Diagnosis and prognosis of breast cancer by high-performance serum metabolic fingerprints.

High-performance metabolic analysis is emerging in the diagnosis and prognosis of breast cancer (BrCa). Still, advanced tools are in demand to deliver the application potentials of metabolic analysis. Here, we used fast nanoparticle-enhanced laser desorption/ionization mass spectrometry (NPELDI-MS) to record serum metabolic fingerprints (SMFs) of BrCa in seconds, achieving high reproducibility and low consumption of direct serum detection without treatment. Subsequently, machine learning of SMFs generated by NPELDI-MS functioned as an efficient readout to distinguish BrCa from non-BrCa with an area under the curve of 0.948. Furthermore, a metabolic prognosis scoring system was constructed using SMFs with effective prediction performance toward BrCa (P < 0.005). Finally, we identified a biomarker panel of seven metabolites that were differentially enriched in BrCa serum and their related pathways. Together, our findings provide an efficient serum metabolic tool to characterize BrCa and highlight certain metabolic signatures as potential diagnostic and prognostic factors of diseases including but not limited to BrCa.

Maternal peripheral blood telomere length and preterm birth in African American women: a pilot study.

PURPOSE: This study aimed to explore the association between preterm birth and telomere length of maternal peripheral blood in African American women. METHODS: 78 African American women were recruited for this study between 2018 and 2023 from 2 prenatal clinics in central and east Texas. Participants provided blood samples and completed clinic questionnaires, with clinical data collected from their post-delivery medical records. Telomere length was measured using monochrome multiplex quantitative real-time polymerase chain reaction. Linear regression and multinomial logistic regression were used to analyze the association between telomere length and gestational length. Kruskal-Wallis's test and Fisher's exact test were used to compare preterm birth, early-term birth and full-term birth by telomere length, social-demographic characteristics, stress and discrimination. RESULTS: The rates of preterm birth was higher in pregnant women with shorter telomeres. After adjusting for confounders, for every 10-units increase in the relative telomere-to-single-copy gene (T/S) ratio, gestational days increased by 1.090 days (90% CI 0.182, 1.997), and for every 10-units decrease in the T/S ratio, the odds of preterm birth was 2.664 (90% CI 1.064, 6.673) times greater than the odds of full-term birth. No statistically significant associations were observed between stress, discrimination, and either preterm birth or telomere length. CONCLUSIONS: Maternal peripheral blood telomere shortening is associated with preterm birth, providing support to further explore the clinical utility of maternal telomere testing for prediction and early intervention of preterm birth and the study of biological mechanisms of spontaneous preterm birth.

Momordica charantia Is a Novel Host of 'Candidatus Phytoplasma malaysianum'-Related Strains Associated with Bitter Melon Stem Fasciation Disease in China.

