh dieback in past decades, especially from the spatiotemporal perspective. Exploring all Landsat-retrieved marsh dieback events in 1990-2019, this research investigates the spatiotemporal relationships between the dieback series and the associated environmental variables in an intertidal marsh in South Carolina (SC). Based on our previous study, a series of marsh dieback events in the past 30 years were identified and dieback pixels in the estuary were extracted. Among these were the most severe marsh dieback events (1991, 1999, 2000, 2002, 2004, and 2013). Daily Evaporative Demand Drought Index (EDDI), daily precipitation data from Parameter Elevation Regressions on Independent Slopes Model (PRISM), and station-based water quality observations (dissolved oxygen, specific conductivity, salinity, turbidity, pH, and temperature) in the estuary were retrieved. Integrated with the proof-by-exhaustion method, statistical analysis showed marsh dieback were highly related to moisture imbalance in a period of 90 days before the dieback events. Respectively, pH for Clambank and Debidue Creek, salinity and turbidity for Thousand Acre were found to be the key water quality variables influencing marsh dieback besides drought. This study cogitates the environmental influence on coastal marsh dieback from a spatiotemporal perspective using a long-term satellite time series analysis. The findings could provide insights into marsh ecological resilience and facilitate coastal ecosystem management.

Cold exposure and capsaicin promote 1,2-dimethylhyrazine-induced colon carcinogenesis in rats correlates with extracellular matrix remodeling.

BACKGROUND: Extracellular matrix (ECM) remodeling and stiffening, which are correlated with tumor malignancy, drives tumor development. However, the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine (DMH)-induced colorectal cancer (CRC) imposed by cold and capsaicin exposure remains unclear. AIM: To explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC. METHODS: For histopathological analysis, the sections of colon tissues were stained with hematoxylin and eosin, Masson's trichrome, Picrosirius red, and Weigert's Resorcin-Fuchsin to observe the remodeling of collagen and elastin. Additionally, the protein expression level of type I collagen (COL I), type 3 collagen (COL III0, elastin, matrix metalloproteinase (MMP) 1, MMP2, MMP9, and tissue-specific matrix metalloproteinase 1 (TIMP1) was assessed by immunohistochemistry. The messenger RNA (mRNA) levels of COL I, COL III, elastin, and lysyl oxidase-like-2 (LOXL2) in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction. RESULTS: Although no differences were observed in the proportion of adenomas, a trend towards the increase of invasive tumors was observed in the cold and capsaicin group. The cold exposure group had a metastasis rate compared with the other groups. Additionally, abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group. Specifically, collagen quantitative analysis showed increased length, width, angle, and straightness compared with the DMH group. Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group. Cold exposure and capsaicin significantly increased the protein levels of COL I, elastin, and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group, while COL III did not show a significant difference. Furthermore, in immunohistochemical evaluations, MMP1, MMP2, MMP9, and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group. CONCLUSION: These results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue. Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue. The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.

Analysis of Colorectal Carcinogenesis Paradigm between Cold Constitution and Heat Constitution: Earlier ECM Collagen Deposition.

Colorectal cancer (CRC) is a common malignant tumor around the world. Studying the unique constitution of CRC patients is conducive to the application of personalized medical treatment for CRC. The most common types of constitution in CRC are cold and heat constitution. A previous study has suggested that the malignant progression in cold and heat constitution CRC are different; however, the mechanism remains unclear. The tumor microenvironment (TME) is likely to vary with each individual constitution, which may affect the tumor growth in different constitutions. The extracellular matrix (ECM), the most important component of TME, plays a critical role in disease progression and outcome in patients with CRC. Moreover, collagen, the major component of the ECM, determines the main functional characteristics of ECM and tissue fibrosis caused by collagen deposition, which is one of the signs of CRC malignant progression. This study aimed to explore the mechanisms leading to different colorectal carcinogenesis paradigms between the cold constitution and heat constitution within the context of ECM collagen deposition. We established the CRC rat models and enrolled 30 CRC patients with cold and heat constitution. The collagen-related parameters were detected by using Sirius red staining combined with polarized light microscope, and expressions of collagen (COL I and COL III) and lysyl oxidase (LOX and LOXL2) were determined using immunohistochemistry, while the mRNA levels of COL1A1, COL3A1, LOX, and LOXL2 were measured by qRT-PCR. We found that a higher degree of collagen deposition in the cold-constitution group. The results suggest cold and heat constitution may affect the colorectal carcinogenesis paradigm by influencing the early collagen deposition in colon tissue. The study may provide an effective idea for clinicians to improve the prognosis of CRC patients with different constitutions.

