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Many hypotrich genera, including Trachelostyla, are taxonomically challenging and in a need of integrative revision. Using morphological data, molecular phylogenetic analyses, and internal transcribed spacer 2 (ITS2) secondary structures, we attempt to cast more light on species relationships within the genus Trachelostyla. The present multifaceted approach reveals that (1) a large-sized species with numerous macronuclear nodules, isolated from sandy littoral sediments in southern China, is new to science and is endowed here with a name, T. multinucleata spec. nov.; (2) two other Chinese populations previously identified as T. pediculiformis represent undescribed species; and (3) multigene phylogeny is more robust than single-gene trees, recovering the monophyly of the genus Trachelostyla with high bootstrap frequency. Additionally, ITS2 secondary structures and the presence of compensatory base changes in helices A and B indicate the presence of four distinct taxa within the molecularly studied members of the genus Trachelostyla. Molecular data are more suitable for delimitation of Trachelostyla species than morphological characters as interspecific pairwise genetic distances of small subunit (18S) rDNA, ITS1-5.8S-ITS2, and large subunit (28S) rDNA sequences do not overlap, whereas ranges of multiple morphometric features might transcend species boundaries.

Human cancers are often complicated with increased incidences of blood vessel occlusion, which are mostly insensitive to anticoagulation therapy. We searched for causal factors of cancer-associated embolism. A total of 2,017 blood samples was examined for visible abnormalities. Examined were peripheral blood samples from cancer patients who were about to undergo surgical treatment for genitourinary, breast, gastrointestinal or abdominal tumors. Samples from ambulatory patients being treated for recurrent or castration-resistant prostate cancers were included in the study. The lipid-rich nature was studied with lipophilic stains and lipid panel analysis, while surface membrane was assessed with specific staining and antibody detection. We identified a new entity, lipid droplet-like objects or circulating fatty objects (CFOs), visible in the blood samples of many cancer patients, with the potential of causing embolism. CFOs were defined as lipid-rich objects with a membrane, capable of gaining in volume through interaction with peripheral blood mononuclear cells in ex vivo culture. Blood samples from pancreatic cancer patients were found to have the highest CFO incidence and largest CFO numbers. Most noticeably, CFOs from many pancreatic cancer samples presented as large clusters entangled in insoluble fiber networks, suggestive of intravascular clotting. This study identifies CFO as an abnormal entity in cancer patient blood, and a contributory factor to intravascular embolism during cancer development and progression.

Background. Type 2 diabetes (T2D) as a worldwide chronic disease combined with the COVID-19 pandemic prompts the need for improving the management of hospitalized COVID-19 patients with preexisting T2D to reduce complications and the risk of death. This study aimed to identify clinical factors associated with COVID-19 outcomes specifically targeted at T2D patients and build an individualized risk prediction nomogram for risk stratification and early clinical intervention to reduce mortality. Methods. In this retrospective study, the clinical characteristics of 382 confirmed COVID-19 patients, consisting of 108 with and 274 without preexisting T2D, from January 8 to March 7, 2020, in Tianyou Hospital in Wuhan, China, were collected and analyzed. Univariate and multivariate Cox regression models were performed to identify specific clinical factors associated with mortality of COVID-19 patients with T2D. An individualized risk prediction nomogram was developed and evaluated by discrimination and calibration. Results. Nearly 15% (16/108) of hospitalized COVID-19 patients with T2D died. Twelve risk factors predictive of mortality were identified. Older age (HR = 1.076, 95% CI = 1.014–1.143, p=0.016), elevated glucose level (HR = 1.153, 95% CI = 1.038–1.28, p=0.0079), increased serum amyloid A (SAA) (HR = 1.007, 95% CI = 1.001–1.014, p=0.022), diabetes treatment with only oral diabetes medication (HR = 0.152, 95%CI = 0.032–0.73, p=0.0036), and oral medication plus insulin (HR = 0.095, 95%CI = 0.019–0.462, p=0.019) were independent prognostic factors. A nomogram based on these prognostic factors was built for early prediction of 7-day, 14-day, and 21-day survival of diabetes patients. High concordance index (C-index) was achieved, and the calibration curves showed the model had good prediction ability within three weeks of COVID-19 onset. Conclusions. By incorporating specific prognostic factors, this study provided a user-friendly graphical risk prediction tool for clinicians to quickly identify high-risk T2D patients hospitalized for COVID-19.

At present, the global incidence of diabetes has increased in countries with large populations, and the changes in developing regions are particularly worthy of attention. In the past 40 years or so, the income situation in China, India, and other countries has exploded, leading to changes in the way of life and work as well as an increase in the prevalence of diabetes. Metabolic disorders caused by diabetes can lead to secondary vascular complications, which have long-term malignant effects on the heart, kidneys, brain, and other vital organs of patients. Adequate primary prevention measures are needed to reduce the incidence of diabetic vascular complications, and more attention should be given to treatment after the disease. To this end, it is necessary to determine a standardized drug and physical therapy system and to build a more efficient and low-cost chronic disease management system.

