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Breast cancer is one of the most prevalent cancers worldwide, and early diagnosis and screening are vital to its successful treatment. Although medical imaging methods can assist in the early detection of breast cancer, imaging methods that are currently used for clinical diagnosis have drawbacks, such as low sensitivity and accuracy. Contrast agents are often used in diagnostic imaging to address these drawbacks. Nanocontrast agents have attracted considerable attention in recent years due to their unique physicochemical characteristics. Among these agents, inorganic nanoprobes have been substantially developed through improvements in synthesis techniques and pairings with other organic molecules. This paper mainly summarizes the specific applications of inorganic nanoprobes in the magnetic resonance imaging, fluorescence imaging, radionuclide imaging, and bimodal/multimodal imaging of breast cancer.

Abstract Background Preoperatively evaluating the feasibility of safe C2 pedicle screw placement is the key to avoiding iatrogenic vertebral artery injury. However, it has not been verified whether the conventional CT measurements of C2 pediculoisthmic component (PIC) are reliable and accurate, and the results may lack validity. The purpose of this study is to analyze the evaluative performance of conventional CT measurements and to create an accurate predictor of morphometrics of C2 PIC. Methods A total of 304 C2 PICs were measured in 152 consecutive patients who underwent CT examination of the cervical spine between April 2020 and December 2020. We obtained the morphometric parameters of C2 PIC by measuring minimum PIC diameter (MPD) in CT multiplanar reconstruction versus conventional measurements of transverse PIC width (TPW), oblique PIC width (OPW) and definition of high-riding vertebral artery (HRVA). The outer diameter measured less than 4 mm in MPD was regarded as the standard of precluding safe C2 pedicle screw insertion. The evaluative performance of the conventional CT measurements was assessed, and the correlation between conventional CT measurements and measurements in CT multiplanar reconstruction was calculated. Results The parameters in OPW and MPD were measured significantly larger than those in TPW, and the preclusion of C2 pedicle screw placement evaluated from TPW and HRVA was significantly higher than that evaluated from OPW and MPD. The sensitivity of TPW was 93.09%, and the specificity was 79.31%. The sensitivity and specificity of OPW were 97.82% and 82.76%. The sensitivity of HRVA was 88.36%, and the specificity was 96.55%. Strong agreement with the highest correlation coefficient (0.879) and determination coefficient (0.7720) suggested that the outer diameter of OPW could be useful for the precise prediction of MPD. Conclusions CT MPR allows accurate measurement of the narrowest section of the C2 PIC. The outer diameter of OPW could be simply measured and be useful for precise prediction of MPD, which makes C2 pedicle screw placement more safely than the conventional measurement of TPW and HRVA.

Identifying the sources of sediments is of great significance in reconstructing Holocene paleoclimate evolution in the Beibu Gulf and in understanding the characteristics of regional responses to changes in global climate. The Holocene paleoclimatic evolutionary history of the Beibu Gulf was investigated by chronological, geochemical, and mineralogical means using the sediments of Core KZK01 from the eastern part of the Beibu Gulf. The rare earth element (REE) distribution curves, (Gd/Yb)N and (La/Yb)N discriminant diagram, and (Gd/Lu)N and ∑LREE/∑HREE discriminant diagram indicated that the detrital materials in the eastern part of the Beibu Gulf primarily originated from Hainan Island and its proximal sources, with considerable contributions from Taiwan and Pearl River materials. Source analysis of clay minerals showed that Luzon Island was the main source of smectite, followed by Hainan Island. Rivers in Taiwan were the main sources of illite in the study area, followed by the Red River. The Red River was the main contributor of chlorite, followed by the Pearl River. Kaolinite mainly originated from Hainan Island and Guangxi. Coastal currents, surface currents, and warm currents were the main drivers of material transport. Paleoclimatic variations since the Holocene in the Beibu Gulf were divided into three stages: 12–9 cal kyr BP, 9–1.3 cal kyr BP, and 1.3 cal kyr BP to the present. During different stages of climatic evolution, drought was often accompanied by cold and humidity coexisted with warmth, and cold-dry-warm-humid alternation is characterized by significant phases. The illite crystallinity clearly recorded the extreme cold events, such as Bond Events (except Bond6) and the Younger Dryas, and the change trend was essentially consistent with the regional climate record, reflecting the control of global climate change on the process of land–sea interaction in the tropical region. Furthermore, it highlights the great potential of illite crystallinity as a proxy indicator for reconstructing the surface chemical weathering processes of the region.