Effect of cold exposure and capsaicin on the expression of histone acetylation and Toll-like receptors in 1,2-dimethylhydrazine-induced colon carcinogenesis.

Previous studies have indicated that capsaicin-rich diet and cold weather have shown strong association with tumor incidence. Thus, we investigated the effects of capsaicin and cold exposure in 1,2-dimethylhydrazine (DMH)-induced colorectal cancer as well as the mechanisms underlying capsaicin and cold-induced CRC. Rats were randomly divided into four groups and received cold still water and capsaicin via intragastric gavage until the end of the experiment. The rat's body weight, thymus weight, and food intakes were assessed. Global levels of histone H3K9, H3K18, H3K27, and H4K16 acetylation and histone deacetylase (HDACs) in colon mucosa were assessed by western blot. Expression levels of Toll-like receptors 2 (TLR2) and Toll-like receptors 4 (TLR4) were measured by western blot and reverse-transcriptase quantitative polymerase chain reaction (qPCR). We found that cold and low-dose capsaicin increased tumor numbers and multiplicity, although there were no differences in tumor incidence. Additionally, rat exposure to cold water and capsaicin display further higher levels of histone H3 lysine 9 (H3K9AC), histone H3 lysine 18 (H3K18AC), histone H3 lysine 27 (H3K27AC), and HDACs compared with the DMH and normal rats. In contrast, a considerable decrease of histone H4 lysine 16 (H4K16AC) was detected in the colon mucosa. Cold and low-dose capsaicin exposure groups were also increased TLR2 and TLR4 protein levels and mRNA levels. These results suggest that chronic cold exposure and capsaicin at a low-dose intervention exacerbate ectopic expression of global histone acetylation and TLR level, which are crucial mechanisms responsible for the progression of colorectal cancer in rats.

Chrysophanol Alleviates Metabolic Syndrome by Activating the SIRT6/AMPK Signaling Pathway in Brown Adipocytes.

Chrysophanol, a primary active ingredient of Cassia mimosoides Linn or Rhei radix et rhizoma, has various pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory, as well as blood lipid regulation. However, whether chrysophanol can mitigate obesity, and its underlying mechanisms remains unclear. This study investigated whether chrysophanol effects energy metabolism in high-fat diet- (HFD-) induced obese mice and fat-specific Sirtuin 6- (SIRT6-) knockout (FKO) mice, targeting the SIRT6/AMPK signaling pathway in brown and white fat tissue. Our results showed that chrysophanol can effectively inhibit lipid accumulation in vitro and reduce mice's body weight, improve insulin sensitivity and reduced fat content of mice, and induce energy consumption in HFD-induced obese mice by activating the SIRT6/AMPK pathway. However, a treatment with OSS-128167, an SIRT6 inhibitor, or si-SIRT6, SIRT6 target specific small interfering RNA, in vitro blocked chrysophanol inhibition of lipid accumulation. Similar results were obtained when blocking the AMPK pathway. Moreover, in the HFD-induced obese model with SIRT6 FKO mice, histological analysis and genetic test results showed that chrysophanol treatment did not reduce lipid droplets and upregulated the uncoupling protein 1 (UCP1) expression. Rather, it upregulated the expression of thermogenic genes and activated white fat breakdown by inducing phosphorylation of adenosine 5'-monophosphate- (AMP-) activated protein kinase (AMPK), both in vitro and in vivo. OSS-128167 or si-SIRT6 blocked chrysophanol's upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) and Ucp1 expression. In conclusion, this study demonstrated that chrysophanol can activate brown fat through the SIRT6/AMPK pathway and increase energy consumption, insulin sensitivity, and heat production, thereby alleviating obesity and metabolic disorders.

Prognostic significance of abnormal matrix collagen remodeling in colorectal cancer based on histologic and bioinformatics analysis.