Momordica charantia, also known as bitter melon, bitter gourd, and bitter squash, is a member of the Cucurbitaceae family and is widely grown in tropical and subtropical regions for its edible fruit and medicinal properties (Alves et al. 2017). In April 2022, bitter melon plants exhibiting stem fasciation and excessive tendril symptoms were observed in a 50-acre vegetable farm in Yijia Village, Weishan Yizu Huizu Autonomous County, Dali, Yunnan Province, China (Fig. 1). The farm primarily grew tomatoes, but around 400 bitter melon plants were planted in spots where tomatoes failed to establish. One plot had a 40% incidence rate, with four out of ten bitter melon plants showing symptoms. Scattered cases were observed in other plots, leading to an overall disease incidence rate of around 2% for the entire farm. Phytoplasma infection was suspected due to symptomatic plants growing in the same province as previously reported cases of phytoplasma diseases, such as happy tree (Camptotheca accuminata) witches'-broom disease, and the presence of phytoplasma-transmitting leafhoppers (Qiao et al. 2023). DNA was extracted from four symptomatic samples and two healthy controls collected from the abovementioned plot with a 40% disease incidence using Bioteke's Plant Genomic DNA Extraction Kit and then tested for phytoplasma infection. A nested PCR assay was conducted using primer pair P1/16S-SR followed by P1A/16S-SR to amplify the near full-length phytoplasma 16S rDNA (about 1.5kb) as previously described (Lee et al. 2004). None of the healthy controls tested positive for phytoplasma infection, while three out of four symptomatic plants showed positive results. The amplicons from the nested PCR were cloned into the pCRII-TOPO vector as previously described (Lee et al. 2004). The resulting clones were sequenced, and the representative sequence was deposited into GenBank (accession number PP489216). The iPhyClassifier (Zhao et al. 2009) was employed to determine the phytoplasma species and group/subgroup associated with the bitter melon stem fasciation (BMSF) disease. The results indicated that the diseased bitter melon plants were infected with a strain related to 'Candidatus Phytoplasma malaysianum' (EU371934), with a 98.07% sequence identity. The similarity coefficient was 1.00 compared to the reference strain of 16SrXXXII-D (GenBank accession: MW138004). The phytoplasma strain associated with BMSF disease was designated as BMSF1. In addition, the same DNA samples underwent further characterization of the BMSF strains. A nested PCR was conducted using primer pair rpL2F3/rpIR1A, followed by rp(III)-FN/rpIR1A to amplify a phytoplasma-specific rp gene segment (about 1.2 kb) (Martini et al. 2007; Davis et al. 2013). Three out of four samples tested positive, consistent with the 16S rRNA gene amplification results. Similarly, a primer pair L15F1/MapR1 followed by secYF1(III)/secYR1(III) was used to amplify a phytoplasma-specific partial spc operon (about 1.7 kb) that includes the complete secY gene and partial rpl15 and map genes, as previously described (Lee et al. 2010). The obtained rp and partial spc amplicons were cloned and sequenced (GenBank accession numbers PP464295 and PP464296). The rp and secY gene sequences were searched against the non-redundant nucleotide collection in the NCBI database using BLASTN. The top hit for the rp gene was 'Ca. Phytoplasma luffae' (CP054393), with 83.24% identity (1068/1283 base-matching). The top hit for the secY gene was also 'Ca. Phytoplasma luffae' (CP054393), with 72.53% identity (1294/1784 base-matching). The percent identity of the BMSF sequences compared to the top hit is low since no other group 16SrXXXII rp and secY gene sequences are available for comparison. A subgroup 16SrXXXII-D phytoplasma strain has been previously reported associated with Camptotheca acuminata witches'-broom (Qiao et al. 2023) and Trema tomentosa witches'-broom (Yu et al. 2021) in China. To our knowledge, bitter melon represents a new host of 'Candidatus Phytoplasma malaysianum'-related strains, and this is the first report of BMSF disease in China. The findings suggest that 'Candidatus Phytoplasma malaysianum'-related strains infect not only ornamental plants but also crops.

Genome-wide identification and characterization of polycomb repressive complex 2 core components in upland cotton (Gossypium hirsutum L.).

BACKGROUND: The evolutionarily conserved Polycomb Repressive Complex 2 (PRC2) plays a vital role in epigenetic gene repression by depositing tri-methylation on lysine residue K27 of histone H3 (H3K27me3) at the target loci, thus participating in diverse biological processes. However, few reports about PRC2 are available in plant species with large and complicated genomes, like cotton. RESULTS: Here, we performed a genome-wide identification and comprehensive analysis of cotton PRC2 core components, especially in upland cotton (Gossypium hirsutum). Firstly, a total of 8 and 16 PRC2 core components were identified in diploid and tetraploid cotton species, respectively. These components were classified into four groups, E(z), Su(z)12, ESC and p55, and the members in the same group displayed good collinearity, similar gene structure and domain organization. Next, we cloned G. hirsutum PRC2 (GhPRC2) core components, and found that most of GhPRC2 proteins were localized in the nucleus, and interacted with each other to form multi-subunit complexes. Moreover, we analyzed the expression profile of GhPRC2 genes. The transcriptome data and quantitative real-time PCR (qRT-PCR) assays indicated that GhPRC2 genes were ubiquitously but differentially expressed in various tissues, with high expression levels in reproductive organs like petals, stamens and pistils. And the expressions of several GhPRC2 genes, especially E(z) group genes, were responsive to various abiotic and biotic stresses, including drought, salinity, extreme temperature, and Verticillium dahliae (Vd) infection. CONCLUSION: We identified PRC2 core components in upland cotton, and systematically investigated their classifications, phylogenetic and synteny relationships, gene structures, domain organizations, subcellular localizations, protein interactions, tissue-specific and stresses-responsive expression patterns. Our results will provide insights into the evolution and composition of cotton PRC2, and lay the foundation for further investigation of their biological functions and regulatory mechanisms.