Abstract Background 3-D printing technology has a large spectrum of applications in upper cervical spinal surgery, but none have evaluated the radiological analysis of the feasibility of C2 pedicle screw placement. Thus, this study aimed to perform 3.5-mm-diameter C2 pedicle screw placement on models for performance assessment of CTA-based preoperative screw preclusion. Methods We enrolled 152 patients who underwent CTA of the cervical spine between April 2020 and December 2020. Transverse pediculoisthmic width (TPW), oblique pediculoisthmic width (OPW), minimum pediculoisthmic diameter (MPD), internal height, and isthmus height were measured preoperatively. Subsequently, 1:1 3D-printed bone models were created, and a 3.5-mm-diameter C2 pedicle screw was placed on the models. All 3D-printed models underwent postoperative CT multiplanar reconstruction to evaluate the screw trajectory for the performance assessment of CTA-based preoperative screw preclusion. Results The ROC curves of the MPD, TPW, OPW, Internal height and Isthmus height showed that the optimal cutoff values for each of the five groups were measured values of 4.78, 4.44, 4.37, 4.22 and 5.59 mm, respectively. The AUC, sensitivity, and specificity of MPD were 0.992, 95.1% and 100%, respectively. The MPD had higher metrics than the TPW (AUC, 0.949; sensitivity, 87.9%), internal height (AUC, 0.885; sensitivity, 80.8%; specificity, 84.6%), and isthmus height (AUC, 0.941; sensitivity, 87.2%). We found no evidence of a difference between MPD and OPW in terms of the AUC and sensitivity (0.93 and 95.5%, respectively). Conclusions C2 pedicle screw placement on 3D-printed models is useful for performance assessment of CTA-based preoperative screw preclusion. MPD measurement with CTA multiplanar reconstruction showed the best performance for judging acceptable or unacceptable screws. However, the definition of HRVA could be modified by a 4.2 mm-internal height or by measuring only the isthmus height for judging the preclusion of C2 pedicle screw placement.

Selective internal radiation therapy (SIRT) as one of the radiotherapeutic techniques has been widely used in the treatment of primary and metastatic liver cancer, for better avoiding radiation damage to normal tissues from external exposure. The radioactive microspheres used in SIRT should meet some special requirements closely associated with the type of radionuclides and the size and the property of the microsphere. This review focuses on the radioactive microspheres to elaborate the current challenges in the related fields, including simplification of the preparation of microspheres formed by different materials, visualization of the biodistribution of microspheres, and the suitability of different types of microspheres for repeated treatment. In this context, the major characteristics of three kinds of commercialized radioactive microspheres are compared, the advances in the radioactive microspheres achieved in recent years are summarized, and the future prospects of radioactive microspheres are discussed.