Summary: We utilize polymer micelle to precisely control indocyanine green (ICG) J-aggregation in a fast and highly efficient way. In addition to simple encapsulation, the polymer micelle plays a role as a host template to drive ICG J-aggregation by the synergy of electrostatic and hydrophobic attractions. We further demonstrate that, due to the robust host-guest interaction, the intact of ICG J-aggregate will be secured by the polymer encapsulation during the intracellular and in vivo incubation. These features make this hierarchical assembly between ICG J-aggregate and the micelle polymer a promising biomedicine for cancer phototheranostics. Therefore the complex micelles are further modified by introduction of doxorubicin for chemotherapy and DNA aptamer for tumor targeting, and the final multi-functional micellar medicine shows high therapeutic efficacy for tumor, i.e., the tumor can be completely eliminated with no local reoccurrence and without long-term toxicity or side effects during a 24-day period after the treatment. : Medical Imaging; Organic Chemistry; Materials Science Subject Areas: Medical Imaging, Organic Chemistry, Materials Science

The miniaturization of transistors and the high density of integrated circuits makes conventional transistors reach a size limit, causing leakage currents, unstable performance, and increasing production cost. Spin field effect transistors (SFETs) based on spintronics use electron spin as an information carrier and regulate electron spin degree of freedom for storing and processing information. As a class of spintronics, Rashba spin–orbit coupling (SOC) effect attracts increasing attention because of its electric tunability. SFETs based on Rashba SOC and two-dimensional materials will make a qualitative leap in future semiconductor devices. Based on first-principles calculations, it is found that the applied strains along zigzag (ZZ), armchair (AC), and biaxial direction make the bandgaps of SnS and SnSe monolayers (ML) have an indirect-direct-zero transition. SnS and SnSe ML have a more stable electron spin and stronger Rashba spin splitting than InGaAs/InAlAs heterojunction and Au(111) surface. For SnS ML, 6% tensile strain along ZZ direction not only stabilizes the electron spin but also strengthens Rashba spin splitting to a maximum of 0.76 eV Å. For SnSe ML, 2% tensile strain along biaxial direction makes Rashba spin splitting strength reach a maximum of 1.33 eV Å.

Carborane encapsulation was visualized by using fluoroboropyrrole (BODIPY) zwitterionic polymer as fluorescence marker. Firstly, a water-soluble fluorescent probe carrier was prepared by combining the BODIPY derivatives with poly (carboxybetaine methacrylate) (p-CBMA). Two oil-in-water carborane polymers were self-assembled in organic solvents by means of dual ion hydrogen bonding. The ultraviolet and fluorescence spectra were measured with different organic solvents, and the spectra ranged from 531 to 555 nm. The dynamic self-assembly effect was tested by TEM, and the internal microscopic phenomena of the water-soluble polymer were further observed. It was confirmed that two kinds of BODIPY zwitterionic polymers were firmly encase the fat-soluble carborane, forming an oval shape. Carboranes are water-soluble, can achieve biocompatible expression, and can visualize the degree of aggregation in the targeted cells through its own fluorescence effect. Subsequent imaging of the cells showed that both polymers entered the targeted cells.

The morphology and morphogenesis of Pseudosincirra longicirrata nov. gen. and nov. comb., isolated from southern China, were investigated with living observation and protargol staining. Our population is similar to the original population in living characteristics and ciliary patterns. The main determinable morphogenetic features of P. longicirrata nov. comb. are the presence of five frontoventral-transverse cirral anlagen (FVT-anlagen) and a dorsomarginal kinety anlage. According to the origin of FVT-anlagen IV and V in proter, it can be determined that P. longicirrata nov. comb. possesses two frontoventral rows and one right marginal row. Hence, a new genus, Pseudosincirra nov. gen., is proposed, and the diagnosis of P. longicirrata nov. comb. is improved. The new genus is diagnosed as follows: adoral zone of membranelles and undulating membranes is in a Gonostomum pattern; there are three enlarged frontal cirri, one buccal cirrus, and one parabuccal cirrus; postperistomial cirrus and transverse cirri are lacking; there are two more or less long frontoventral rows and one right and two or more left marginal rows; cirri within all rows very widely spaced; dorsal kinety pattern is of Urosomoida type, that is, three dorsal kineties and one dorsomarginal kinety; and caudal cirri are present. Phylogenetic analyses based on the small subunit ribosomal (SSU rDNA) sequence data indicate that P. longicirrata nov. comb. clusters with Deviata and Perisincirra. It is considered that Pseudosincirra nov. gen. and Perisincirra paucicirrata should be assigned to the family Deviatidae; fine cirri, and cirri within all rows being relatively widely spaced, should be considered as plesiomorphies of Deviatidae; and Deviatidae is closely related to Dorsomarginalia or Strongylidium–Hemiamphisiella–Pseudouroleptus.

Diabetes is a complex metabolic disease characterized by hyperglycemia. Its complications are various, often involving the heart, brain, kidney, and other essential organs. At present, the number of diabetic patients in the world is growing day by day. The cardiovascular disease caused by diabetes has dramatically affected the quality of life of diabetic patients. It is the leading cause of death of diabetic patients. Diabetic patients often suffer from microvascular angina pectoris without obstructive coronary artery disease. Still, there are typical ECG ischemia and angina pectoris, that is, chest pain and dyspnea under exercise. Unlike obstructive coronary diseases, nitrate does not affect chest pain caused by coronary microvascular angina in most cases. With the increasing emphasis on diabetic microvascular angina, the need for accurate diagnosis of the disease is also increasing. We can use SPECT, PET, CMR, MCE, and other methods to evaluate coronary microvascular function. SPECT is commonly used in clinical practice, and PET is considered the gold standard for non-invasive detection of myocardial blood flow. This article mainly introduces the research progress of these imaging methods in detecting microvascular angina in diabetic patients.