Highly accurate OAM mode detection network for ring Airy Gaussian vortex beams disturbed by atmospheric turbulence based on interferometry.

Atmospheric turbulence reduces the detection accuracy of orbital angular momentum (OAM) modes, which affects the performance of OAM optical communication. In this paper, we propose a method based on interferometry and a residual network (ResNet) to detect the OAM modes of ring Airy Gaussian vortex beams (RAGVBs) disturbed by atmospheric turbulence. The RAGVBs first interfere with spherical waves to obtain the sign features of the OAM modes, and then ResNet is employed to recognize OAM modes from the interferograms. The results demonstrate that the detection accuracy is higher than that of the OAM spectrum method under different turbulence strengths. The detection accuracy can even reach over 99% under strong fluctuations. Our research provides a reference for improving the performance of OAM optical communication through atmospheric turbulence.

Investigation of the clinical effects of acipimox in patients with vulnerable carotid atherosclerosis.

OBJECTIVE: To investigate the clinical effects of acipimox in patients with vulnerable carotid atherosclerosis. METHODS: 80 patients with vulnerable carotid atherosclerosis who were admitted to the Department of Cardiology in Wuxi Second People's Hospital between February 2020 and October 2021 were enrolled in this study. All of these patients were randomly divided into an observation group (n = 40), who were given acipimox and conventional treatment, and a control group (n = 40), who were given conventional treatment. The levels of blood lipids and adiponectin (APN), the carotid intima-media thickness (IMT), the area, thickness and number of CAS, peak systolic velocities (PSV) and end-diastolic blood velocity (EDV) of common carotid artery (CCA), and the level of inflammatory markers were measured and compared between the two groups pretherapy and posttreatment. Then, the adverse events were collected and compared between the two groups posttreatment. RESULTS: The demographics and basic clinical characteristics were not significantly different between the two groups. At posttreatment, the levels of TC, LDL-C, ANP, IL-6, TNF-α and hs-CRP in the observation group were significantly lower than those in the control group at posttreatment. Moreover, the IMT and the area and thickness of CAS in the observation group were significantly lower than those in the control group. After treatment, PSV was lower and EDV was higher in two groups than before treatment; after treatment, compared with control group, PSV in observation group was lower, while EDV was higher. Most importantly, the rate of adverse events was similar in the two groups. CONCLUSIONS: Acipimox reduced the blood lipid levels in patients with vulnerable carotid atherosclerosis. It also stabilized vulnerable plaques and reduced CAS.

Marrow Mesenchymal Stem Cell-Derived Exosomes Upregulate Astrocytic Glutamate Transporter-1 Expression via miR-124/mTOR Pathway against Oxygen-Glucose Deprivation/Reperfusion Injury.

BACKGROUND: Experimental investigations have reported the efficacy of marrow mesenchymal stem cell-derived exosomes (MSC-Exos) for the treatment of ischemic stroke. The therapeutic mechanism, however, is still unknown. The purpose of the study is to show whether MSC-Exos increases astrocytic glutamate transporter-1 (GLT-1) expression in response to ischemic stroke and to investigate further mechanisms. METHODS AND RESULTS: An in vitro ischemia model (oxygen-glucose deprivation/reperfusion, OGD/R) was used. MSC-Exos was identified by Western blot (WB) and transmission electron microscopy (TEM). To further investigate the mechanism, MSC-Exos, miR-124 inhibitor, and mimics, and a mTOR pathway inhibitor (rapamycin, Rap) were used. The interaction between GLT-1 and miR-124 was analyzed by luciferase reporter assay. The GLT-1 RNA expression and miR-124 was assessed by quantitative real-time polymerase chain reaction (qRTPCR). The protein expressions of GLT-1, S6, and pS6 were detected by WB. Results demonstrated that MSC-Exos successfully inhibited the decrease of GLT-1 and miR-124 expression and the increase of pS6 expression in astrocytes after OGD/R. miR-124 inhibitor suppressed the effect of MSC-Exos on GLT-1 upregulation after OGD/R. Rapamycin notably decreased pS6 expression with significantly higher GLT-1 expression in astrocytes injured by OGD/R. Luciferase activity of the reporter harboring the wild-type or mutant GLT-1 3'UTR was not inhibited by miR-124 mimics. Further results showed that the inhibiting effect of MSC-Exos on pS6 expression and promoting effect of MSC-Exos on GLT-1 expression could be reversed by miR-124 inhibitor after OGD/R; meanwhile, the above conditions could be reversed again by rapamycin. CONCLUSIONS: Results show that miR-124 and the mTOR pathway are involved in regulation of MSC-Exos on GLT-1 expression in astrocytes injured by OGD/R. miR-124 does not directly target GLT-1. MSC-Exos upregulates GLT-1 expression via the miR-124/mTOR pathway in astrocytes injured by OGD/R.

