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BackgroundProstate cancer is the second most common cancer with a high risk of biochemical recurrence (BCR) among men. Recently, 5-methylcytosine (m5C) modification has attracted more attention as a new layer of RNA post-transcriptional regulation. Hence, we aimed at investigating the potential roles of m5C modification regulators in the BCR of prostate adenocarcinoma (PRAD).MethodsCNV data, mutation annotation data, mRNA expression profiles, and clinical data were downloaded from TCGA and GEO databases. Kaplan-Meier curves analysis, log-rank test, univariate and multivariate Cox regression, and time-dependent ROC curves analysis were performed to evaluate the prognostic factors. Principal components analysis (PCA) was applied to validate the distinction between subgroups. Gene set variation analysis (GSVA) was used to investigate the underlying pathways associated with m5C modification patterns. Single sample gene set enrichment analysis (ssGSEA) was utilized to assess the infiltration of distinct immune cells. Tumor Immune Dysfunction and Exclusion (TIDE) prediction was carried out to assess the potential response to immune checkpoint blockade (ICB) therapy. The m5C modification signature was constructed via LASSO Cox’s proportional hazards regression method.ResultsAfter comprehensively analyzing various types of data from TCGA dataset, and exploring the differential expression and prognostic value of each m5C regulator, we identified m5C modification patterns based on 17 m5C regulators. Two patterns presented a significant difference in the risk of BCR, the tumor microenvironment (TME), and immunotherapy response in PRAD. We found that TET2, which was highly expressed in adjacent normal tissues compared to tumor tissues, was closely associated with many infiltrating immune cells. The m5C modification signature was constructed for the clinical application. Risk score calculated by m5C signature was associated with T stage, N stage, Gleason score, and the possibility of BCR (HR, 4.197; 95% CI, 3.016-5.842; p < 0.001). A higher risk score also represented the possibility of immunotherapy response. Finally, the potential roles of m5C modification signature were validated in the testing dataset.ConclusionsOur study revealed the potential roles of m5C modification in the PRAD BCR and TME diversity, which may provide new insight into the field of prostate cancer in future research.

Severe tracheomalacia (TM) patients with respiratory symptoms need surgical intervention, including aortopexy, internal stents or external splint. While some patients continue to have respiratory symptoms after tracheal relief, and there is no evidence to support any one surgery therapy over another. Here we introduce a clinical safety and efficacy of the three-dimensional (3D)-printed bioresorbable airway external splints in treating congenital heart disease (CHD) patients with severe TM. From May 2019 to September 2020, nine patients with severe TM were enrolled. The median age was 5 months (range, 3–25 months), and the median weight was 7.5 kg (range, 3–15 kg). All patients had wheezing, and two patients were assisted by machine ventilation (MV) preoperatively. The median length of TM was 1.5 cm (range, 1.0–3.0 cm). All patients underwent suspension of a “C”-shaped lumen airway external splint, which were designed in SOLIDWORKS and made of polycaprolactone (PCL). The airway external splint could provided effective support for at least 6 months and was completely degraded into carbon dioxide and water within 2–3 years. The median time of postoperative machine assisted ventilation was 23.7 h (range, 3.3–223.4 h), and the median time of ICU stay was 9 days (range, 4–25 days). The median follow-up time was 18 months (range, 12–24 months). Respiratory symptoms were all relieved, and no external splint-associated complications occurred. The 3D computed tomography reconstruction showed no airway stenosis. Personalized 3D-printed bioresorbable airway external splint can not only limit external compression and prevent airway collapse but also ensure the growth potential of the airway, which is a safe, reliable and effective treatment for CHD with TM.

Glioma is the most common malignant tumor of the central nervous system. Tumor purity is a source of important prognostic factor for glioma patients, showing the key roles of the microenvironment in glioma prognosis. In this study, we systematically screened functional characterization related to the tumor immune microenvironment and constructed a risk model named Glioma MicroEnvironment Functional Signature (GMEFS) based on eight cohorts. The prognostic value of the GMEFS model was also verified in another two glioma cohorts, glioblastoma (GBM) and low-grade glioma (LGG) cohorts, from The Cancer Genome Atlas (TCGA). Nomograms were established in the training and testing cohorts to validate the clinical use of this model. Furthermore, the relationships between the risk score, intrinsic molecular subtypes, tumor purity, and tumor-infiltrating immune cell abundance were also evaluated. Meanwhile, the performance of the GMEFS model in glioma formation and glioma recurrence was systematically analyzed based on 16 glioma cohorts from the Gene Expression Omnibus (GEO) database. Based on multiple-cohort integrated analysis, risk subpathway signatures were identified, and a drug–subpathway association network was further constructed to explore candidate therapy target regions. Three subpathways derived from Focal adhesion (path: 04510) were identified and contained known targets including platelet derived growth factor receptor alpha (PDGFRA), epidermal growth factor receptor (EGFR), and erb-b2 receptor tyrosine kinase 2 (ERBB2). In conclusion, the novel functional signatures identified in this study could serve as a robust prognostic biomarker, and this study provided a framework to identify candidate therapeutic target regions, which further guide glioma patients’ clinical decision.

Natural killer (NK) cells are a type of innate lymphoid cell that are involved in the progression of acute myocardial infarction and ischemic stroke. Although multiple forms of programmed cell death are known to play important roles in these diseases, the correlation between NK cells and apoptosis-related genes during acute myocardial infarction and ischemic stroke remains unclear. In this study, we explored the distinct patterns of NK cell infiltration and apoptosis during the pathological progression of acute myocardial infarction and ischemic stroke using mRNA expression microarrays from the Gene Expression Omnibus database. Since the abundance of NK cells correlated positively with apoptosis in both diseases, we further examined the correlation between NK cell abundance and the expression of apoptosis-related genes. Interestingly, APAF1 and IRAK3 expression correlated negatively with NK cell abundance in both acute myocardial infarction and ischemic stroke, whereas ATM, CAPN1, IL1B, IL1R1, PRKACA, PRKACB, and TNFRSF1A correlated negatively with NK cell abundance in acute myocardial infarction. Together, these findings suggest that these apoptosis-related genes may play important roles in the mechanisms underlying the patterns of NK cell abundance and apoptosis in acute myocardial infarction and ischemic stroke. Our study, therefore, provides novel insights for the further elucidation of the pathogenic mechanism of ischemic injury in both the heart and the brain, as well as potential useful therapeutic targets.