Currently, boron neutron capture therapy（BNCT） is the most innovative and promising highly selective targeted radiotherapy for cancer. Therefore, this paper designed and synthesized two kinds of boron-polymers, wrapped in the same fluorophore -BODIPYs, as fluorescent targeting markers for rapid, accurate, real-time, and inexpensive detection of boron-containing drugs. The spherical polymer o-carborane (PBC) in different polar solvents, the ultraviolet maximum absorption wavelength is in the range of 530–545 nm. The maximum ultraviolet absorption wavelength of PBD is in the range of 440–520 nm. The fluorescence spectra of the two boron-polymer are very similar, and the maximum emission wavelength is concentrated in the range of 550–560 nm. In terms of cytotoxicity and in vitro cell imaging, the in vitro biological toxicity evaluation of the two boron-polymer reached the expected high level, especially the cytotoxic concentration of PBD reached 1.347 ± 0.033 μM, which was higher than the 2.829 ± 0.351 μM of PBC. By transmission electron microscopy, it was found that the two terminal zwitterions of BODIPY polymer tightly wrapped boron clusters to form small particle nanoclusters. The imaging of the two boron-polymers was tested in the Hera cell lines of low, medium, and high densities. The in vitro study results revealed high levels of accumulation in HeLa cells with higher cytotoxicity and boron uptake compared to L-boron-phenylalanine (BPA). In vivo imaging, large number of borane polymers were observed to accumulate in the subcutaneous tumor sites of mice over time, indicating that it has high selectivity and high aggregation.

Cardiovascular diseases (CVDs) are major causes of mortality and morbidity in the modern society. The rupture of atherosclerotic plaque can induce thrombus formation, which is the main cause of acute cardiovascular events. Recently, many studies have demonstrated that there are some relationships between microbiota and atherosclerosis. In this review, we will focus on the effect of the microbiota and the microbe-derived metabolites, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and lipopolysaccharide (LPS), on the stability of atherosclerotic plaque. Finally, we will conclude with some therapies based on the microbiota and its metabolites.

Ciliated protists (ciliates) are extremely diverse and play important ecological roles in almost all kinds of habitats. In this study, two new hypotrichs, Wilbertophrya sinica n. g. and n. sp. and Bakuella xianensis n. sp., from China are investigated. Wilbertophrya n. g. can be separated from related genera mainly by the combination of lacking a buccal cirrus, pretransverse cirri, and caudal cirri, while possessing frontoterminal cirri. Analyses based on morphological and molecular data confirm the validity of the species, W. sinica n. sp., which is characterized as follows: body 50–115 μm × 15–35 μm in vivo; midventral complex comprises four or five cirral pairs only and terminates above mid-body; three frontal, two frontoterminal cirri, and two to four transverse cirri; about 15 macronuclear nodules; colorless cortical granules sparsely distributed. Another new species, B. xianensis n. sp., was isolated from a freshwater wetland and is defined as follows: body 115–150 μm × 40–65 μm in vivo; about 70 macronuclear nodules; dark-brownish cortical granules in groups; midventral complex comprises 8–12 cirral pairs forming a row that terminates posteriorly in mid-body region and two or three short midventral rows that are continuous with the row of midventral pairs; three frontal, four to six frontoterminal, and three to five fine transverse cirri; three bipolar dorsal kineties. Phylogenetic analyses based on small subunit ribosomal DNA (SSU rDNA) sequence data suggest that the new genus Wilbertophrya n. g. belongs to an isolated clade, which might represent an undescribed taxon at the family level, whereas B. xianensis n. sp. groups with several congeners and members of other related genera are within the core urostylids.

The morphology and the regulation of cortical pattern associated with the cell size, division, and phylogenetic position of a new hypotrichous ciliate, Quadristicha subtropica n. sp. collected from a freshwater pond in southern China, were investigated. Quadristicha subtropica n. sp. is characterized as follows: size in vivo 60–115 μm × 25–45 μm; 19–21 adoral membranelles; buccal cirrus near anterior end of endoral and paroral; cirrus IV/3 at about level of buccal vertex; right marginal row begins ahead of buccal vertex; 11–16 right and 12–19 left marginal cirri; and dorsal cilia about 5 μm long. The basic morphogenetic process in Q. subtropica n. sp. is consistent with that of the type species, Quadristicha setigera. Phylogenetic analyses based on small subunit ribosomal DNA sequence data reveal that the systematic position of Q. subtropica n. sp. is rather unstable with low support values across the tree and the genus Quadristicha is not monophyletic.

Tyrosine kinase inhibitors (TKI)-resistant renal cancer is highly susceptible to metastasis, and enhanced vascular permeability promotes the process of metastasis. To evaluate the effect of cancer-derived exosomes on vascular endothelial cells and clarify the mechanism of metastasis in TKI-resistant renal cancer, we studied the crosstalk between clear cell renal cell carcinoma (ccRCC) cells and human umbilical vein endothelial cells (HUVECs). Exosomes from ccRCC cells enhanced the expression of vascular permeability-related proteins. Compared with sensitive strains, exosomes from resistant strains significantly enhanced vascular endothelial permeability, induced tumor angiogenesis and enhanced tumor lung metastasis in nude mice. The expression of miR-549a is lower in TKI-resistant cells and exosomes, which enhanced the expression of HIF1α in endothelial cells. In addition, TKI-resistant RCC cells reduced nuclear output of pre-miR-549a via the VEGFR2-ERK-XPO5 pathway, and reduced enrichment of mature miR-549a in cytoplasm, which in turn promoted HIF1α expression in RCC, leading to increased VEGF secretion and further activated VEGFR2 to form a feedback effect. miR-549a played an important role in the metastasis of renal cancer and might serve as a blood biomarker for ccRCC metastasis and even had the potential of becoming a new drug to inhibit TKI-resistance.