C-Terminal Truncated HBx Facilitates Oncogenesis by Modulating Cell Cycle and Glucose Metabolism in FXR-Deficient Hepatocellular Carcinoma.

Farnesoid X receptor (FXR) is a nuclear receptor known to play protective roles in anti-hepatocarcinogenesis and regulation of the basal metabolism of glucose, lipids, and bile acids. FXR expression is low or absent in HBV-associated hepatocarcinogenesis. Full-length HBx and HBx C-terminal truncation are frequently found in clinical HCC samples and play distinct roles in hepatocarcinogenesis by interacting with FXR or FXR signaling. However, the impact of C-terminal truncated HBx on the progression of hepatocarcinogenesis in the absence of FXR is unclear. In this study, we found that one known FXR binding protein, a C-terminal truncated X protein (HBx C40) enhanced obviously and promoted tumor cell proliferation and migration by altering cell cycle distribution and inducing apoptosis in the absence of FXR. HBx C40 enhanced the growth of FXR-deficient tumors in vivo. In addition, RNA-sequencing analysis showed that HBx C40 overexpression could affect energy metabolism. Overexpressed HSPB8 aggravated the metabolic reprogramming induced by down-regulating glucose metabolism-associated hexokinase 2 genes in HBx C40-induced hepatocarcinogenesis. Overall, our study suggests that C-terminal truncated HBx C40 synergizes with FXR deficiency by altering cell cycle distribution as well as disturbing glucose metabolism to promote HCC development.

Anomalous origin of the left coronary artery from the pulmonary artery as a rare cause of mitral valve prolapse: a case report.

BACKGROUND: Mitral valve prolapse (MVP) is an etiologically heterogeneous disorder. Early diagnosis and prompt treatment of the underlying disease are of great significance. Herein, we present a rare case of MVP caused by anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). CASE PRESENTATION: A 22-year-old female presented with a 16-year history of anterior mitral leaflet prolapse. However, she had never experienced any discomfort before. At a routine follow-up, a transthoracic echocardiogram showed anterior mitral leaflet prolapse (A2) with moderate mitral regurgitation, and a retrograde blood flow from an extremely dilated left coronary artery (LCA). Further coronary angiography and coronary computed tomography angiography confirmed the diagnosis of ALCAPA. She subsequently underwent successful LCA reimplantation and concomitant mitral valve replacement. Intraoperatively, her mitral annulus was mildly dilated, anterior mitral valve leaflet appeared markedly thickened with rolled edges, and a chordae tendineae connecting the anterior leaflet (A2) was ruptured and markedly shortened. CONCLUSIONS: ALCAPA is a rare and potentially life-threatening congenital coronary artery anomaly that may cause mitral valve prolapse. Echocardiogram is an important screening tool for this disorder.

Comparison of the biometric parameters in patients with high myopia and anisometropia.

BACKGROUND: To compare biometric parameters, especially lens parameters, in patients with high myopia and anisometropia. METHODS: Patients with spherical equivalent greater than -6D and at least one eye with an axial length greater than 26 mm and a difference in binocular axial length greater than 2 mm were included in this study. In each patient, the eye with a relatively shorter axial length was assigned to Group S, and the other eye was assigned to Group L. In patients whose binocular axial length difference was greater than 4 mm, the eye with the shorter axial length was assigned to Group S1 and the other eye was assigned to Group L1. In patients whose shorter eye axial was less than 26 mm, the eye with the shorter axial was assigned to Group S2 and the other eye was assigned to Group L2. Central corneal thickness, corneal curvature radius, axial length, anterior chamber depth, lens thickness, white-to-white corneal diameter and the radius of the anterior and posterior lens capsules were compared between Group S and Group L, Groups S1 and L1, and Groups S2 and L2. RESULTS: Sixty-four people were enrolled in the study. There were 26 people with an axial length difference more than 4 mm (Group S1 and Group L1) and 34 patients with an axial length less than 26 mm (Group S2 and Group L2). No significant differences were found in any parameters except axial length between Group S and Group L, Groups S1 and L1, or Groups S2 and L2 (p > 0.05). CONCLUSIONS: The anterior parameters of patients with high myopia did not change with the axial length.