Grassland fires and dust weather in Mongolia can trigger major cascading disasters. Grassland fires from autumn to the following spring can indirectly affect dust weather occurrence in the spring by affecting land surface vegetation cover. In this paper, we selected the aimag (province) of Dornod, Mongolia, a typical temperate grassland area, as the study area. The study aims to (1) analyze the spatiotemporal patterns of grassland fire and dust weather in the past 22 years, as well as the effect of grassland fire on dust weather and to (2) explore in depth the mechanisms of the effects of grassland fire on dust weather. To achieve these goals, we utilize high-resolution satellite burned-area data and Synop dust data. In general, grassland fire and dust weather occurrence clearly varied spatiotemporally across the study area. Grassland fires are typically more frequent in spring and autumn, and dust weather is mainly concentrated in spring. Cumulative grassland fires (both days and burned area) from autumn to the following spring affected the spring cumulative dust weather days significantly, especially the spring cumulative dust storm days. Analysis of the mechanism of the effect of grassland fire on dust storms showed that abundant summer precipitation resulted in higher vegetation cover and more accumulated fuel from autumn to April of the following spring. Consequently, the cumulative grassland fire days were higher, and the cumulative burned area was larger during the period, leading to a significant increase in cumulative dust storm days in May of the spring. In Mongolia, grassland fires are often caused by human factors. The findings of the present study could facilitate the crafting of measures to prevent and reduce grassland fires and indirectly minimize dust weather frequency to protect the ecological environment and promote sustainable development.

Fallopian tube blockage-related diseases are the main cause of female infertility. Diagnosis of tubal patency and accurate determination of tubal obstruction lesions is of great value for infertility treatment. Conventionally, the common used hysterosalpingogram (HSG) has the disadvantages of radioactive hazard and high false positive rate. Thus, the development of a safe and accurate method which can replace traditional HSG for tubal patency diagnosis is urgently needed. Recently, fluorescence imaging in the second near-infrared region (NIR-II) was widely used in in-vivo imaging research due to its excellent tissue penetration and signal-to noise ratio. With the aid of fluorescence agents, NIR-II imaging has the potential to diagnose tubal patency, which, unfortunately, has not been explored. Herein, a kind of rare-earth Erbium-based nanoprobe (Er-RENPs) with outstanding NIR-II fluorescence property was synthesized. Based on the Er-RENPs, the potential of NIR-II fluorescence imaging was explored. Results show that the outline of fallopian tubes can be clearly visualized with the help of Er-RENPs. And the stenotic, occlusive fallopian tubes and hydrosalpinx can be diagnosed. Additionally, the Er-RENPs exhibit good biocompatibility. In this study, we reported that NIR-II rare-earth fluorescent nanoprobe can serve as a promising fluorescent agent, and exhibits considerable potential application for tubal diagnosis.

Abstract Background Fluorescence imaging as the beacon for optical navigation has wildly developed in preclinical studies due to its prominent advantages, including noninvasiveness and superior temporal resolution. However, the traditional optical methods based on ultraviolet (UV, 200–400 nm) and visible light (Vis, 400–650 nm) limited by their low penetration, signal-to-noise ratio, and high background auto-fluorescence interference. Therefore, the development of near-infrared-II (NIR-II 1000–1700 nm) nanoprobe attracted significant attentions toward in vivo imaging. Regrettably, most of the NIR-II fluorescence probes, especially for inorganic NPs, were hardly excreted from the reticuloendothelial system (RES), yielding the anonymous long-term circulatory safety issue. Results Here, we develop a facile strategy for the fabrication of Nd3+-doped rare-earth core–shell nanoparticles (Nd-RENPs), NaGdF4:5%Nd@NaLuF4, with strong emission in the NIR-II window. What’s more, the Nd-RENPs could be quickly eliminated from the hepatobiliary pathway, reducing the potential risk with the long-term retention in the RES. Further, the Nd-RENPs are successfully utilized for NIR-II in vivo imaging and magnetic resonance imaging (MRI) contrast agents, enabling the precise detection of breast cancer. Conclusions The rationally designed Nd-RENPs nanoprobes manifest rapid-clearance property revealing the potential application toward the noninvasive preoperative imaging of tumor lesions and real-time intra-operative supervision. Graphical abstract

