Doxorubicin resistance in breast cancer is mediated via the activation of FABP5/PPARγ and CaMKII signaling pathway.

Breast cancer is the most prevalent malignancy among women. Doxorubicin (Dox) resistance was one of the major obstacles to improving the clinical outcome of breast cancer patients. The purpose of this study was to investigate the relationship between the FABP signaling pathway and Dox resistance in breast cancer. The resistance property of MCF-7/ADR cells was evaluated employing CCK-8, Western blot (WB), and confocal microscopy techniques. The glycolipid metabolic properties of MCF-7 and MCF-7/ADR cells were identified using transmission electron microscopy, PAS, and Oil Red O staining. FABP5 and CaMKII expression levels were assessed through GEO and WB approaches. The intracellular calcium level was determined by flow cytometry. Clinical breast cancer patient's tumor tissues were evaluated by immunohistochemistry to determine FABP5 and p-CaMKII protein expression. In the presence or absence of FABP5 siRNA or the FABP5-specific inhibitor SBFI-26, Dox resistance was investigated utilizing CCK-8, WB, and colony formation methods, and intracellular calcium level was examined. The binding ability of Dox was explored by molecular docking analysis. The results indicated that the MCF-7/ADR cells we employed were Dox-resistant MCF-7 cells. FABP5 expression was considerably elevated in MCF-7/ADR cells compared to parent MCF-7 cells. FABP5 and p-CaMKII expression were increased in resistant patients than in sensitive individuals. Inhibition of the protein expression of FABP5 by siRNA or inhibitor increased Dox sensitivity in MCF-7/ADR cells and lowered intracellular calcium, PPARγ, and autophagy. Molecular docking results showed that FABP5 binds more powerfully to Dox than the known drug resistance-associated protein P-GP. In summary, the PPARγ and CaMKII axis mediated by FABP5 plays a crucial role in breast cancer chemoresistance. FABP5 is a potentially targetable protein and therapeutic biomarker for the treatment of Dox resistance in breast cancer.

Molecular prevalence of Tetratrichomonas gallinarum and Trichomonas gallinae in three domestic free-range poultry breeds in Anhui Province, China.

Tetratrichomonas gallinarum and Trichomonas gallinae can colonize the alimentary tract of domestic birds. However, little information is available on the epidemiology of the two trichomonad species in domestic free-range poultry in China. In this study, the occurrence and genetic characteristic of T. gallinarum and T. gallinae among free-range chickens, ducks, and geese in Anhui Province, China, were investigated. The 1910 fecal samples collected from 18 free-range poultry farms throughout Anhui Province were examined for the presence of T. gallinarum and T. gallinae by PCR and sequence analysis of the small subunit (SSU) rRNA gene of T. gallinarum and ITS1-5.8S-ITS2 sequence of T. gallinae. The overall occurrence of T. gallinarum in poultry was 1.2% (22/1910), with infection rates of 2.1% (17/829) in chickens, 0.2% (1/487) in ducks, and 0.7% (4/594) in geese. The constructed phylogeny tree using the concatenated ITS1-5.8S-ITS2 region and SSU rRNA indicated the T. gallinarum isolates detected in this study were closely related to previously defined genogroups A, D, and E, respectively. Nine (0.5%) fecal samples were positive for T. gallinae, with infection rates of 0.8% (7/829) in chickens, 0.4% (2/487) in ducks, and 0% (0/594) in geese. Sequence and phylogenetic analysis showed that four T. gallinae ITS1-5.8S-ITS2 sequences obtained from chicken feces and one duck fecal sample belonged to genotype ITS-OBT-Tg-1. This is the first report of the prevalence and genetic characterization of T. gallinarum and T. gallinae in free-range chickens, ducks, and geese in China.

[Retrospective Analysis of Hematological Phenotypes in Patients with Gene Mutation and Deletion α-Thalassemia].