ERRα expression in ovarian cancer and promotes ovarian cancer cells migration in vitro.

PURPOSE: Ovarian cancer is the leading cause of death from a gynaecological malignancy in the developed world, and is characterized by invasion and metastasis and thus causes a high fatality rate. Estrogen-related receptor alpha (ERRα) has been demonstrated to play a widespread and pathophysiological relevant role in tumourigenesis and development. The aim of this study was to investigate the effect of ERRα expression on the progression of ovarian cancer. METHODS: The correlation between ERRα expression level and clinical pathological parameters in ovarian cancer tissues were analysed via cancer public database CPTAC. The expression level of ERRα in ovarian cancer cells were confirmed by RT-qPCR and Western blot methods. The cellular ERRα expression was up-regulated by lentivirus transfection and down-regulated by specific antagonist. The invasion and metastasis capabilities of ovarian cancer cells were characterized by wound healing assay and trans-well chamber assay. RESULTS: The CPTAC database showed that the ERRα expression levels were higher in the late-stage and high-grade ovarian cancer tissues than in early-stage and low-grade tissues. Ovarian cancer cells with higher-expression ERRα exhibited stronger invasion and metastasis capabilities in vitro. After up-regulating the ERRα expression level, the invasion and metastasis capabilities of ovarian cancer cells were enhanced, while down-regulation weakened. Moreover, the wound sealing rate was positively correlated with the expression of ERRα mRNA expression level (r = 0.921, P < 0.01), and the cell invasiveness was also positively correlated with the cellular ERRα mRNA expression level (r = 0.926, P < 0.01). CONCLUSIONS: Our results suggest that ERRα may promote the progression of ovarian cancer, and may serve as a promising predictive biomarker.

Genetic diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum on Bioko Island, Equatorial Guinea and global comparative analysis.

BACKGROUND: Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. METHODS: 153 blood spot samples from Bioko malaria patients were collected during 2016-2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. RESULTS: A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN-dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. CONCLUSIONS: Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.

Extracellular vesicles from Fasciola gigantica induce cellular response to stress of host cells.

Extracellular vesicles (EVs) from parasitic helminths play an important role in immunomodulation. However, EVs are little studied in the important parasite Fasciola gigantica. Here the ability of EVs from F. gigantica to induce cellular response to stress (reactive oxygen species generation, autophage and DNA damage response) in human intrahepatic biliary epithelial cells (HIBEC) was investigated. F. gigantica-derived EVs were isolated by ultracentrifugation, and identified with transmission electron microscopy, nanoparticle size analysis and parasite-derived EV markers. Internalization of EVs by HIBEC was determined by confocal immunofluorescence microscopy and flow cytometry. ROS levels in HIBEC were detected by molecular probing. EVs-induced autophagy and DNA-damaging effects were determined by evaluating expression levels of light chain 3B protein (LC3B), phosphor- H2A.X and phosphor-Chk1, respectively. Results revealed that EVs with sizes predominately ranging from 39 to 110 nm in diameter were abundant in adult F. gigantica and contained the parasite-derived marker proteins enolase and 14-3-3, and EVs were internalized by HIBEC. Further, uptake of EVs into HIBEC was associated with increased levels of reactive oxygen species, LC3Ⅱ, phosphor-H2A.X and phosphor-Chk1, suggesting EVs are likely to induce autophagy and DNA damage & repair processes. These results indicate F. gigantica EVs are associated with modulations of host cell responses and have a potential important role in the host-parasite interactions.

Optimization of Extraction and Purification of Polysaccharides from Veronicastrum axillare, and Evaluation of Their Biological Activities.