Abstract Background Bud dormancy is a sophisticated strategy which plants evolve to survive in tough environments. Endodormancy is a key obstacle for anti-season culture of tree peony, and sufficient chilling exposure is an effective method to promote dormancy release in perennial plants including tree peony. However, the mechanism of dormancy release is still poorly understood, and there are few systematic studies on the metabolomics during chilling induced dormancy transition. Results The tree peony buds were treated with artificial chilling, and the metabolmics analysis was employed at five time points after 0–4 °C treatment for 0, 7, 14, 21 and 28 d, respectively. A total of 535 metabolites were obtained and devided into 11 groups including flavonoids, amino acid and its derivatives, lipids, organic acids and its derivates, nucleotide and its derivates, alkaloids, hydroxycinnamoyl derivatives, carbohydrates and alcohols, phytohormones, coumarins and vitamins. Totally, 118 differential metabolites (VIP ≥ 1, P

Total 150 sediments samples were collected from the Yangzong Lake, and the total phosphorus, pH, redox potential and organic carbon were analysed to quantitatively study the dispersal and sources of phosphorus and its influential factors. The results indicated that the total phosphorus content in sediments was 318-3931 mg/kg, which decreased slightly with depth. In the sediments at the depths of 0-2cm, 2-4cm, 4-6cm, 6-8cm and 8-10cm, the phosphorus contents were 1151mg/kg, 1126mg/kg, 1138mg/kg, 1057mg/kg and 893mg/kg respectively. The contents of phosphorus in the sediments were high on both north and south banks and reduced gradually towards the centre of the lake. Before the 1980s, the phosphorus distribution in the sediments was mainly influenced by natural factors such as pH value, redox potential and organic matter. But after the 1980s, the phosphorus distribution was mainly affected by the position of sewage discharge. Sources of phosphorus in the sediments have changed from the local source to the multiple sources, and from the point source to surface source. Currently, soil erosion and agricultural non-point source pollution are the main sources of phosphorus in Yangzong Lake.

Abstract Global Navigation Satellite System precise positioning using carrier phase measurements requires reliable ambiguity resolution. It is challenging to obtain continuous precise positions with a high ambiguity fixing rate under a wide range of dynamic scenes with a single base station, thus the positioning accuracy will be degraded seriously. The Forward–Backward Combination (FBC), a common post-processing smoothing method, is simply the weighted average of the positions of forward and backward filtering. When the ambiguity fixing rate of the one-way (forward or backward) filter is low, the FBC method usually cannot provide accurate and reliable positioning results. Consequently, this paper proposed a method to improve the accuracy of positions by integrating forward and backward AR, which combines the forward and backward ambiguities instead of positions—referred to as ambiguity domain-based integration (ADBI). The purpose of ADBI is to find a reliable correct integer ambiguities by making full use of the integer nature of ambiguities and integrating the ambiguities from the forward and backward filters. Once the integer ambiguities are determined correctly and reliably with ADBI, then the positions are updated with the fixing ambiguities constrained, in which more accurate positions with high confidence can be achieved. The effectiveness of the proposed approach is validated with airborne and car-borne dynamic experiments. The experimental results demonstrated that much better accuracy of position and higher ambiguity-fixed success rate can be achieved than the traditional post-processing method.

Abstract Background As a nucleolar protein associated with ribosome biogenesis, pescadillo homolog 1 (PES1) has been reported to participate in the development of many cancers. However, its role in prostate cancer is not clearly defined. Therefore, the aim of this study is to explore the effects and the specific mechanism of PES1 in prostate cancer. Methods A microarray-based analysis was performed to analyze differentially expressed genes (DEGs) between prostate cancer and normal samples. Next, the interaction between PES1 and microRNA-1271 (miR-1271) was investigated using bioinformatics analysis in combination with dual-luciferase reporter gene assay. The expression of miR-1271 in prostate cancer cells and tissues was determined using RT-qPCR. Its effects on downstream estrogen receptor β (ERβ) signaling pathway were further examined. Moreover, we analyzed whether miR-1271 affects proliferation, apoptosis, migration and invasion of prostate cancer cells by EdU assay, flow cytometry, and Transwell assay. Lastly, a prostate cancer mouse model was conducted to measure their roles in the tumor growth. Results PES1 was identified as a prostate cancer-related DEG and found to be upregulated in prostate cancer. miR-1271, which was poorly expressed in both cells and tissues of prostate cancer, can specifically bind to PES1. Additionally, overexpression of miR-1271 activated the ERβ signaling pathway. Overexpression of miR-1271 or depletion of PES1 inhibited prostate cancer cell proliferation, migration and invasion, promoted apoptosis in vitro and suppressed tumor growth in vivo. Conclusions Taken together, overexpression of miR-1271 downregulates PES1 to activate the ERβ signaling pathway, leading to the delayed prostate cancer development. Our data highlights the potential of miR-1271 as a novel biomarker for the treatment of prostate cancer.

Abstract Background Enterocytozoon bieneusi is a parasite that infects humans and a wide range of other animals. The large migratory waterfowl, the whooper swan (Cygnus cygnus), travels through many cities during its migration and can spread parasites. Despite receiving increasing attention worldwide, there have been no reports of E. bieneusi infection occurring in C. cygnus. Therefore, this study aims to assess the prevalence and genetic characteristics of E. bieneusi in C. cygnus in Sanmenxia, China. Methods Altogether, 467 fresh fecal samples were collected in the Swan Wetland Park in Sanmenxia, China. Genomic DNA was extracted from fresh fecal samples (n = 467) and E. bieneusi was identified by nested PCR amplification of the internal transcribed spacer (ITS) region. ITS-positive sequences were aligned and phylogenetically analyzed to determine the genotypes of E. bieneusi. Results The overall prevalence of E. bieneusi in C. cygnus was 7.49% (35/467). Sequencing of the 35 positive samples revealed eight known genotypes (EbpA, EbpC, Henan-III, Henan-IV, BEB6, CD9, Peru6 and PtEb IX) and three novel genotypes (CSW1, CSW2 and CSW3). The phylogenetic tree constructed from the ITS sequences showed that seven genotypes (Peru6, EbpA, EbpC, Henan-III, CSW3, Henan-IV and CSW1) clustered within the zoonotic Group 1 while the remaining novel genotype CSW2 clustered within Group 5. Conclusions To our knowledge, this is the first report of E. bieneusi in C. cygnus. Of public health significance, our results suggest that migratory C. cygnus might play an important role in the water-borne transmission of E. bieneusi. Effective strategies will be necessary to control E. bieneusi infection in C. cygnus, other animals and humans.