Actinomycetes play a vital role as one of the most important natural resources for both pharmaceutical and agricultural applications. The actinomycete strain SPRI-371, isolated from soil collected in Jiangsu province, China, was classified as Streptomyces aureus based on its morphological, physiological, biochemical and molecular biological characteristics. Its bacterial activity metabolites were identified as aureonuclemycin (ANM), belonging to adenosine derivatives with the molecular formula C16H19N5O9 for ANM A and C10H13N5O3 for ANM B. Simultaneously, the industrial fermentation process of a mutated S. aureus strain SPRI-371 was optimized in a 20 m3 fermentation tank, featuring a rotation speed of 170 rpm, a pressure of 0.05 MPa, an inoculum age of 36–40 h and a dissolved oxygen level maintained at 1–30% within 40–80 h and at >60% in the later period, resulting in an ANM yield of >3700 mg/L. In the industrial separation of fermentation broth, the sulfuric acid solution was selected to adjust pH and 4# resin was used for adsorption. Then, it was resolved with 20% ethanol solution and concentrated in a vacuum (60–65 °C), with excellent results. Antibacterial experiments showed that ANM was less active or inactive against Xanthomonas oryzae pv. oryzae, Xanthomonas citri subsp. citri and Xanthomonas oryzae pv. oryzicola and most bacteria, yeast and fungi in vitro. However, in vivo experiments showed that ANM exhibited extremely significant protective and therapeutic activity against diseases caused by X. oryzae pv. oryzae and X. oryzae pv. oryzicola in rice and X. citri in oranges and lemons. In field trials, ANM A 150 gai/ha + ANM B 75 gai/ha exhibited excellent therapeutic activity against rice bacterial leaf blight, citrus canker and rice bacterial leaf streak. Furthermore, as the dosage and production cost of ANM are lower than those of commercial drugs, it has good application prospects.

The challenge of eradicating cancer is that cancer cells possess diverse mechanisms to protect themselves from clinical strategies. Recently, ferroptosis has been shown to exhibit appreciable anti-tumor activity that could be harnessed for cancer therapy in the future. Ferroptosis is an iron-dependent form of regulated cell death that is characterized by the oxidization of polyunsaturated fatty acids (PUFAs) and accumulation of lipid peroxides. Ferroptosis has been closely correlated with numerous biological processes, such as amino acid metabolism, glutathione metabolism, iron metabolism, and lipid metabolism, as well as key regulators including GPX4, FSP1, NRF2, and p53. Although ferroptosis could be involved in killing various cancer cells, multiple aspects of this phenomenon remain unresolved. In this review, we summarize the biochemistry and biology of ferroptosis in diverse cancers and discuss the potential mechanisms of ferroptosis, which might pave the way for guiding cancer therapeutics.

The oncogene c-Jun is activated by Jun N-terminal kinase (JNK). Exosomes are nanometer-sized membrane vesicles released from a variety of cell types, and are essential for cell-to-cell communication. By using specific JNK inhibitor SP600125 or CRISPR/Cas9 to delete c-Jun, we found that exosomes from SP600125-treated A549 cancer cells (Exo-SP) or from c-Jun-KO-A549 cells (Exo-c-Jun-KO) dramatically inhibited tube formation of HUVECs. And the miR-494 levels in SP600125 treated or c-Jun-KO A549 cells, Exo-SP or Exo-c-Jun-KO, and HUVECs treated with Exo-SP or Exo-c-Jun-KO were significantly decreased. Meanwhile, Exo-SP and Exo-c-Jun-KO enhanced expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Addition of miR-494 agomir in Exo-c-Jun-KO treated HUVECs inhibited PTEN expression and promoted tube formation, suggesting the target of miR-494 might be PTEN in HUVECs. Moreover, A549 tumor xenograft model and Matrigel plug assay demonstrated that Exo-c-Jun-KO attenuated tumor growth and angiogenesis through reducing miR-494. Taken together, inhibition of c-Jun in A549 cancer cells exhibited antiangiogenic activity in vitro and in vivo through exosome/miRNA-494-3p/PTEN signal pathway.

Vascular calcification is the transformation of arterial wall mesenchymal cells, particularly smooth muscle cells (SMCs), into osteoblast phenotypes by various pathological factors. Additionally, vascular transformation mediates the abnormal deposition of calcium salts in the vascular wall, such as intimal and media calcification. Various pathological types have been described, such as calcification and valve calcification. The incidence of vascular calcification in patients with diabetes is much higher than that in nondiabetic patients, representing a critical cause of cardiovascular events in patients with diabetes. Because basic research on the clinical transformation of vascular calcification has yet to be conducted, this study systematically expounds on the risk factors for vascular calcification, vascular bed differences, sex differences, ethnic differences, diagnosis, severity assessments, and treatments to facilitate the identification of a new entry point for basic research and subsequent clinical transformation regarding vascular calcification and corresponding clinical evaluation strategies.