Veronicastrum axillare polysaccharides (VAP) were isolated by cellulase-assisted digestion. The optimum conditions (2 % cellulase, 47 °C for 2.5 h, then, 95 °C for 2.5 h, pH 4.1, solid/liquid ratio 1 : 7.6) were identified by a combination of single factor optimization and response surface DOE (design of experiment) methods, and achieved a yield of 4.7 %. Treatment with 1 % TCA for 10 min, then, 2 % DEAE-cellulose removed protein and colored impurities. Purified VAP retained most of the radical-scavenging activities and GES-1 cell protection capability in vitro, indicating VAP were the key active components of V. axillare. Some molecular features were identified by FT-IR and NMR analyses. The molecular weight was estimated from DOSY NMR experiments to be around 21 kDa. There were 6.3 % uronic acid residues in the VAP. The constituent sugars after TFA hydrolysis were identified by HPLC to include glucose, arabinose, rhamnose, galactose, and xylose in a molar ratio of 405 : 259 : 82 : 42 : 1.

Newly excysted juveniles (NEJs) of Fasciola gigantica induce mice liver fibrosis and M2 macrophage-like phenotype in vivo.

Liver flukes of animals are parasitic flatworms of major socioeconomic importance in many countries. Particularly, Fasciola gigantica is a leading cause of production losses to the livestock (mainly sheep and cattle) and meat industries due to clinical disease, reduced weight gain and milk production, and deaths. Immune responses induced by helminth have been extensively studied, but there is limited information on this aspect by F. gigantica, especially on macrophages induced with this parasite. Studies have shown that host immune responses induced by parasitic infection is greatly correlated with the macrophage polarization axis. In the present study, we used the murine model of F. gigantica to explore the interaction of host and F. gigantica. We found F. gigantica NEJs promoted pathology and fibrosis of mice liver, and the enlargement of mice spleen. We also showed that macrophages were recruited to mice peritoneal cavity at 5 days post infection. By evaluating the expression of genetic markers of M2 macrophages such as Arg-1, Ym1 and RELMɑ, and genetic marker of M1 macrophages iNOS, we showed that M2 macrophages were induced by F. gigantica. M2 macrophages are central to the immune response during helminth infection, and our findings in this study provided insight into the immune interaction between F. gigantica and host.

Newly excysted juveniles of Fasciola gigantica trigger the release of water buffalo neutrophil extracellular traps in vitro.

Polymorphonuclear neutrophils (PMNs) are the most abundant leukocytes and are among the first line of immune system defense. PMNs can form neutrophil extracellular traps (NETs) in response to some pathogens. The release of NETs plays an important role in trapping and killing invading parasites. However, the effects of NETs on parasitic trematode infections remain unclear. In the present study, water buffalo NET formation, triggered by the newly excysted juveniles (NEJs) of Fasciola gigantica, was visualized by scanning electron microscopy. The major components of the structure of NETs were characterized by immunofluorescence. Viability of flukes incubated with water buffalo PMNs were examined under light microscopy. The results revealed that F. gigantic juveniles triggered PMN-mediated NETs. These NETs were confirmed to comprise the classic characteristics of NETs: DNA, histones, myeloperoxidase and neutrophil elastase. Although NETs were formed in response to viable larvae, the larvae were not killed in vitro. These results suggest that NET formation may serve as a mechanism to hamper the migration of large larvae to facilitate immune cells to kill them. This study demonstrates, for the first time, that parasitic trematode juveniles can trigger NET formation.

Nasogastric tube decompression is unnecessary in patients undergoing laparoscopic nephroureterectomy for localized upper tract urothelial carcinoma.

BACKGROUND/PURPOSE: This study investigates the safety and feasibility to perform laparoscopic nephroureterectomy (LNU) for upper tract urothelial carcinoma (UTUC) without routine nasogastric tube (NGT) decompression. METHODS: The hospital-based samples comprised of 100 consecutive UTUC patients receiving elective LNU performed by two experienced surgeons. The nationwide data was based on LHID2005 composed of one million beneficiaries randomly selected from the Taiwan National Health Insurance Research Database to identify patients with the diagnoses of UTUCs receiving LNUs. We then compared baseline characteristics, peri-operative data, convalescence parameters and complications between two groups stratified by use of NGT tube. RESULTS: The hospital-based samples composed of 50 subjects with NGT and 50 without. There were no significant differences in baseline characteristics between two groups. Peri-operative and convalescence parameters were similar when comparing no NGT versus NGT: blood loss of 206 vs. 165 mL; operative time of 180.5 vs.181.1 min; days to intake was 2.1 vs.1.7 days; and hospital stay of 7.8 vs. 7.5 days (all p > 0.05). The nationwide study samples comprised 140 subjects, of which 72 were with NGT and 68 were with no NGT. The baseline data, complications and length of hospital stay were similar between two groups. CONCLUSION: Surgery-naïve patients with localized UTUC received LNU without peri-operative NGT is safe and feasible.