As the major component of the tumor matrix, collagen greatly influences tumor invasion and prognosis. The present study compared the remodeling of collagen and collagenase in 56 patients with colorectal cancer (CRC) using Sirius red stain and immunohistochemistry, exploring the relationship between collagen remodeling and the prognosis of CRC. Weak or strong changes in collagen fiber arrangement in birefringence were observed. With the exception of a higher density, weak changes equated to a similar arrangement in normal collagen, while strong changes facilitated cross­linking into bundles. Compared with normal tissues, collagen I (COL I) and III (COL III) deposition was significantly increased in CRC tissues, and was positively correlated with the metastasis status. In tissues without distant metastasis, collagen IV (COL IV) levels were higher than that in normal tissues, while in tissues with distant metastasis, collagen IV expression was significantly lower. Furthermore, the expression of matrix metalloproteinase (MMP)­1, MMP­2, MMP­7, MMP­9 and lysyl oxidase­like 2 (LOXL2) was found to be elevated in the cancer stroma, which contributed to the hyperactive remodeling of collagen. The association between collagen­related genes and the occurrence and prognosis of CRC were analyzed using biometric databases. The results indicated that patients with upregulated expression of a combination of coding genes for collagen and collagenase exhibited poorer overall survival times. The coding genes COL1A1­2, COL3A1, COL4A3, COL4A6 and MMP2 may therefore be used as biomarkers to predict the prognosis of patients with CRC. Furthermore, the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggest that collagen may promote tumor development by activating platelets. Collectively, the abnormal collagen remodeling, including associated protein and coding genes is associated with the tumorigenesis and metastasis, affecting the prognosis of patients with CRC.

Histone Modifications and their Role in Colorectal Cancer (Review).

The development of colorectal cancer is a complex and multistep process mediated by a variety of factors including the dysregulation of genetic and epigenetic under the influence of microenvironment. It is evident that epigenetics that affects gene activity and expression has been recognized as a critical role in the carcinogenesis. Aside from DNA methylation, miRNA level, and genomic imprinting, histone modification is increasingly recognized as an essential mechanism underlying the occurrence and development of colorectal cancer. Aberrant regulation of histone modification like acetylation, methylation and phosphorylation levels on specific residues is implicated in a wide spectrum of cancers, including colorectal cancer. In addition, as this process is reversible and accompanied by a plethora of deregulated enzymes, inhibiting those histone-modifying enzymes activity and regulating its level has been thought of as a potential path for tumor therapy. This review provides insight into the basic information of histone modification and its application in the colorectal cancer treatment, thereby offering new potential targets for treatment of colorectal cancer.

Geospatial assessment of bioenergy land use and its impacts on soil erosion in the U.S. Midwest.

Agricultural land use change, especially corn expansion since 2000s, has been accelerating to meet the growing bioenergy demand of the United States. This study identifies the environmentally sensitive lands (ESLs) in the U.S. Midwest using the distance-weighted Revised Universal Soil Loss Equation (RUSLE) associated with bioenergy land uses extracted from USDA Cropland Data Layers. The impacts of soil erosion to downstream wetlands and waterbodies in the river basin are counted in the RUSLE with an inverse distance weighting approach. In a GIS-ranking model, the ESLs in 2008 and 2011 (two representative years of corn expansion) are ranked based on their soil erosion severity in crop fields. Under scenarios of bioenergy land use change (corn to grass and grass to corn) on two land types (ESLs and non-ESLs) at three magnitudes (5%, 10% and 15% change), this study assesses the potential environmental impacts of bioenergy land use at a basin level. The ESL distributions and projected trends vary geographically responding to different agricultural conversions. Results support the idea of re-planting native prairie grasses in the identified High and Severe rank ESLs for sustainable bioenergy management in this important agricultural region.

Preoperative CA 15-3 levels predict the prognosis of nonmetastatic luminal A breast cancer.