This paper reveals the coupling mechanism of government support, financial support, and innovation. Using panel data from 28 provinces in China from 2007 to 2016 as a research sample, the coupling coordination degree model is used to measure the coupling coordination degree of government support, financial support, and innovation, and the empirical analysis of its relationship with economic development is conducted through projection pursuit model, static panel data model and dynamic panel data model. The main results show that: (1) The coupling coordination degree of government support, financial support, and innovation in the eastern, central, and western region is on the rise, but there are large differences between regions. (2) The coupling coordination degree of government support, financial support, and innovation has a significant positive impact on economic development, and there are regional differences in its role in promoting economic development. That is, the coupling coordination degree of government support, financial support, and innovation has significantly promoted the economic development of the eastern region, but has no significant impact on the economic development of the central and western region.

The potential security problems of blockchain technology are constantly restricting the development process of related industrial applications. The cost of deploying a blockchain system in a real environment to conduct research on security issues is relatively high, and the related security analysis and verification are also destructive and irreproducible. Therefore, based on the idea of layered design, this paper proposes a blockchain system simulation platform. The blockchain system is divided into four layers in the simulation platform: the consensus layer, network layer, contract layer, and storage layer. In the consensus layer, the problem of computing resource waste is solved. In the network layer, a peer-to-peer network topology simulation is implemented. In the storage layer, the problem of redundant storage is solved. In the contract layer, the contract replay speed is accelerated. Finally, a prototype of an efficient blockchain simulation system is implemented based on the above methods.

An amendment to this paper has been published and can be accessed via the original article.

Summary: Background: China's three inactivated enterovirus A71 (EV-A71) vaccines are the first and currently world's only EV-A71 vaccines approved by a national regulatory authority and used to prevent EV-A71 associated diseases. The three vaccines vary by vaccine strain, manufacturing cell substrate, and antigen dose, but no head-to-head comparisons of these vaccines have been done. We compared immunogenicity of the vaccines in children 6-35 months old. Methods: We recruited healthy children aged 6-35 months who lived in a study site county into a multicentre, open-label, non-inferiority, three-group, randomised controlled trial that was conducted in five counties in China. Enrolled children were randomly assigned (1:1:1) to receive two doses of one of the three EV-A71 vaccines. The primary outcome was the proportion of children with EV-A71 neutralizing antibody seroconversion 4 weeks after the second dose; a secondary outcome was adverse events in the 4 weeks after each dose. Analyses of immunogenicity included all children who completed the study (per-protocol analysis). Safety analysis included all children completed safety follow-up after at least one. We used a 10% margin to establish non-inferiority. This trial was registered on a World Health Organization platform: Chinese Clinical Trial Registry (ChiCTR1900026663). Findings: 1631 children were assessed for eligibility between Nov 4 and Nov 20, 2019. Of 1500 (92%) enrolled children, 500 were assigned to vaccine group A, B, or C; 483 in group A,484 in group B, and 487 in group C completed the study. Before dose one, the seropositive rates in groups A, B, and C were 9.7%, 7.2%, and 7.0%. Four weeks after the second dose, seroconversion rates of groups A, B, and C were 98.8%, 99.4% and 99.8% - mutually non-inferior in all two-group comparisons. There were no serious adverse events in any group and no evidence of a difference among the three groups in the incidence of local adverse event or systemic adverse event. Fever was the most common adverse event. All children with reported adverse events recovered. Interpretation: Non-inferior and high seroconversion rates and equivalent safety of three EV-A71 vaccines supports use any of these vaccines to prevent EV-A71-associated diseases. These results may be useful for regulators, vaccine policy makers, and immunization programmes in China and in countries where EV-A71 is endemic.

In this paper, the path following of an underactuated ship as a fundamental application for autonomous sailing in seaways is studied. First, the guidance system based on the line of sight (LOS) method is established to handle underactuated dynamics of ship motion. Then, path following control is converted to heading control with fewer dimensions. Second, the extended state observer (ESO) is used to observe unknown dynamics of ship motion. Third, the sliding mode control method is highly robust to external disturbance and is employed to design the controller. Fourth, the event-triggered mechanism (ETM) is included to reduce the trigger time. All the closed-loop signals are shown to be bounded by the Lyapunov theory. Simulations are carried out to verify the effectiveness of the proposed method.

The retina is composed of 11 types of cells, including neurons, glial cells and vascular bed cells. It contains five types of neurons, each with specific physiological, morphological, and molecular definitions. Currently, single-cell RNA sequencing (sRNA-seq) is emerging as one of the most powerful tools to reveal the complexity of the retina. The continuous discovery of retina-related gene targets plays an important role in helping us understand the nature of diseases. The revelation of new cell subpopulations can focus the occurrence and development of diseases on specific biological activities of specific cells. In addition, sRNA-seq performs high-throughput sequencing analysis of epigenetics, transcriptome and genome at the single-cell level, with the advantages of high-throughput and high-resolution. In this paper, we systematically review the development history of sRNA-seq technology, and summarize the new subtypes of retinal cells and some specific gene markers discovered by this technology. The progress in the diagnosis of retinal related diseases is also discussed.