Morphogenesis of ciliated protists attracts a lot of attention, because their huge morphological diversity is related to formation of ciliary structures during cell division. In the present work, the morphology and morphogenesis as well as the phylogenetic position of a new, marine hypotrich ciliate, Nothoholosticha luporinii n. sp., were investigated. The new species is characterized by having a combination of the following features: a bicorona whose anterior row contains four frontal cirri and posterior row includes only two cirri, a single buccal cirrus, midventral complex composed of about 30 cirral pairs, one pretransverse cirrus, 3–6 transverse cirri, one left and one right marginal cirral row; three bipolar dorsal kineties; contractile vacuole located in about 2/3 of the body length, two types of cortical granules, and many macronuclear nodules scattered throughout the cytoplasm. The morphogenesis of N. luporinii follows the ontogenetic mode of Pseudokeronopsis, a well-known and closely related genus except that the macronucleus fuses into a single mass in the middle fission stage. Phylogenetic analyses based on the rDNA operon classify Nothoholosticha in the family Pseudokeronopsidae and support the distinctness of the new taxon as well as the monophyletic origin of the subfamily Nothoholostichinae.

Outlier detection is an important research direction in the field of data mining. Aiming at the problem of unstable detection results and low efficiency caused by randomly dividing features of the data set in the Isolation Forest algorithm in outlier detection, an algorithm CIIF (Cluster-based Improved Isolation Forest) that combines clustering and Isolation Forest is proposed. CIIF first uses the k-means method to cluster the data set, selects a specific cluster to construct a selection matrix based on the results of the clustering, and implements the selection mechanism of the algorithm through the selection matrix; then builds multiple isolation trees. Finally, the outliers are calculated according to the average search length of each sample in different isolation trees, and the Top-n objects with the highest outlier scores are regarded as outliers. Through comparative experiments with six algorithms in eleven real data sets, the results show that the CIIF algorithm has better performance. Compared to the Isolation Forest algorithm, the average AUC (Area under the Curve of ROC) value of our proposed CIIF algorithm is improved by 7%.

Non-alcoholic fatty liver disease (NAFLD) has become a common chronic disease in the world. NAFLD is not only a simple intrahepatic lesion, but also affects the occurrence of a variety of extrahepatic complications. In particular, cardiovascular complications are particularly serious, which is the main cause of death in patients with NAFLD. To study the relationship between NAFLD and AS may be a new way to improve the quality of life in patients with NAFLD. As we all known, inflammatory response plays an important role in the occurrence and development of NAFLD and AS. In this study, we found that the accumulation of Nε-carboxymethyllysine (CML) in the liver leads to hepatic steatosis. CML can induce the expression of interleukin (IL-1β), interleukin (IL-6), tumor necrosis factor (TNF-α), C-reactionprotein (CRP) by binding with advanced glycosylation end-product receptor (RAGE) and accelerate the development of AS. After silencing RAGE expression, the expression of pro-inflammatory cytokines was inhibited and liver and aorta pathological changes were relieved. In conclusion, CML/RAGE signal promotes the progression of non-alcoholic fatty liver disease and atherosclerosis. We hope to provide new ideas for the study of liver vascular dialogue in multi organ communication.

Despite the numerous studies on the large-scale patterns of species richness, the spatial variation and determinants of species richness for the alpine plants are still an outstanding question and critical to future biodiversity conservation. The genus Saxifraga is a typical alpine plant group with high species richness in the Himalaya-Hengduan Mountain (HHM) regions, China. We performed simple regression models and variance partitioning to assess the importance of different factors, especially soil-related ones, in driving Saxifraga richness patterns. The results showed that environmental energy, habitat heterogeneity, and soil heterogeneity together dominated the spatial variation of species richness. The coarse fragment volume (CRFVOL) of soil, elevation range, and soil heterogeneity are positively related to Saxifraga richness. Soil slightly outperforms habitat heterogeneity in predicting the spatial variation of Saxifraga species richness with an explanatory power of 39.3% and 36.6%, respectively. Environmental energy, such as the maximum temperature of the warmest quarter, is negatively correlated with species richness and explains 44.8% of spatial variation of Saxifraga richness. Multiple regression models, including three variables, each representing energy, soil, and habitat heterogeneity, can only explain 53.1% variation of species richness. Variance partitioning outscored 26% of the shared effects of the three variables, while the independent effect of each variable is less than 10%. These results indicated that the energy, soil, and habitat heterogeneity together are primary determinants of the spatial variation of Saxifraga species richness. However, there are probably other hidden factors predicting species richness variation due to the low explanatory power of the multiple regression models. Our study emphasizes the significance of soil properties in determining species richness patterns in China, especially for alpine plant groups. The negative association of species richness with temperature suggests a potential threat of alpine biodiversity loss in HHM from future warming.

Vascular calcification is an abnormal cell-mediated process in which bone-specific hydroxyapatite crystals are actively deposited on the blood vessel wall and is a significant pathological basis for the increased incidence and mortality of adverse cardiovascular events. Macrophages play an important regulatory role in the occurrence, development, and regression of vascular calcification. After the tissue microenvironment changes, macrophages subsequently change their polarity and phenotype or secrete functional substances as an adaptive response. As research on macrophages continue to move into this field, we gain a new understanding of the mechanism of the formation and regression of vascular calcification, which might offer valuable new intervention targets for the prevention and inhibition of vascular calcification. This review summarizes a wealth of research in this field and explores the roles of macrophages in the development process of vascular calcification.