Abstract Background As the key regulators in BR signaling, BES1 family genes regulate thousands of target genes involved in various development processes. So far, the functions of BES1 family are poorly understood in tomato, and a comprehensive genomic and expressional analysis is worth to conduct for this family. Results Here, nine SlBES1 family members were identified in tomato and classified into five groups based on the conserved motif, gene structure and phylogenetic analysis. Synteny among tomato, Arabidopsis, pepper and rice were further analyzed to obtain insights into evolutionary characteristics. Several cis-elements related to hormone, stress and plant development were exhibited in the promoter regions of SlBES1 family genes. Subcellular localization showed seven members localized both in the nucleus and cytoplasm, implying the presence of dephosphorylated and phosphorylated form of these seven proteins, furthermore, five of them possessed transcription activation activity whereas the left two functioned as transcriptional repressors. Another two members, however, neither localized in the nucleus nor had transactivation activity. Besides, SlBES1.8 showed flower-specific expression while other members expressed ubiquitously in all organs. Moreover, SlBES1 genes exhibited variational expression in response to nine principal plant hormones. Notably, the expression levels of SlBES1 genes presented a dominant downregulated trend in response to stresses. Conclusions In this study, we systematically analyzed the genomic characterization of SlBES1 family, together with the analyses of protein functional features and expression patterns, our results lay a foundation for the functional research of SlBES1 family.

Chinese herbal polysaccharides (CHPs) are natural polymers composed of monosaccharides, which are widely found in Chinese herbs and work as one of the important active ingredients. Its biological activity is attributed to its complex chemical structure with diverse spatial conformations. However, the structural elucidation is the foundation but a bottleneck problem because the majority of CHPs are heteropolysaccharides with more complex structures. Similarly, the studies on the relationship between structure and function of CHPs are even more scarce. Therefore, this review summarizes the structure-activity relationship of CHPs. Meanwhile, we reviewed the structural elucidation strategies and some new progress especially in the advanced structural analysis methods. The characteristics and applicable scopes of various methods are compared to provide reference for selecting the most efficient method and developing new hyphenated techniques. Additionally, the principle structural modification methods of CHPs and their effects on activity are summarized. The shortcomings, potential breakthroughs, and developing directions of the study of CHPs are discussed. We hope to provide a reference for further research and promote the application of CHPs.

The recent development of silver nanoparticles (AgNPs) has sparked increased interest in biomedical and pharmaceutical applications, leading to the possibility of human exposure. The liver is the primary target organ in the metabolism and transport of nanoparticles. Non-alcoholic fatty liver disease (NAFLD) is the most common and leading cause of hepatic metabolic syndrome with approximately 15% of patients will develop into non-alcoholic steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Thus, the potential hepatotoxicity of AgNPs on NAFLD development and progression should be of great concern. Herein, we explored the potential hepatic effect of a single intravenously injected dose of 0.5, 2.5, and 12.5 mg/kg BW on the liver function of high-fat-diet (HFD)-fed mice for 7 days. AgNP treatment increased serum levels of alanine aminotransferase, aspartate transaminase, triglycerides and cholesterols, the number of lipid droplets, and the contents of triglycerides and cholesterols in NAFLD mice livers compared to HFD-fed mice. The mechanism of AgNP-induced worsen hepatotoxicity in mice is associated with hyperactivation of SREBP-1c-mediated de novo lipogenesis and liver inflammation. Additionally, HFD-fed mice treated with AgNPs had significantly higher oxidative damage and lower global DNA methylation and DNA hydroxymethylation than NAFLD mice. This study suggests that AgNP treatment exacerbated HFD-induced hepatic steatosis, liver inflammation, oxidative stress, and epigenetic changes in mice, which is relevant to the risk of AgNP exposure on NAFLD development and progression.

The barrier membrane plays an extremely critical role in guided bone regeneration (GBR), which determines the success or failure of GBR technology. In order to obtain barrier membranes with high mechanical strength and degradability, some researchers have focused on degradable magnesium alloys. However, the degradation rate of pure Mg-based materials in body fluids is rather fast, thus posing an urgent problem to be solved in oral clinics. In this study, a novel micro-arc oxidation (MAO) surface-treated pure Mg membrane was prepared. Electrochemical tests, immersion experiments and in vivo experiments were carried out to investigate its potential use as a barrier membrane. The experimental results showed that the corrosion resistance of a pure Mg membrane treated by MAO is better than that of the uncoated pure Mg. The results of cell experiments showed no obvious cytotoxicity, which suggests the enhanced differentiation of osteoblasts. At the same time, the MAO-Mg membrane showed better biological activity than the pure Ti membrane in the early stage of implantation, exhibiting relatively good bone regeneration ability. Consequently, the MAO membrane has been proven to possess good application prospects for guided bone regeneration.