Abstract Background Clear cell sarcoma of the kidney (CCSK) is the second most common renal tumor in children following Wilms’ tumor. CCSK is extremely rare in adults, with only 25 adult cases reported in the medical literature. Case presentation We reported a 62-year-old man with a right renal mass presenting only with generalized pruritus who underwent radical right nephrectomy. With immunostaining, tumor cells were positive for expressed vimentin, neural cell adhesion molecule (NCAM, CD56), and Ki-67 and focally positive for p53, CD10 and Bcl-2. The histopathological diagnosis was CCSK. Two weeks after the operation, the generalized pruritus ended. One month after the operation, the patient started treatment with a regimen combining doxorubicin, vincristine, cyclophosphamide, and etoposide. At the 20-month follow-up visit, there was no evidence of local recurrence or metastases. Conclusions In a patient presenting with generalized pruritus, further evaluation for an underlying malignancy should be considered. It is difficult to distinguish CCSK from undifferentiated renal neoplasms. Immunohistochemistry could help to make exact histopathological diagnoses. The BCL-6 corepressor (BCOR) gene could play a significant role in CCSK tumorigenesis and be a good marker for CCSK diagnosis. Surgery with combination chemotherapy and radiation therapy could be used to treat CCSK in older patients.

Abstract Background Prostate cancer (PCa) is a common disease that often occurs among older men and a frequent cause of malignancy associated death in this group. microRNA (miR)-129-5p has been identified as an essential regulator with a significant role in the prognosis of PC. Therefore, this study aimed to investigate roles of miR-129-5p in PCa. Methods Microarray analysis was conducted to identify PCa-related genes. The expression of miR-129-5p and ZIC2 in PCa tissues was investigated. To understand the role of miR-129-5p and ZIC2 in PCa, DU145 cells were transfected with mimic or inhibitor of miR-129-5p, or si-ZIC2 and the expression of Wnt, β-catenin, E-cadherin, vimentin, N-cadherin, vascular endothelial growth factor (VEGF), and CD31, as well as the extent of β-catenin phosphorylation was determined. In addition, cell proliferation, migration, invasion, angiogenesis, apoptosis and tumorigenesis were detected. Results miR-129-5p was poorly expressed and ZIC2 was highly expressed in PCa tissues. Down-regulation of ZIC2 or overexpression of miR-129-5p reduced the expression of ZIC2, Wnt, β-catenin, N-cadherin, vimentin, and β-catenin phosphorylation but increased the expression of E-cadherin. Importantly, miR-129-5p overexpression significantly reduced cell migration, invasion, angiogenesis and tumorigenesis while increasing cell apoptosis. Conclusions The findings of the present study indicated that overexpression of miR-129-5p or silencing of ZIC2 could inhibit epithelial–mesenchymal transition (EMT) and angiogenesis in PCa through blockage of the Wnt/β-catenin signaling pathway.

A large number of joint friction pairs work during the work of scroll compressors, resulting in high energy consumption and short service life of scroll compressors. To improve the tribological performance of friction pairs of the scroll compressors, the C-MoS2-PTFE (Polytetrafluoroethylene) lubrication coating is prepared through spraying technology on the surface of 4032 aluminum alloy, a common material for scroll compressors. The microstructure of the C-MoS2-PTFE coating was analyzed by X-ray diffractometer (XRD) and scanning electron microscope (SEM), and the wear behavior of the coating under different loads was studied by reciprocating friction and wear testing machine and three-dimensional profiler. The surface of the grinding marks was analyzed by SEM and energy density spectrum (EDS). The performance was compared with the anodized film of 4032 aluminum alloy and the Ni-coated coating of 4032 aluminum alloy. The experimental results show that the C-MoS2-PTFE coating has a dense structure, and the hardness is 35 HV0.1. Under dry friction conditions, the C-MoS2-PTFE coating has excellent wear reduction and wear resistance, and the coefficient of friction and wears rate under different loads are less than those of the anodized film of 4032 aluminum alloy and the Ni-plated coating. The wear mechanisms of C-MoS2-PTFE coating are fatigue wear, adhesive wear, abrasive wear, and oxidation wear under different loads.

Objectives: This study aimed to evaluate the level and factors affecting the perioperative exercise intention in China.Design: This study was a cross-sectional survey in Southwest China.Methods: Four hundred and ninety nine participants were randomly sampled in eight medical centers from November 23, 2020 to November 27, 2020. The survey included sociodemographic information and a 24-item modified questionnaire, which aimed to evaluate the attitude toward daily exercise, perception of perioperative exercise, social support and the perioperative exercise intention. A multivariable linear regression model was used to evaluate the effect of different items on the patients' intention for perioperative exercise.Results: A total of 523 responses (95.09%) were collected and 499 (95.41%) were analyzed. The level of exercise intention of the patients during the perioperative period was: 14.83% planned to exercise every day in the hospital, 21.04% planned to exercise every other day, and 35.87% planned to exercise every week. Intensity of daily exercise (P = 0.016), positive attitude of daily exercise (P < 0.001), positive attitude of perioperative exercise (P < 0.001) and social support (P < 0.001) were positively associated with the intention for perioperative exercise. Female (P = 0.012), non-tertiary center (P = 0.011), and preoperative anxiety (P = 0.023) was negatively associated with it.Conclusions: The intention for perioperative exercise was low in Southwest China. The authors aimed to relieve preoperative anxiety, promote the education of perioperative exercise, design perioperative exercise programs, and provide more social support from medical staff and family for inpatients undergoing elective surgery.

The dynamics of Leaf Area Index (LAI) from space is key to identify crop types and their phenology over large areas, and to characterize spatial variations within growers’ fields. However, for years remote-sensing applications have been constrained by a trade-off between the spatial and temporal resolutions. This study resolves this limitation. Over the past decade, the number of companies and organizations developing CubeSat constellations has increased. These new satellites make it possible to acquire large image collections at high spatial and temporal resolutions at a relatively low cost. However, the images obtained from CubeSat constellations frequently suffer from inconsistency in the data calibration between the different satellites within the constellation. To overcome these inconsistencies, a new method to fuse a time series of images sourced from two different satellite constellations is proposed, combining the advantages of both (i.e., the temporal, spatial and spectral resolution). This new technique was applied to fuse PlanetScope images with Sentinel-2 images, to create spectrally-consistent daily images of wheat LAI at a 3 m resolution. The daily 3 m LAI estimations were compared with 57 in-situ wheat LAI measurements taken in Australia and Israel. This approach was demonstrated to successfully estimate Green LAI (LAI before the major on-set of leaf senescence) with an R2 of 0.94 and 86% relative accuracy (RMSE of 1.37) throughout the growing season without using any ground calibration. However, both the Sentinel-2 based estimates and the fused Green LAI were underestimated at high LAI values (LAI > 3). To account for this, regression models were developed, improving the relative accuracy of the Green LAI estimations by up to a further 47% (RMSE of 0.35–0.63) in comparison with field measured LAI. The new time series fusion method is an effective tool for continuous daily monitoring of crops at high-resolution over large scales, which opens up a range of new precision agriculture applications. These high spatio-temporal resolution time-series are valuable for monitoring crop growth and health, and can improve the effectiveness of farming practices and enhance yield forecasts at the field and sub-field scales.