Phylogenetic, comparative genomic and structural analyses of human Streptococcus agalactiae ST485 in China.

BACKGROUND: Streptococcus agalactiae (Group B Streptococcus, GBS) is a common bacteria species infecting both human and bovine. Previous studies have shown that the GBS isolated from human and bovine are mostly unrelated and belong to separate populations. However, recently, the bovine GBS CC103 has become the dominant epidemic strain and frequently isolated from human patients. In particular, the ST485 GBS, a member of CC103, has become the new dominant ST in China and exhibited very high pathogenicity. This phenomenon is not consistent with the established understanding about the relationship between bovine and human GBS, which needs to be re-investigated. RESULTS: The genome-based phylogenetic analysis showed that the human and bovine GBS CC103 strains had very close genetic relationship and they were alternately distributed on the evolutionary tree. CC103 strains evolved into several branches, including the ST485, which exhibited high pathogenicity and specifically infected human. Compared to other CC103 strains, the ST485 lacked Lac.2 gene structure and acquired the CadDX gene structure in their genomes. CONCLUSIONS: Our results indicate that GBS CC103 could propagate across human and bovine, and GBS ST485 might evolve from the ST103 that could infect both human and bovine. Moreover, the recombination of Lac.2 and CadDX gene structures might play an important role in the formation of highly pathogenic ST485 in China.

Paracrine Factors Secreted by MSCs Promote Astrocyte Survival Associated With GFAP Downregulation After Ischemic Stroke via p38 MAPK and JNK.

Astrocytes are critical for ischemic stroke, and understanding their role in mesenchymal stem cell (MSC)-mediated protection against ischemic injury is important. The paracrine capacity of MSCs has been proposed as the principal mechanism contributing to the protection and repair of brain tissue. In the present study, an in vitro oxygen-glucose deprivation (OGD) model was used to mimic ischemic injury. OGD-induced astrocytes were reperfused with MSC-conditioned medium (MSC-CM) or co-cultured with MSCs for 24 h to create an environment abundant in paracrine factors. The results indicated that both situations could protect astrocytes from apoptosis, increase cell metabolic activity, and reduce glial fibrillary acidic protein (GFAP) overexpression; however, the effects of co-culturing with MSCs were more positive. Paracrine factors suppressed the activation of p38 MAPK, JNK, and their downstream targets p53 and STAT1. Inhibition of p38 MAPK, JNK, p53, and STAT1 attenuated astrocyte injury and/or GFAP upregulation. Activation of p38 MAPK and JNK suppressed the beneficial effects of paracrine factors, resulting in decreased survival and GFAP overexpression. These results suggest that paracrine factors inhibit p38 MAPK and JNK, and most likely by regulating their downstream targets, p53 and STAT1, to promote astrocyte survival associated with GFAP downregulation after ischemic stroke in vitro.

Zoonotic helminths parasites in the digestive tract of feral dogs and cats in Guangxi, China.

BACKGROUND: In Guangxi, a province of southern China, an important number of dogs and cats roam freely in rural settings, and the presence of these animals in proximity of people may represent a risk of parasitic zoonoses. The objective of the present study was to investigate the presence and identify gastrointestinal helminths in feral carnivores in Guangxi province. Therefore, post mortem examination was performed in 40 dogs and in 39 cats. RESULTS: The Gastrointestinal helminths were found in all the necropsied dogs and in 37 out of 39 cats. Fifteen species were identified including 7 trematodes, 3 cestodes and 5 nematodes. Most of them may be responsible for zoonotic infections. CONCLUSIONS: Major zoonotic gastrointestinal helminths, including liver and intestinal flukes, Toxocara spp., and Ancylostoma spp., are present in feral dogs and cats in Guangxi, and may represent a significant risk for public health.