Iron oxide nanoparticles (IONPs) as magnetic resonance imaging (MRI) contrast agents have received considerable interest due to their superior magnetic properties. To increase the biocompatibility and blood circulation time, polyethylene glycol (PEG) is usually chosen to decorate IONPs. Although the surface effect induced by the PEGylation has an impact on the relaxometric properties of IONPs and can subsequently affect the imaging results, the occurrence of particle aggregation has troubled researchers to deeply explore this correlation. To shed light on this relationship, three diphosphonate PEGs with molecular weights of 1000, 2000, and 5000 Da were used to replace the hydrophobic oleate ligands of 3.6 nm and 10.9 nm IONPs. Then, the contrast enhancement properties of the resultant “aggregation-free” nanoparticles were carefully evaluated. Moreover, related theories were adopted to predict certain properties of IONPs and to compare with the experimental data, as well as obtain profound knowledge about the impacts of the PEG chain length on transverse relaxivity (r2) and longitudinal relaxivity (r1). It was found that r2 and the saturated magnetization of the IONPs, independent of particle size, was closely related to the chain length of PEG. The results unveiled the correlation between the chain length of the coated PEG and the relaxometric properties of IONPs, providing valuable information which might hold great promise in designing optimized, high-performance IONPs for MRI-related applications.

Semipolar (112¯2) InGaN/GaN superlattice templates with different periodical InGaN layer thicknesses were grown on m-plane sapphire substrates using metal-organic chemical vapor deposition (MOCVD). The strain in the superlattice layers, the relaxation mechanism and the influence of the strain relaxation on the semipolar superlattice template were explored. The results demonstrated that the strain in the (112¯2) InGaN/GaN superlattice templates was anisotropic and increased with increasing InGaN thickness. The strain relaxation in the InGaN/GaN superlattice templates was related to the formation of one-dimension misfit dislocation arrays in the superlattice structure, which caused tilts in the superlattice layer. Whereas, the rate of increase of the strain became slower with increasing InGaN thickness and new misfit dislocations emerged, which damaged the quality of the superlattice relaxed templates. The strain relaxation in the superlattice structure improved the surface microtopography and increased the incorporation of indium in the InGaN epitaxial layers.

Objectives: To use baseline variables to predict one-year disease control for patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) combined with sorafenib as initial treatment by applying a machine learning approach based on the random survival forest (RF) model.Materials and Methods: The multicenter retrospective study included 496 patients with HCC treated with TACE combined with sorafenib between January 2014 and December 2018. The independent risk factors associated with one-year disease control (complete response, partial response, stable disease) were identified using the RF model, and their predictive importance was determined using the Gini index. Tumor response was assessed according to modified Response Evaluation Criteria in Solid Tumors.Results: The median overall survival was 15.5 months. A total of 186 (37.5%) patients achieved positive one-year disease control. The Barcelona Clinic Liver Cancer (BCLC) stage (Gini index: 20.0), tumor size (≤7 cm, >7 cm; Gini index: 9.0), number of lobes involved (unilobar, bilobar; Gini index: 6.4), alpha-fetoprotein level (≤200 ng/dl, >200 ng/dl; Gini index: 6.1), albumin–bilirubin grade (Gini index: 5.7), and number of lesions (1, >1; Gini index: 5.3) were identified as independent risk factors, with the BCLC stage as the most important variable. The RF model achieved a higher concordance index of 0.724 compared to that for the logistic regression model (0.709).Conclusions: The RF model is a simple and accurate approach for prediction of one-year disease control for patients with HCC treated with TACE combined with sorafenib.