Ovarian cancer is the most frequent cause of death among gynecologic malignancies. A total of 80% of patients who have completed platinum-based chemotherapy suffer from relapse and develop resistance within 2 years. In the present study, we obtained patients' complete platinum (cisplatin and carboplatin) medication information from The Cancer Genome Atlas database and then divided them into two categories: resistance and sensitivity. Difference analysis was performed to screen differentially expressed genes (DEgenes) related to platinum response. Subsequently, we annotated DEgenes into the protein–protein interaction network as seed nodes and analyzed them by random walk. Finally, second-ranking protease serine 1 gene (PRSS1) was selected as a candidate gene for verification analysis. PRSS1's expression pattern was continuously studied in Oncomine and cBio Cancer Genomic Portal databases, revealing the key roles of PRSS1 in ovarian cancer formation. Hereafter, we conducted in-depth explorations on PRSS1's platinum response to ovarian cancer through tissue and cytological experiments. Quantitative real-time polymerase chain reaction and Western blot assay results indicated that PRSS1 expression levels in platinum-resistant samples (tissue/cell) were significantly higher than in samples sensitive to platinum. By cell transfection assay, we observed that knockdown of PRSS1 reduced the resistance of ovarian cancer cells to cisplatin. Meanwhile, overexpression of PRSS1 increased the resistance to cisplatin. In conclusion, we identified a novel risk gene PRSS1 related to ovarian cancer platinum response and confirmed its key roles using multiple levels of low-throughput experiments, revealing a new treatment strategy based on a novel target factor for overcoming cisplatin resistance in ovarian cancer.

We provide an assessment of the impact of government closure and containment measures on deaths from COVID-19 across sequential waves of the COVID-19 pandemic globally. Daily data was collected on a range of containment and closure policies for 186 countries from January 1, 2020 until March 11th, 2021. These data were combined into an aggregate stringency index (SI) score for each country on each day (range: 0-100). Countries were divided into successive waves via a mathematical algorithm to identify peaks and troughs of disease. Within our period of analysis, 63 countries experienced at least one wave, 40 countries experienced two waves, and 10 countries saw three waves, as defined by our approach. Within each wave, regression was used to assess the relationship between the strength of government stringency and subsequent deaths related to COVID-19 with a number of controls for time and country-specific demographic, health system, and economic characteristics. Across the full period of our analysis and 113 countries, an increase of 10 points on the SI was linked to 6 percentage points (P < 0.001, 95% CI = [5%, 7%]) lower average daily deaths. In the first wave, in countries that ultimately experiences 3 waves of the pandemic to date, ten additional points on the SI resulted in lower average daily deaths by 21 percentage points (P < .001, 95% CI = [8%, 16%]). This effect was sustained in the third wave with reductions in deaths of 28 percentage points (P < .001, 95% CI = [13%, 21%]). Moreover, interaction effects show that government policies were effective in reducing deaths in all waves in all groups of countries. These findings highlight the enduring importance of non-pharmaceutical responses to COVID-19 over time.

Object detection in remote sensing images (RSIs) requires the locating and classifying of objects of interest, which is a hot topic in RSI analysis research. With the development of deep learning (DL) technology, which has accelerated in recent years, numerous intelligent and efficient detection algorithms have been proposed. Meanwhile, the performance of remote sensing imaging hardware has also evolved significantly. The detection technology used with high-resolution RSIs has been pushed to unprecedented heights, making important contributions in practical applications such as urban detection, building planning, and disaster prediction. However, although some scholars have authored reviews on DL-based object detection systems, the leading DL-based object detection improvement strategies have never been summarized in detail. In this paper, we first briefly review the recent history of remote sensing object detection (RSOD) techniques, including traditional methods as well as DL-based methods. Then, we systematically summarize the procedures used in DL-based detection algorithms. Most importantly, starting from the problems of complex object features, complex background information, tedious sample annotation that will be faced by high-resolution RSI object detection, we introduce a taxonomy based on various detection methods, which focuses on summarizing and classifying the existing attention mechanisms, multi-scale feature fusion, super-resolution and other major improvement strategies. We also introduce recognized open-source remote sensing detection benchmarks and evaluation metrics. Finally, based on the current state of the technology, we conclude by discussing the challenges and potential trends in the field of RSOD in order to provide a reference for researchers who have just entered the field.

In order to investigate the characteristics of the condensate absorption capacity in an exposed sandy bottom when water recedes, the characteristics of condensate variation, condensate formation time, condensate volume, and its absorption capacity were investigated in July 2021, using a micro-osmometer. The research area was the artificial water-retention layer and bare ground of the exposed sandy bottom, formed under the influence of the warming-wetting trend that occurs when water recedes in the salt-lake area of the Qinghai-Tibet Plateau, as well as two conditions: underpass and under sealed. According to the results, the time of condensation generation during the observation period in the salt-lake area of Hoh Xil begins at about 0:00 and ends at about 10:00 The artificial water-retention layer had little influence on the condensation generation time, and the trend of the condensation rate is the same. The unidirectional condensation of water in near-surface air is significantly better under artificial water-retention layer conditions than under bare ground conditions, with condensation occurring three times more frequently than under bare ground conditions. The amount of water condensation in the lower part of the soil under artificial aquifer conditions is 2.588 times greater than that in the near-ground air, while the amount of water condensation in the lower part of the soil under bare ground conditions is 1.783 times greater than that in the near-ground air. The total amount of bi-directional condensation under artificial water-retention layer conditions is slightly less than that in bare ground conditions, while the total amount of unidirectional condensation under artificial water-retention layer conditions is significantly higher, indicating that the artificial water-retention layer contributes to the absorption of water from near-surface air. Due to the presence of permafrost in the Qinghai-Tibet Plateau region, the zero-flux surface transport of evanescent heat in the salt-lake area of Hoh Xil lies approximately within 30 cm from the surface to the ground. The analogous humidity coefficient characterizes the condensate absorption capacity coefficient as the storage capacity of condensate in the surface layer of the soil in a certain area, providing strong evidence that the condensate absorption capacity is higher under the artificial water-retention layer conditions than in bare ground, regardless of whether the condensation is bi-directional or unidirectional. The results of this study can provide a theoretical basis for condensate absorption capacity and vegetation restoration in the bare ecologically degraded areas of the lake bottom.