OBJECTIVE: To explore the differences between hematological phenotypes of patients with different genotypes in gene mutations and deletion α- thalassemia. METHODS: By screening the α- thalassemia gene test results in the First Affiliated Hospital, Sun Yat-Sen University from January 2015 to April 2020, the patients with mutation and deletion α- thalassemia were obtained, then the differences between hematological phenotypes of patients with different genotypes were analyzed. RESULTS: There were 96 patients with mutation combined with deletion α- thalassemia from the results of 24 054 α- thalassemia patients screened out, including 79 patients with non-deletion Hb H disease (αTα/--SEA) and 17 patients with mild α- thalassemia (αTα/-α), the incidence was 0.42%. Except the number of red blood cells (RBC) and mean corpuscular volume (MCV), the hemoglobin (Hb) concentration, hematocrit (Ht), average red blood cell hemoglobin concentration (MCHC), average red blood cell hemoglobin amount (MCH), average red blood cell volume (MCV) of the patients with αTα/--SEA genotype were significantly lower than those with αTα/-α genotype. The Hb of the patients with αCSα/--SEA and αQSα/--SEA genotype was (86±20)g/L and (84±9)g/L, respectirely, which was significantly lower than (114±16) g/L of αWSα/--SEA genotype (P<0.05); The MCHC of patients with αCSα/--SEA and αQSα/--SEA genotype was (278.8±8.5) g/L and (282.1±21.1)g/L, respectirely, which was also significantly lower than (315.4±19.5) g/L of αWSα/--SEA genotype (P<0.05); There was no significant difference between the patients with αCSα/--SEA and αQSα/--SEA genotype in hematological phenotypes. Except MCH and MCV, there was no significant differences between the patients with αWSα/--SEA and αTα/-α genotype in RBC, Hb, and Ht. The result of Hb A2 was (2.3±0.9)% for only 27 patients who performed electrophoretic analysis. There was no significant difference between the patients with αTα/--SEA and αTα/-α genotype in Hb A2, aslo among 3 types of the patients with αTα/--SEA genotype. CONCLUSION: The hematological phenotype changes caused by αWSα/--SEA genotype are similar to those of mild α- thalassemia, and both of them are significantly lighter than those patients with αCSα/--SEA and αQSα/--SEA genotype.

Molecular prevalence and characterization of Cryptosporidium in domestic free-range poultry in Anhui Province, China.

Free-range chickens might mediate the spread of Cryptosporidium oocysts to humans and other animals. Few studies have evaluated the prevalence of Cryptosporidium species in domestic free-range poultry in China. Here, we characterized the prevalence and distribution of species and genotypes of Cryptosporidium in domestic free-range chickens, ducks, and geese in Anhui Province, China. A total of 1910 fresh fecal samples from three poultry species were examined from 18 free-range poultry farms by nested PCR and analysis of the Cryptosporidium SSU rRNA gene. The overall prevalence of Cryptosporidium species was 2.9% (55/1910), with infection rates of 1.3% (11/829) in chickens, 7.3% (36/487) in ducks, and 1.4% (8/594) in geese. C. baileyi (0.6%), C. meleagridis (0.2%), C. galli (0.2%), and C. xiaoi-like genotype (0.2%) were identified in chickens, and only C. baileyi was identified in ducks and geese, with infection rates of 7.4% and 1.3%, respectively. C. baileyi was the most prevalent species. Sequencing of the GP60 gene revealed that the C. meleagridis isolates belonged to the IIIbA26G1R1b subtype. This is the first study to document C. galli and C. xiaoi-like genotype in domestic free-range chickens in China. These findings expand the range of avian hosts known for Cryptosporidium and highlight the need for additional studies to characterize the diversity of Cryptosporidium in avian species.

A long-wavelength fluorescent probe with a large Stokes shift for lysosome-targeted imaging of Cys and GSH.