Background. Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. Nε-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic atherosclerosis is unknown. Methods and Results. In this study, we used anterior tibiofibular vascular samples from diabetic foot amputation patients and accident amputation patients, and histological and cytological tests were performed using a diabetic ApoE-/- mouse model and primary peritoneal macrophages, respectively. The results showed that the atherosclerotic plaques of diabetic foot amputation patients and diabetic ApoE-/- mice were larger than those of the control group. Inhibition of the Vav1/Rac1 pathway reduced vascular plaques and promoted the migration of macrophages to lymph nodes. Transwell and wound healing assays showed that the migratory ability of macrophage-derived foam cells was inhibited by CML. Cytoskeletal staining showed that advanced glycation end products inhibited the formation of lamellipodia in foam cells, and inhibition of the Vav1/Rac1 pathway restored the formation of lamellipodia. Conclusion. CML inhibits the migration of foam cells from blood vessels via the Vav1/Rac1 pathway, and this process affects the formation of lamellipodia.

Background. Advanced glycation end products play an important role in diabetic atherosclerosis. The effects of advanced glycation end products (AGEs) on vascular smooth muscle cell- (VSMC-) derived foam cell formation and phenotypic transformation are unknown. Methods. Serological and histological samples were obtained from diabetic amputation patients and accident amputation patients from the Affiliated Hospital of Jiangsu University. CD68/Actin Alpha 2 (ACTA2) coimmunofluorescence sections were used to quantify the number of VSMCs with macrophage-like phenotypes. Western blotting was used to detect the expression of the receptor of advanced glycation end products in vascular samples. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the level of serum Nε-carboxymethyl-lysine (CML). In vitro oil red O staining was used to examine lipid accumulation in VSMCs stimulated by CML. The expression of VSMCs and macrophage markers was measured by western blotting and quantitative real-time PCR. Furthermore, changes in VSMC migration and secretion were detected by the Transwell assay and ELISA. Results. In the arterial plaque sections of diabetic patients, VSMCs transformed to a macrophage-like phenotype. The serum CML and RAGE levels in the plaques were significantly higher in the diabetes group than those in the healthy control group and were significantly related to the number of macrophage-like VSMCs. CML stimulation promoted intracellular lipid accumulation. However, CML stimulation decreased the expression of VSMC markers and increased the expression of macrophage phenotype markers. Finally, CML promoted smooth muscle cell migration and the secretion of proinflammatory-related factors. Conclusions. CML induces VSMC-derived foam cell formation, and VSMCs transdifferentiate to a macrophage-like state, which may be mediated by the activation of RAGE.

Abstract Background Primary hepatic sarcomatous carcinoma (PHSC) is a rare malignancy composed of both carcinomatous (either hepatocellular or cholangiocellular) and sarcomatous components. The purpose of our study was to evaluate the imaging and clinical findings of PHSCs, improving the understanding and diagnosis of tumors. Methods We retrospectively reviewed the imaging and clinical findings of ten patients with pathologically proven PHSCs, including two cases of sarcomatous intrahepatic cholangiocarcinoma (S-ICC), seven cases of sarcomatous hepatocellular carcinoma (S-HCC) and one case of sarcomatous combined hepatocellular and cholangiocarcinoma (S-HCC–CC). Six patients underwent computed tomography (CT) scans and five underwent magnetic resonance imaging (MRI) scans with one of them having both CT and MRI scans. Results Eight of ten patients had a background of chronic hepatitis or cirrhosis. The elevation of alpha-fetoprotein (AFP) was positive in half of the patients. All the tumors were located near the liver subcapsular area and six of ten cases were massive with round or oval shapes and ill-defined. The lesion textures were mainly heterogeneous in eight tumors for the necrosis or hemorrhage. Eight tumors showed hypo-enhancement and nine tumors exhibited initial peripheral rim (five cases) or heterogeneous (four cases) enhancement, followed by progressive (six cases) and peripheral or partial washout (three cases) on the later phases. Of the seven surgically resected tumors, five showed liver capsular invasion with one of them rupturing into the perihepatic space. Vascular thrombosis (five cases), intrahepatic metastasis (four cases), adjacent organ invasion or seeding (three cases), and lymph node metastasis (four cases) were found on imaging or in pathology. The follow-up period ranged from one to 36 months. Four patients with T3-T4 staging died from recurrence and metastasis between 2 and 5 months, and three patients with T1 staging did not have any recurrence between 16 and 24 months. Conclusion PHSC generally presents as a subcapsular mass with hypovascularity and may be characterized by rim-like or heterogeneous enhancement on the arterial phase and a progressive dynamic pattern. These tumors usually coincide with chronic hepatitis or cirrhosis and poor prognosis appears to be associated with TNM staging.

Abstract The 5‐year survival rate decreases rapidly once the prostate cancer has invaded distant organs, although patients with localized prostate cancer have a good prognosis. In recent years, increasing numbers of reports showed that circulating tumor cells (CTCs) may play an important role in tumor metastasis and they have stronger potential of invasion and migration compared with their parental cells. In our previous investigation, we isolated CTCs from prostate cancer cell lines PC3. In this study, we found a novel antimetastasis gene NDR1 by analyzing different gene expression between CTCs and PC3. Lower NDR1 gene and protein expression were found in both prostate cancer cell lines and clinical specimens. Besides, NDR1 function acting as metastasis inhibitor was discovered both in vitro and in vivo. Further, we also discovered that several epithelial‐mesenchymal transition (EMT)‐related genes were upregulated when decreased NDR1 in PC3 cell lines. Therefore, our results revealed a role of NDR1 in the suppression of prostate cancer cell metastasis and provided a potential mechanism of action, thus offering new therapeutic strategies against prostate cancer metastasis.