Background The purpose of this meta‐analysis is to assess the effects of exercise training on quality of life, specific biomarkers, exercise capacity, and vascular function in congenital heart disease (CHD) subjects after surgery. Methods and Results We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE from the date of the inception of the database through April 2019. Altogether, 1161 records were identified in the literature search. Studies evaluating outcomes before and after exercise training among postoperative patients with congenital heart disease were included. The assessed outcomes were exercise capacity, vascular function, serum NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels and quality of life. We analyzed heterogeneity by using the I2 statistic and evaluated the evidence quality according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. Nine randomized controlled trials were included. The evidence indicated that exercise interventions increased the one of the quality of life questionnaire score (mean difference=3.19 [95% CI, 0.23, 6.16]; P=0.03; I2=39%) from the score before the interventions. However, no alterations in exercise capacity, vascular function, NT‐proBNP or quality of life were observed after exercise training. The results of the subgroup analysis showed that NT‐proBNP levels were lower in the group with exercise training than in the group without exercise training over the same duration of follow‐up. The evidence quality was generally assessed to be low. Conclusions In conclusion, there is insufficient evidence to suggest that physical exercise improves long‐term follow‐up outcomes of congenital heart disease, although it has some minor effects on quality of life.

We proposed an optical fiber curvature sensor based on two microcollapses in silica capillary that was spliced between single-mode fibers. Only commercial fiber fusion splicer was needed in the fabrication process. The two microcollapses in the silica capillary can improve the interference effect of light modes with ring distribution surrounding the ultrafine air core (internal diameter of 5 μm), and the axisymmetric mode distribution is easy to be affected by the curving of the capillary. The proposed fiber structure can be used as a cost-effective curvature sensor owing to its simple fabrication process, low fabrication cost, good repeatability, ultrahigh sensitivity (885.62 nm/m-1), and low temperature crosstalk (29 pm/°C).

Heavy metal removal from polluted water is of global significance, but current adsorbents are limited by their specificity towards certain metals. Here the authors incorporate a non-specific and strong chelating group into a robust metal-organic framework and demonstrate its versatility for heavy metal adsorption.

Optimised farm crop productivity requires careful management in response to the spatial and temporal variability of yield. Accordingly, combination of crop simulation models and remote sensing data provides a pathway for providing the spatially variable information needed on current crop status and the expected yield. An ensemble Kalman filter (EnKF) data assimilation framework was developed to assimilate plant and soil observations into a prediction model to improve crop development and yield forecasting. Specifically, this study explored the performance of assimilating state observations into the APSIM-Wheat model using a dataset collected during the 2018/19 wheat season at a farm near Cora Lynn in Victoria, Australia. The assimilated state variables include (1) ground-based measurements of Leaf Area Index (LAI), soil moisture throughout the profile, biomass, and soil nitrate-nitrogen; and (2) remotely sensed observations of LAI and surface soil moisture. In a baseline scenario, an unconstrained (open-loop) simulation greatly underestimated the wheat grain with a relative difference (RD) of −38.3%, while the assimilation constrained simulations using ground-based LAI, ground-based biomass, and remotely sensed LAI were all found to improve the RD, reducing it to −32.7%, −9.4%, and −7.6%, respectively. Further improvements in yield estimation were found when: (1) wheat states were assimilated in phenological stages 4 and 5 (end of juvenile to flowering), (2) plot-specific remotely sensed LAI was used instead of the field average, and (3) wheat phenology was constrained by ground observations. Even when using parameters that were not accurately calibrated or measured, the assimilation of LAI and biomass still provided improved yield estimation over that from an open-loop simulation.

Polymeric adsorbents with different properties were synthesized via suspension polymerization. Equilibrium and kinetics experiments were then performed to verify the adsorption capacities of the resins for molecules of various sizes. The adsorption of small molecules reached equilibrium more quickly than the adsorption of large molecules. Furthermore, the resins with small pores are easy to lower their adsorption capacities for large molecules because of the pore blockage effect. After amination, the specific surface areas of the resins decreased. The average pore diameter decreased when the resin was modified with either primary or tertiary amines, but the pore diameter increased when the resin was modified with secondary amines. The phenol adsorption capacities of the amine-modified resins were reduced because of the decreased specific area. The amine-modified resins could more efficiently adsorb reactive brilliant blue 4 owing to the presence of polar functional groups.

Abstract The luxS gene is required for autoinducer-2 (AI-2) synthesis in many bacterial species. AI-2 is taken up by a specific receptor to regulate multiple bacterial activities. However, the lack of methods to identify AI-2 receptors has impeded investigations into the roles of AI-2. Here, a luxS mutant of Escherichia coli strain BL21 (DE3) was constructed (named BL21∆luxS), and the recombinant LsrB protein of Salmonella enterica was expressed in BL21∆luxS and BL21 cells, which were named LsrB (BL21∆luxS) and LsrB (BL21), respectively. The results of the activity of recombinant LsrB binding showed that LsrB (BL21) bound to endogenous AI-2 (produced from BL21 strain), while LsrB (BL21∆luxS) did not (as BL21∆luxS cannot produce AI-2). However, the results of recombinant LsrB binding showed that LsrB (BL21∆luxS) can bind exogenous AI-2, which was released from LsrB (BL21∆luxS) at 55 °C for 10 min, while LsrB (BL21) could not bind exogenous AI-2 (due to binding of endogenous AI-2 before). Furthermore, analysis of the thermal stability of AI-2 showed that that AI-2 activity was relatively high at incubation temperatures below 65 °C. These findings will be beneficial for screening of new AI-2 receptors in different bacterial species.

Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

Here, two-dimensional FFT and two-dimensional CA-CFAR are combined to process echoes of LFMCW radar based on ZYNQ, which are implemented on hardware, using parallel feature of ZYNQ to improve processing speed. With the high accurate information of two-dimensional FFT and two-dimensional CA-CFAR, the velocity and range information of echo signal is extracted. The coupling problem of velocity and range is solved and the situation of alarm leakage in multi-target is avoided. First, the basic form of the LFMCW signal is introduced. Then, the implementation flow of 2D-FFT and 2D CA-CFAR is described in detail. At last, the conclusion is given by analysing the results of the tested data processed by ZYNQ and is compared with 1D-FFT combined with 1D-CFAR.

Aiming at the problem of radar sensor registration on a mobile platform, this study uses multiple radars to estimate the biases of the radar under the earth-centred earth-fixed coordinate system, which provides more accurate information for data fusion. Compared to the maximum likelihood registration (MLR) algorithm, which can only estimate radar offset biases, a novel extended MLR (EMLR) algorithm is proposed. The algorithm could estimate radar-offset biases, attitude biases, and the target real location simultaneously. The simulation results verified that the EMLR algorithm can effectively improve the precision of registration.

The development of radar signal simulator in specific environment can effectively accelerate the debugging process of radar system and reduce the consumption of human, material, and financial resources. This study analyses the mathematical model of the IF radar signal in aerial distributed semi-active radar system and deduces the parameters of radar signals based on direct digital synthesiser (DDS) technology. After solving the problem of multi-channel synchronisation, delay precision control, and envelope delay compensation, an IF radar signal simulator system was designed and implemented, which can generate three direct-path-wave signals and three echo signals.

This study addresses the target localisation problem using bistatic range (BR) measurements in a multi-base system based on external emitter radar. An asymptotically efficient Taylor series method is proposed for target localisation. The initial value for Taylor series method is provided by some algebraic closed-form positioning algorithms, rather than priori initial guesses. The localisation convergence problem can also be avoided unless in an extremely large measurement noise. The proposed method can be applied to both critically determined and over-determined conditions. The performance is verified and evaluated through simulations. The results show that the method can realise Cramer-Rao lower bound (CRLB) precision under Gaussian measurement noise. In addition, the method is superior to the existing localisation estimation in positioning accuracy and robustness.

The expansion of lipid droplets (LDs) and the differentiation of preadipocytes are two important aspects of mammalian lipid storage. In this study, we examined the role of CDP-diacylglycerol (DAG) synthases (CDSs), encoded by CDS1 and CDS2 genes in mammals, in lipid storage. CDS enzymes catalyze the formation of CDP-DAG from phosphatidic acid (PA). Knocking down either CDS1 or CDS2 resulted in the formation of giant or supersized LDs in cultured cells. Moreover, depleting CDS1 almost completely blocked the differentiation of 3T3-L1 preadipocytes, whereas depleting CDS2 had a moderate inhibitory effect on adipocyte differentiation. The levels of many PA species were significantly increased upon knocking down CDS1. In contrast, only a small number of PA species were increased upon depleting CDS2. Importantly, the amount of PA in the endoplasmic reticulum was dramatically increased upon knocking down CDS1 or CDS2. Our results suggest that the changes in PA level and localization may underlie the formation of giant LDs as well as the block in adipogenesis in CDS-deficient cells. We have therefore identified CDS1 and CDS2 as important novel regulators of lipid storage, and these results highlight the crucial role of phospholipids in mammalian lipid storage.

Females and males are known to have different abilities to cope with stress and disease. This study was designed to investigate the effect of sex on properties of a complex interlinked network constructed of central biochemical metabolites. The study involved the blood collection and analysis of a large set of blood metabolic markers from a total of 236 healthy participants, which included 140 females and 96 males. Metabolic profiling yielded concentrations of 168 metabolites for each subject. A differential correlation network analysis approach was developed for this study that allowed detection and characterization of interconnection differences in metabolites in males and females. Through topological analysis of the differential network that depicted metabolite differences in the sexes, we identified metabolites with high centralities in this network. These key metabolites were identified as 10 phosphatidylcholines (PCaaC34:4, PCaaC36:6, PCaaC34:3, PCaaC42:2, PCaeC38:1, PCaeC38:2, PCaaC40:1, PCaeC34:1, PC aa C32:1 and PC aa C40:6) and 4 acylcarnitines (C3-OH, C7-DC, C3 and C0). Identification of these metabolites may help further studies of sex-specific differences in the metabolome that may underlie different responses to stress and disease in males and females.

Certain microbes in the intestine secrete protein that stimulates the proliferation of beta cells in the pancreas during development.

Regenerative capacity varies greatly between species. Mammals are limited in their ability to regenerate damaged cells, tissues and organs compared to organisms with robust regenerative responses, such as zebrafish. The regeneration of zebrafish tissues including the heart, spinal cord and retina requires foxp3a+ zebrafish regulatory T cells (zTregs). However, it remains unclear whether the muted regenerative responses in mammals are due to impaired recruitment and/or function of homologous mammalian regulatory T cell (Treg) populations. Here, we explore the possibility of enhancing zTreg recruitment with pharmacological interventions using the well-characterized zebrafish tail amputation model to establish a high-throughput screening platform. Injury-infiltrating zTregs were transgenically labelled to enable rapid quantification in live animals. We screened the NIH Clinical Collection (727 small molecules) for modulators of zTreg recruitment to the regenerating tissue at three days post-injury. We discovered that the dopamine agonist pramipexole, a drug currently approved for treating Parkinson’s Disease, specifically enhanced zTreg recruitment after injury. The dopamine antagonist SCH-23390 blocked pramipexole activity, suggesting that peripheral dopaminergic signaling may regulate zTreg recruitment. Similar pharmacological approaches for enhancing mammalian Treg recruitment may be an important step in developing novel strategies for tissue regeneration in humans.