Biothiols including cysteine (Cys) and glutathione (GSH) are biological signaling molecules responsible for cell detoxification, cell metabolism and neutralization of reactive oxygen species. Here, we synthesized a long-wavelength fluorescent probe, DCIMA, for lysosome-targeted imaging of Cys and GSH in living cells. DCIMA is consisted of a dicyanoisophorone core modified with an acrylate group for biothiol detection through the Michael addition reaction and a morpholine group as the lysosome-targeting agent. The presence of the electron-donating morpholine group also enhances the intramolecular charge transfer mechanism of the probe, thereby enabling its long-wavelength fluorescence emission (670 nm) and large Stokes shift (180 nm). In concentration range of 0-30 µM, the probe was determined to react quickly with both Cys and GSH with low detection limits (<5 min, 35.2 nM for GSH and 34.8 nM for Cys) and achieve the sensitive fluorescence imaging of the biothiols located in the lysosomes of living cells.

The first report of Cryptosporidium testudinis in Chinese alligators (Alligator sinensis) in China.

Several Cryptosporidium species that infect reptiles, especially squamates, are well described, but there is limited data about Cryptosporidium species infecting crocodilians. In this study, we assess the occurrence of intestinal parasites using traditional microscopic examination and describe the prevalence and Cryptosporidium species in the captive-bred Chinese alligators (Alligator sinensis) in eastern China using molecular methods. The results of microscopic examination showed that no intestinal parasites were detected among the 491 fecal samples examined from the Chinese alligators. The overall prevalence for Cryptosporidium was 0.41% (2/491) by PCR detection using the SSU rRNA locus. Sequence and phylogenetic analysis of the SSU rRNA, COWP, and actin genes revealed the presence of Cryptosporidium testudinis, which has been isolated primarily from chelonians. This is the first detection of the specific DNA of C. testudinis in the feces of the Chinese alligator. This study expands our knowledge of the Cryptosporidium species involved in crocodiles, and more extensive studies are necessary to confirm the validity of C. testudinis in crocodiles.

Prevalence of Tetratrichomonas buttreyi and Pentatrichomonas hominis in yellow cattle, dairy cattle, and water buffalo in China.

The trichomonad species Tetratrichomonas buttreyi and Pentatrichomonas hominis have been reported in the bovine digestive tract in only a few studies, and the prevalence and pathogenicity of these two protists in cattle herds remain unknown. In this study, the prevalence of T. buttreyi and P. hominis in yellow cattle, dairy cattle, and water buffalo in Anhui Province, China, was determined with a PCR analysis of the small subunit ribosomal RNA genes. The overall infection rates for T. buttreyi and P. hominis were 8.1% and 5.4%, respectively. Double infections were found in 15 (1.6%) samples from four farms. The prevalence of P. hominis in cattle with abnormal feces was significantly higher than that in cattle with normal feces (χ2 = 13.0, p < 0.01), and the prevalence of T. buttreyi in the northern region of Anhui Province was also significantly higher than that in the mid region (χ2 = 16.6, p < 0.01). Minor allelic variations were detected in the T. buttreyi isolates from cattle in this study, as in other hosts in previous studies. Morphological observations, together with the PCR analysis, demonstrated that the trichomonads isolated in this study were P. hominis. The presence of T. buttreyi and P. hominis indicated that cattle are natural hosts of these two trichomonads and could be a potential source of P. hominis infections in humans and other animal hosts.

[Gaseous Emission Characterization of Civil Aviation Aircraft During Takeoff].

During takeoff, high engine thrust and large fuel consumption are required to produce enough power for aircraft lift-off which has more impacts on human health and environment than the other activities. Boeing 737-800 was selected as a typical type in the study. Based on simulation of aircraft performance, air pollution emissions were accurately calculated for different takeoff processes. According to the results, NOx was the most abundant emission during takeoff. Emissions of NOx, CO, HC, and SO2 during takeoff with normal method were 4.849, 0.062, 0.031, 0.229 kg respectively. The assumed temperature method could be used to reduce thrust by setting an assumed temperature which was greater than actual temperature. This method resulted in decreased NOx emission and increased CO emission. And emissions of HC and SO2 had no significant changes. Compared with these results, the emissions calculated by ICAO emission model led to relatively large errors. And the emission level of normal takeoff method was approximately equal to the emission level of small cars traveling 9508 km. The modified model provides the basis for the accurate estimation of the air pollution emission inventory of airport.