It is well known that crop monoculture can induce negative effects on soil ecosystems and crop productivity. However, little is known about how vegetable monoculture affects the soil nematode community structure and its relationship with vegetable yields. In this study, the composition, abundance, metabolic footprint, and ecological indices of soil nematodes are investigated in monocultures of pumpkin and melon. The relationships between nematode community structure and yields of pumpkin and melon were analyzed by linear regression. Both monoculture soils of pumpkin and melon suppressed the relative abundance of bacterivores but increased the relative abundance of plant parasites. Pumpkin monoculture soils decreased soil nematode diversity but increased the maturity index of plant parasites. Monoculture soils of pumpkin and melon decreased the metabolic footprint of lower- and higher-level trophic groups of the soil food web, respectively. Pumpkin and melon monoculture soils increased the food web indices channel index (CI) but decreased the enrichment index (EI) and the structure index (SI). The monoculture soils of pumpkin and melon led to a more fungal-dominated decomposition pathway and degraded soil food web conditions. The abundance of bacterivores and food web indices EI and SI were positively correlated with soil nutrients and pH, while the abundance of plant parasites and CI were negatively correlated with soil nutrients and pH. Paratylenchus was negatively correlated with pumpkin and melon yields and could be the potential plant parasites threatening pumpkin and melon productions. Redundancy analysis showed that monocultures of pumpkin and melon altered the soil nematode community via soil properties; total N, total P, alkeline-N, and pH were the main driving factors.

Cucurbita maxima is one of the most widely cultivated Cucurbitaceae in Heilongjiang province, China. The objectives of this study were to clarify the genetic diversity of 44 accessions from different geographical origins using morphological and molecular characteristics and to compare the consistency of these morphological and molecular characteristics. Morphological characteristics showed a large qualitative variability primarily according to fruit-related traits. Twenty-eight random-amplified polymorphic DNA (RAPD) markers produced 128 bands. Both morphological characteristics and RAPD markers grouped 44 accessions of C. maxima into four clusters, and the similarity coefficients ranged from 0.70 to 0.91 and from 0.40 to 0.98, respectively. DNA polymorphisms were highly consistent with phenotypic traits on rootstock C. maxima. The relationships between C. maxima from different origins were not clearly defined via morphological characteristics and RAPD analysis, suggesting some traits of C. maxima were specific to geographical location had disappeared or were weak in Heilongjiang province, which would not facilitate pumpkin breeding. Hybrid generations and their parent plants or sister lines were grouped into sub-clusters and showed little genetic distance according to both evaluation methods. Overall, morphological characteristics and RAPD markers were consistent and revealed high genetic diversity between C. maxima landraces from different origins.

Attentional control theory indicates that concentration is considered an important variable that contributes to learning. There are some devices for players to practice their concentration, but there are few virtual reality (VR) designs which can increase the level of difficulty for students to discipline their mental concentration with incongruent hands-on movement. To address this gap, a VR system named Tracking Fun was designed, which requires hand-eye coordination to move a ball to a target hole. To explore the effect of playing Tracking-fun on players' concentration performance, the study explored the relationship among entity beliefs of concentration ability (EBCA), intrinsic cognitive load (ICL), failure attribution of VR operation (FAVRO), flow experience, and gameplay performance. Students from a skills-based senior high school took part in this experimental research, and 259 valid questionnaires were returned. The research results showed that: EBCA can positively predict cognitive load; EBCA can positively predict FAVRO; ICL and flow have a negative correlation; FAVRO can negatively predict flow experience when interacting with VR; and flow can negatively predict gameplay performance. Based on the results, enriching the opportunity and difficulty level of Tracking-fun can enhance players' concentration. Follow-up research suggestions are proposed.

Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes mellitus and accounts for about 95% of all diabetes cases. Many newer oral as well as parenteral antidiabetic drugs have been introduced in to the market in recent years to control hyperglycemic conditions in diabetes patients and many of these drugs produce potential side effects in diabetes patients. Hence, this systematic review was aimed to analyze and compare the efficacy and safety of oral antidiabetic agents in controlling HbA1c in T2DM patients, that were approved by the United States-Food and Drug Administration (US-FDA) from 2013 to 2017. All randomized controlled, double-blind trials published in English during the search period involving the newer antidiabetic agents were selected. In the outcome assessment comparison, semaglutide demonstrated the highest efficacy in lowering HbA1c, with a 1.6% reduction (p < 0.0001) when given at a dose of 1.0 mg. The safety profile of all the agents as compared to placebo or control were similar, with no or slight increase in the occurrence of adverse events (AEs) but no fatal reaction was reported. The most common AEs of all the antidiabetic agents were gastrointestinal in nature, with several cases of hypoglycemic events. However, among all these agents, semaglutide seems to be the most efficacious drug to improve glycemic control in terms of HbA1c. Alogliptin has the least overall frequency of AEs compared to other treatment groups.

It is a great challenge to identify optimum technologies for CHP systems that utilise biomass and convert it into heat and power. In this respect, industry decision makers are lacking in confidence to invest in biomass CHP due to economic risk from varying energy demand. This research work presents a linear programming systematic framework to design biomass CHP system based on potential loss of profit due to varying energy demand. Minimax Regret Criterion (MRC) approach was used to assess maximum regret between selections of the given biomass CHP design based on energy demand. Based on this, the model determined an optimal biomass CHP design with minimum regret in economic opportunity. As Feed-in Tariff (FiT) rates affects the revenue of the CHP plant, sensitivity analysis was then performed on FiT rates on the selection of biomass CHP design. Besides, design analysis on the trend of the optimum design selected by model was conducted. To demonstrate the proposed framework in this research, a case study was solved using the proposed approach. The case study focused on designing a biomass CHP system for a palm oil mill (POM) due to large energy potential of oil palm biomass in Malaysia.

Although obesity is one of the strongest risk factors for esophageal adenocarcinoma, the molecular mechanisms underlying this association remain unclear. We recently identified four esophageal adenocarcinoma-specific master regulator transcription factors (MRTF) ELF3, KLF5, GATA6, and EHF. In this study, gene-set enrichment analysis of both esophageal adenocarcinoma patient samples and cell line models unbiasedly underscores fatty acid synthesis as the central pathway downstream of three MRTFs (ELF3, KLF5, GATA6). Further characterizations unexpectedly identified a transcriptional feedback loop between MRTF and fatty acid synthesis, which mutually activated each other through the nuclear receptor, PPARG. MRTFs cooperatively promoted PPARG transcription by directly regulating its promoter and a distal esophageal adenocarcinoma-specific enhancer, leading to PPARG overexpression in esophageal adenocarcinoma. PPARG was also elevated in Barrett's esophagus, a recognized precursor to esophageal adenocarcinoma, implying that PPARG might play a role in the intestinal metaplasia of esophageal squamous epithelium. Upregulation of PPARG increased de novo synthesis of fatty acids, phospholipids, and sphingolipids as revealed by mass spectrometry-based lipidomics. Moreover, ChIP-seq, 4C-seq, and a high-fat diet murine model together characterized a novel, noncanonical, and cancer-specific function of PPARG in esophageal adenocarcinoma. PPARG directly regulated the ELF3 super-enhancer, subsequently activating the transcription of other MRTFs through an interconnected regulatory circuitry. Together, elucidation of this novel transcriptional feedback loop of MRTF/PPARG/fatty acid synthesis advances our understanding of the mechanistic foundation for epigenomic dysregulation and metabolic alterations in esophageal adenocarcinoma. More importantly, this work identifies a potential avenue for prevention and early intervention of esophageal adenocarcinoma by blocking this feedback loop. SIGNIFICANCE: These findings elucidate a transcriptional feedback loop linking epigenomic dysregulation and metabolic alterations in esophageal adenocarcinoma, indicating that blocking this feedback loop could be a potential therapeutic strategy in high-risk individuals.