Cellulophaga algicola DSM 14237, isolated from the Eastern Antarctic coastal zone, was found to be able to hydrolyze several types of polysaccharide materials. In this study, a predicted β-agarase (CaAga1) from C. algicola was heterologously expressed in Escherichia coli. The purified recombinant CaAga1 showed specific activities of 29.39, 20.20, 14.12, and 8.99 U/mg toward agarose, pure agar, and crude agars from Gracilaria lemaneiformis and Porphyra haitanensis, respectively. CaAga1 exhibited an optimal temperature and pH of 40 °C and 7, respectively. CaAga1 was stable over a wide pH range from 4 to 11. The recombinant enzyme showed an unusual thermostability, that is, it was stable at temperature below or equal to 40 °C and around 70 °C, but was thermolabile at about 50 °C. With the agarose as the substrate, the Km and Vmax values for CaAga1 were 1.19 mg/mL and 36.21 U/mg, respectively. The reducing reagent (dithiothreitol) enhanced the activity of CaAga1 by more than one fold. In addition, CaAga1 was salt-tolerant given that it retained approximately 70% of the maximum activity in the presence of 2 M NaCl. The thin layer chromatography results indicated that CaAga1 is an endo-type β-agarase and efficiently hydrolyzed agarose into neoagarotetraose (NA4) and neoagarohexaose (NA6). A structural model of CaAga1 in complex with neoagarooctaose (NA8) was built by homology modeling and explained the hydrolysis pattern of CaAga1.

The MPT transports Pi to synthesize ATP. PsMPT, a chilling-induced gene, was previously reported to promote energy metabolism during bud dormancy release in tree peony. In this study, the regulatory elements of PsMPT promoter involved in chilling response were further analyzed. The PsMPT transcript was detected in different tree peony tissues and was highly expressed in the flower organs, including petal, stigma and stamen. An 1174 bp of the PsMPT promoter was isolated by TAIL-PCR, and the PsMPT promoter::GUS transgenic Arabidopsis was generated and analyzed. GUS staining and qPCR showed that the promoter was active in mainly the flower stigma and stamen. Moreover, it was found that the promoter activity was enhanced by chilling, NaCl, GA, ACC and NAA, but inhibited by ABA, mannitol and PEG. In transgenic plants harboring 421 bp of the PsMPT promoter, the GUS gene expression and the activity were significantly increased by chilling treatment. When the fragment from -421 to -408 containing a MYC cis-element was deleted, the chilling response could not be observed. Further mutation analysis confirmed that the MYC element was one of the key motifs responding to chilling in the PsMPT promoter. The present study provides useful information for further investigation of the regulatory mechanism of PsMPT during the endo-dormancy release.

Location-based information has recently been exploited to assist the aggregated process of data, thereby reducing the spatial redundancy efficiently. The constraints nature in 6LoWPAN becomes one of the major concerns in data aggregation methods. However, traditional CSMA/CA in MAC layer may cause significant transmission and control overhead as well as delay on listening and competing for channels. It is a low efficient way to transfer IPv6 packet due to the big packet header. To overcome these shortages, in this paper, we propose LDAA, a location-based novel data aggregation model that aggregates data from the network layer according to the MAC layer queuing delay. When the queuing delay becomes larger, more packets will be dynamically aggregated into one packet to increase the proportion of application data. Otherwise, the amount of packets involved in aggregation will decrease to improve channels utilization. Simulation results show that our approach could provide better real-time guarantees and reduce data spatial redundancy and energy consumption efficiently.

Testosterone deficiency is associated with sickle cell disease (SCD), but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle) exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH) levels compared with wild type (WT) mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol)- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR), but not cholesterol side-chain cleavage enzyme (P450scc), in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi) exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease.

Malate dehydrogenase (MDH) plays important metabolic roles in bacteria. In this study, the recombinant MDH protein (His-MDH) of Brucella abortus was purified and its ability to catalyze the conversion of oxaloacetate (OAA) to L-malate (hereon referred to as MDH activity) was analyzed. Michaelis Constant (Km) and Maximum Reaction Velocity (Vmax) of the reaction were determined to be 6.45×10−3 M and 0.87 mM L−1 min−1, respectively. In vitro studies showed that His-MDH exhibited maximal MDH activity in pH 6.0 reaction buffer at 40°C. The enzymatic activity was 100%, 60%, and 40% inhibited by Cu2+, Zn2+, and Pb2+, respectively. In addition, six amino acids in the MDH were mutated to investigate their roles in the enzymatic activity. The results showed that the substitutions of amino acids Arg 89, Asp 149, Arg 152, His 176, or Thr 231 almost abolished the activity of His-MDH. The present study will help to understand MDH’s roles in B. abortus metabolism.

Endo-dormant flower buds must pass through a period of chilling to reinitiate growth and subsequent flowering, which is a major obstacle to the forcing culture of tree peony in winter. Customized cDNA microarray (8×15 K element) was used to investigate gene expression profiling in tree peony 'Feng Dan Bai' buds during 24 d chilling treatment at 0-4°C. According to the morphological changes after the whole plants were transferred to green house, endo-dormancy was released after 18 d chilling treatment, and prolonged chilling treatment increased bud break rate. Pearson correlation hierarchical clustering of sample groups was highly consistent with the dormancy transitions revealed by morphological changes. Totally 3,174 significantly differentially-expressed genes (P

Lipid droplets (LDs) are important cellular organelles that govern the storage and turnover of lipids. Little is known about how the size of LDs is controlled, although LDs of diverse sizes have been observed in different tissues and under different (patho)physiological conditions. Recent studies have indicated that the size of LDs may influence adipogenesis, the rate of lipolysis and the oxidation of fatty acids. Here, a genome-wide screen identifies ten yeast mutants producing "supersized" LDs that are up to 50 times the volume of those in wild-type cells. The mutated genes include: FLD1, which encodes a homologue of mammalian seipin; five genes (CDS1, INO2, INO4, CHO2, and OPI3) that are known to regulate phospholipid metabolism; two genes (CKB1 and CKB2) encoding subunits of the casein kinase 2; and two genes (MRPS35 and RTC2) of unknown function. Biochemical and genetic analyses reveal that a common feature of these mutants is an increase in the level of cellular phosphatidic acid (PA). Results from in vivo and in vitro analyses indicate that PA may facilitate the coalescence of contacting LDs, resulting in the formation of "supersized" LDs. In summary, our results provide important insights into how the size of LDs is determined and identify novel gene products that regulate phospholipid metabolism.