The effects of cyclic heat treatment and hot deformation on the spheroidization and orientation of the TC17 titanium alloy were investigated using a light microscope (LM) and electron backscattered diffraction (EBSD). The experimental results indicate that in the two-phase temperature range of a simple, cycle heat treatment, the spheroidization of the lamellar microstructure of the TC17 titanium alloy is finite. After cyclic heat treatment and compression deformation, the Widmannstatten structure disappears, the spheroidized α lamellae is more obvious, but the uniformity of its orientation is not greatly improved. In addition, the recrystallization velocity, and the strength and toughness of the two phases in deformation lead to a difference in their orientation, and the recrystallization velocity of the α phase is faster than that of the β phase. In the deformation process, the anisotropy of the α phase is preferentially reduced. On the other hand, during the hot deformation process, the degree of deformation of the α phase is lower than that of the β phase, because the α phase is harder than the β phase. The strain is primarily concentrated on the softer β phase adjacent to α phase, which produces greater uniformity in α phase than in the β phase.

Abstract Biomarkers are measurable changes associated with the disease. Urine can reflect the changes of the body while blood is under control of the homeostatic mechanisms; thus, urine is considered an important source for early and sensitive disease biomarker discovery. A comprehensive profile of the urinary proteome will provide a basic understanding of urinary proteins. In this paper, we present an in-depth analysis of the urinary proteome based on different separation strategies, including direct one dimensional liquid chromatography–tandem mass spectrometry (LC/MS/MS), two dimensional LC/MS/MS, and gel-eluted liquid fraction entrapment electrophoresis/liquid-phase isoelectric focusing followed by two dimensional LC/MS/MS. A total of 6085 proteins were identified in healthy urine, of which 2001 were not reported in previous studies and the concentrations of 2571 proteins were estimated (spanning a magnitude of 106) with an intensity-based absolute quantification algorithm. The urinary proteins were annotated by their tissue distribution. Detailed information can be accessed at the “Human Urine Proteome Database” (www.urimarker.com/urine).

Branched-chain amino acids catabolism plays an important role in human cancers. Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females, and the new global incidence is over 1.2 million cases. The branched-chain α-keto acid dehydrogenase kinase (BCKDK) is a rate-limiting enzyme in branched-chain amino acids catabolism, which plays an important role in many serious human diseases. Here we investigated that abnormal branched-chain amino acids catabolism in colorectal cancer is a result of the disease process, with no role in disease initiation; BCKDK is widely expressed in colorectal cancer patients, and those patients that express higher levels of BCKDK have shorter survival times than those with lower levels; BCKDK promotes cell transformation or colorectal cancer ex vivo or in vivo. Mechanistically, BCKDK promotes colorectal cancer by enhancing the MAPK signaling pathway through direct MEK phosphorylation, rather than by branched-chain amino acids catabolism. And the process above could be inhibited by a BCKDK inhibitor, phenyl butyrate.

Advanced glycation end products (AGEs) are closely associated with diabetic macrovascular complications. The present study aimed to investigate the effects of Nε-Carboxymethyl-Lysine (the key active component of AGEs) in diabetic atherosclerosis on foam cell apoptosis and to explore the underlying mechanisms. Tissue sections were collected from 12 Type 2 diabetic patients and 4 control patients who underwent amputation surgery following a car accident. Peritoneal injection of streptozotocin in ApoE−/− mice was used to generate a diabetic model in vivo, and Raw 264.7 cells treated with CML and 740Y-P (a PI3K/AKT signaling agonist) were used to explore the effect of PI3K/AKT signaling in CML-induced foam cell apoptosis in vitro. The anterior tibial section of diabetic amputees contained a thinner fiber cap, higher lipid content, and more apoptotic cells than were found in control patients. in vitro studies using Raw 264.7 cell-derived foam cells and in vivo studies using diabetic ApoE-/- mice showed that CML levels dose-dependently reduced cell vitality, induced foam cell apoptosis and regulated apoptosis related protein. Furthermore, CML significantly decreased the phosphorylation of PI3K/AKT signaling, and restoration of PI3K/AKT signaling by 740Y-P decreased the CML-induced foam cell apoptosis. In conclusion, our results showed CML induced foam cell apoptosis in diabetic atherosclerosis through inhibiting the PI3K/AKT pathway.

[This corrects the article DOI: 10.1371/journal.pone.0133270.].