BACKGROUND: The prognostic value of serum tumor markers (STMs) in nonmetastatic breast cancer patients with different molecular subtypes (luminal A, luminal B, and nonluminal) remains unknown. It is our institutional policy to assess the STMs in nonmetastatic patients. This retrospective single-center study is to investigate the association between STMs and clinical outcomes in nonmetastatic patients and the impact of molecular subtypes. METHODS: A total of 368 patients with available clinical outcomes, tumor node metastasis stages, and STMs levels were included. The serum level of preoperative STMs (carcinoembryonic antigen [CEA], cancer antigen 125 [CA-125], and cancer antigen 15-3 [CA 15-3]) was analyzed and compared among distinct molecular subtypes. Univariate and multivariate analyses were used to investigate the relationship among STMs concentrations and patient outcomes. RESULTS: The median levels of CA 15-3 were 10.2, 8.1 and 7.1 U/mL in patients with luminal A, luminal B, and nonluminal diseases, respectively (P = 0.015). The levels of CEA and CA-125 were similar among the subtypes. Multivariate analysis showed that higher CA 15-3 was significantly associated with worse clinical outcomes exclusively in luminal A patients (P = 0.033 for metastasis-free survival and P = 0.030 for relapse-free survival). In contrast, higher CEA was a significant prognostic factor for worse clinical outcomes (P = 0.003 for metastasis-free survival and P = 0.015 for metastasis-free survival) in nonluminal groups. CONCLUSIONS: The prognostic value of preoperative STMs may be different among molecular subtypes. Patients with luminal A diseases had higher levels of CA 15-3. Higher preoperative CA 15-3 was associated with worse clinical outcomes exclusively in patients with luminal A diseases.

miR-146a and Krüppel-like factor 4 form a feedback loop to participate in vascular smooth muscle cell proliferation.

MicroRNAs are phenotypic regulators of vascular smooth muscle cells (VSMCs). In this paper, we demonstrate that miR-146a targets the Krüppel-like factor 4 (KLF4) 3'-untranslated region and has an important role in promoting VSMC proliferation in vitro and vascular neointimal hyperplasia in vivo. Silencing of miR-146a in VSMCs increases KLF4 expression, whereas overexpression of miR-146a decreases KLF4 levels. Furthermore, we demonstrate that KLF4 competes with Krüppel-like factor 5 (KLF5) to bind to and regulate the miR-146a promoter, and that KLF4 and KLF5 exert opposing effects on the miR-146a promoter. Overexpression of KLF4 in VSMCs decreases miR-146a transcription levels. By using both gain-of-function and loss-of-function approaches, we found that miR-146a promotes VSMC proliferation in vitro. Transfection of antisense miR-146a oligonucleotide into balloon-injured rat carotid arteries markedly decreased neointimal hyperplasia. These findings suggest that miR-146a and KLF4 form a feedback loop to regulate each other's expression and VSMC proliferation.

Krüppel-like factor 4 promotes differentiation by transforming growth factor-beta receptor-mediated Smad and p38 MAPK signaling in vascular smooth muscle cells.

KLF4 (Krüppel-like factor 4) has been implicated in vascular smooth muscle cell (VSMC) differentiation induced by transforming growth factor beta (TGF-beta). However, the role of KLF4 and mechanism of KLF4 actions in regulating TGF-beta signaling in VSMCs remain unclear. In this study, we showed that TGF-beta1 inhibited cell cycle progression and induced differentiation in cultured rat VSMCs. This activity of TGF-beta1 was accompanied by up-regulation of KLF4, with concomitant increase in TbetaRI (TGF-beta type I receptor) expression. KLF4 was found to transduce TGF-beta1 signals via phosphorylation-mediated activation of Smad2, Smad3, and p38 MAPK. The activation of both pathways, in turn, increased the phosphorylation of KLF4, which enabled the formation of KLF4-Smad2 complex in response to TGF-beta1. Chromatin immunoprecipitation studies and oligonucleotide pull-down assays showed the direct binding of KLF4 to the KLF4-binding sites 2 and 3 of the TbetaRI promoter and the recruitment of Smad2 to the Smad-responsive region. Formation of a stable KLF4-Smad2 complex in the promoter's Smad-responsive region mediated cooperative TbetaRI promoter transcription in response to TGF-beta1. These results suggest that KLF4-dependent regulation of Smad and p38 MAPK signaling via TbetaRI requires prior phosphorylation of KLF4 through Smad and p38 MAPK pathways. This study demonstrates a novel mechanism by which TGF-beta1 regulates VSMC differentiation.