Abstract Background The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto-oncogenes, such as c-myc, as well as the inactivation of certain tumor suppressors, such as p16. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis. Methods Four groups of rats were given diethylinitrosamine (DEN) and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively), while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of p16 and c-myc mRNA was examined by Real-time PCR (Q-PCR). The DNA methylation status within the p16 and c-myc promoter was analyzed using methylation-specific PCR. Results Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p)-positive foci were decreased in the livers of the rats treated with betaine (P < 0.05). Although the frequency of p16 promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (P > 0.05). Betaine supplementation attenuated the down-regulation of p16 and inhibited the up-regulation of c-myc induced by DEN in a dose-dependent manner (P < 0.01). Meanwhile, increases in levels of malondialdehyde (MDA) and glutathione S-transferase (GST) in model, 2% and 4% betaine groups were observed (P < 0.05). Finally, enhanced antioxidative capacity (T-AOC) was observed in both the 2% and 4% betaine groups. Conclusion Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels.

Abstract Background Despite the use of a series of preventive measures, a high incidence of severe acute respiratory syndrome (SARS) was observed among health care workers (HCWs) during the SARS epidemic. This study aimed to determine which preventive measures may have been effective in protecting HCWs from infection, and which were not effective. Methods A retrospective study was performed among 758 'frontline' health care workers who cared for SARS patients at the Second Affiliated Hospital and the Third Affiliated Hospital of Sun Yat-sen University. The HCWs with IgG against SARS and those without IgG against SARS were respectively defined as the "case group" and the "control group", and logistic regression was conducted to explore the risk factors for SARS infection in HCWs. Results After adjusting for age, gender, marital status, educational level, professional title, and the department in which an individual worked, the results of a multivariate logistic regression analysis indicated that incidence of SARS among HCWs was significantly and positively associated with: performing tracheal intubations for SARS patients, methods used for air ventilation in wards, avoiding face-to-face interaction with SARS patients, the number of pairs of gloves worn by HCWs, and caring for serious SARS cases. Conclusion Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.

ObjectiveWhile oesophageal squamous cell carcinoma remains infrequent in Western populations, the incidence of oesophageal adenocarcinoma (EAC) has increased sixfold to eightfold over the past four decades. We aimed to characterise oesophageal cancer-specific and subtypes-specific gene regulation patterns and their upstream transcription factors (TFs).  DESIGN: To identify regulatory elements, we profiled fresh-frozen oesophageal normal samples, tumours and cell lines with chromatin immunoprecipitation sequencing (ChIP-Seq). Mathematical modelling was performed to establish (super)-enhancers landscapes and interconnected transcriptional circuitry formed by master TFs. Coregulation and cooperation between master TFs were investigated by ChIP-Seq, circularised chromosome conformation capture sequencing and luciferase assay. Biological functions of candidate factors were evaluated both in vitro and in vivo.ResultsWe found widespread and pervasive alterations of the (super)-enhancer reservoir in both subtypes of oesophageal cancer, leading to transcriptional activation of a myriad of novel oncogenes and signalling pathways, some of which may be exploited pharmacologically (eg, leukemia inhibitory factor (LIF) pathway). Focusing on EAC, we bioinformatically reconstructed and functionally validated an interconnected circuitry formed by four master TFs-ELF3, KLF5, GATA6 and EHF-which promoted each other's expression by interacting with each super-enhancer. Downstream, these master TFs occupied almost all EAC super-enhancers and cooperatively orchestrated EAC transcriptome. Each TF within the transcriptional circuitry was highly and specifically expressed in EAC and functionally promoted EAC cell proliferation and survival.ConclusionsBy establishing cancer-specific and subtype-specific features of the EAC epigenome, our findings promise to transform understanding of the transcriptional dysregulation and addiction of EAC, while providing molecular clues to develop novel therapeutic modalities against this malignancy.