BACKGROUND: Despite the initial evidence supporting the utility of intravascular imaging to guide percutaneous coronary intervention (PCI), adoption remains low. Recent new trial data have become available. An updated study-level meta-analysis comparing intravascular imaging to angiography to guide PCI was performed. This study aimed to evaluate the clinical outcomes of intravascular imaging-guided PCI compared with angiography-guided PCI. METHODS AND RESULTS: A random-effects meta-analysis was performed on the basis of the intention-to-treat principle. The primary outcomes were major adverse cardiac events, cardiac death, and all-cause death. Mixed-effects meta-regression was performed to investigate the impact of complex PCI on the primary outcomes. A total of 16 trials with 7814 patients were included. The weighted mean follow-up duration was 28.8 months. Intravascular imaging led to a lower risk of major adverse cardiac events (relative risk [RR], 0.67 [95% CI, 0.55-0.82]; P

We previously reported the anti-inflammatory and anti-asthmatic activities of the extract of the Inula japonica Thunb. Aiming for discovery of a novel anti-inflammatory compound, we isolated spinacetin from the extract and investigated its in vitro and in vivo anti-inflammatory effect and the related mechanism. Effect of spinacetin on the Syk signaling pathway was studied in bone marrow-derived mast cells (BMMCs), and that on the nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) was investigated in Rat basophilic leukemia (RBL)-2H3 cells and human mast cell line (HMC-1). The in vivo anti-inflammatory activity was assessed with passive cutaneous anaphylaxis (PCA) reaction assay. Spinacetin significantly inhibited the release of histamine, and production of inflammatory mediators such as leukotriene C4 (LTC4) and interlukin-6 (IL-6) in IgE/Ag stimulated BMMCs. Analysis of the signaling pathways demonstrated that spinacetin inhibited activation of Syk, linker of activated T cells (LAT), phospholipase Cγ (PLCγ), cytosolic phospholipase A2 (cPLA2), MAPKs, Akt/NF-κB, and intracellular Ca2+ mobilization but with no effect on Fyn and Lyn. On the other hand, spinacetin suppressed IgE/Ag-induced activation of RBL-2H3 cells with inhibition against phosphorylation of extracellular signal regulated-protein kinase (ERK), c-Jun-NH2-terminal kinase (JNK), p38 MAPKs, PLCγ, translocation of cPLA2, and Akt/IκBα/NF-κB signal. However, spinacetin had no effect on PMA and A23187-induced activation of HMC-1. Furthermore, oral administration of spinacetin dose-dependently attenuated IgE/Ag-mediated PCA reaction in mouse model. Taken together, spinacetin showed the activities in preventing inflammatory processes, which might be at least partially attributed to the abolishment of Syk-dependent activation of IgE/Ag-mediated mast cells.

Nickel base and titanium base materials have been widely applied to engines in aerospace industry, and these engines are essential components of airplanes. The machining characteristics of aerospace materials may cause machining cutters to be worn down in a short time and thus reduce the accuracy of processing. The plasma-assisted machining adopted in the research is a kind of the complex machining method. In the cases of nickel base and titanium base alloys, the method can heat workpieces in an extremely short duration to soften the materials for the ease of cutting so that the cutting force, cutter wear, and machining cost will all be reduced. The research adopted plasma heating to soften parts of the materials and aimed to explore the heating of nickel base alloy. The temperature variation of the materials was investigated and measured by adjusting the current and feed velocity. Moreover, Inconel-718 superalloy was adopted for the comparison with nickel base alloy for the observation of the influence and change brought by heat, and the method of exponential smoothing was adopted to conduct the prediction and analysis of thermal diffusion for understanding the influence and change brought by electric current on nickel base materials. Finally, given the current from 20 A to 80 A and feed velocity from 1,000 mm/min to 3,000 mm/min, the influence of thermal diffusion was investigated and the related model was built.

Background. Vascular calcification is widespread and clinically significant, contributing to substantial morbidity and mortality. Calcifying vascular cells are partly derived from local vascular smooth muscle cells (VSMCs), which can undergo chondrogenic or osteogenic differentiation under inflammatory environment. Recently, we have found activation of CD137 signaling accelerated vascular calcification. However, the underlying mechanism remains unknown. This study aims to identify key mediators involved in CD137 signaling-induced vascular calcification in vivo and in vitro. Methods. Autophagy flux was measured through mRFP-GFP-LC3 adenovirus and transmission electron microscopy. Von Kossa assay and alkaline phosphatase (ALP) activity were used to observe calcification in vivo and in vitro, respectively. Autophagosome-containing vesicles were collected and identified by flow cytometry and Western blot. Autophagy or calcification-associated targets were measured by Western blot, quantitative real-time PCR, and immunohistochemistry. Results. Treatment with the agonist-CD137 displayed c-Jun N-terminal kinase- (JNK-) dependent increase in the expression of various markers of autophagy and the number of autophagosomes relative to the control group. Autophagy flux experiments suggested that agonist-CD137 blocked the fusion of autophagosomes with lysosomes in cultured VSMCs. Calcium deposition, ALP activity, and the expression of calcification-associated proteins also increased in agonist-CD137 group compared with anti-CD137 group, which could be recovered by autophagy stimulator rapamycin. Autophagosome-containing vesicles collected from agonist-CD137 VSMCs supernatant promoted VSMC calcification. Conclusion. The present study identified a new pathway in which CD137 promotes VSMC calcification through the activation of JNK signaling, subsequently leading to the disruption of autophagic flux, which is responsible for CD137-induced acceleration of vascular calcification.

Opisthotropis latouchii is an endemic species which inhabits flowing streams in China. In this study, the complete mitochondrial genome of O. latouchii was determined using high-throughput sequencing data. The mitogenome was 17,051 bp in length and contained 13 protein-coding genes, 22 transfer RNA, 2 ribosomal RNA and 2 control regions. The total nucleotide composition was 34.09% A, 25.35% T, 27.39% C, and 13.16% T, respectively. The phylogenetic analysis showed that O. latouchii was closely related with Nerodia sipedon in Colubridae.