Virome diversity shaped by genetic evolution and ecological landscape of Haemaphysalis longicornis.

BACKGROUND: Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. RESULTS: We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. CONCLUSIONS: These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.

Effect of interval between oocyte retrieval and resuscitation embryo transfer on pregnancy outcomes.

Objectives: Resuscitation transfer of embryos after elective cryopreservation has been widely applied in in vitro fertilization-embryo transfer (IVF-ET) therapy for human infertility or sterility owing to higher embryo implantation rates. This method separates oocyte retrieval from embryo transfer. The optimal time for frozen embryo transfer (FET) remains unknown. Therefore, this study mainly compares the advantages and disadvantages of delayed FET and immediate FET through retrospective analysis. Methods: We analyzed real world data of patients who underwent resuscitation transplantation between October 2019 and July 2021 at the Reproductive Center of Chengdu Jinjiang Hospital for Women's and Children's Health. Propensity score matching was applied to control potential confounding factors. A total of 5,549 patients who received at least one FET were analyzed. Patients undergoing transplantation within 60 days of oocyte retrieval were included in the immediate FET group (n = 1,265) and those undergoing transplantation > 60 days after retrieval were included in the delayed FET group (n = 4,284). Results: Live birth rates between the two groups were comparable (45.25% vs. 45.76%, p = 0.757). Moreover, no difference was observed in the rates of biochemical pregnancy (64.50% vs. 66.80%), clinical pregnancy (55.24% vs. 56.83%), ectopic pregnancy (1.47% vs. 1.39%), early miscarriage (14.41% vs. 16.20%), late miscarriage (2.21% vs. 2.09%), singleton premature delivery (16.67% vs. 18.29%), and neonatal deformity (1.97% vs. 1.80%). After stratifying the patients based on the type of embryo transferred, number of embryos transferred, FET protocol, and good prognosis criteria, live birth rates remained comparable between the two groups (p > 0.05). Conclusion: Pregnancy outcomes were comparable between the immediate and delayed FET groups.

The Predictive Value of Red Cell Distribution Width and Red Cell Distribution Width to Erythrocyte Count Ratio for Adverse Cardiovascular Events During the Hospitalization of Patients of ST-segment Elevation Myocardial Infarction.

BACKGROUND: High red cell distribution width (RDW) is correlated with poor prognosis in acute coronary syndromes (ACS), including ST-segment elevation myocardial infarction (STEMI). However, the association of red cell distribution width to erythrocyte count ratio (RER) with STEMI undergoing percutaneous coronary intervention (PCI) during hospitalization has not been investigated. Therefore, we performed a retrospective study to investigate whether RER is associated with STEMI patients after PCI during hospitalization. METHODS: A total of 331 patients, who were hospitalized for STEMI and underwent PCI, were enrolled. Receiver operating characteristic curve (ROC) analyses were used to find the cutoff value of RER and classify the patients into two groups including higher RER group and lower RER group by cutoff value. Differences between measured parameters in higher RER and lower RER groups were analyzed by the Mann-Whitney U test. The evaluation correlation of RDW, red blood cell, and RER with major adverse cardiovascular events was determined by bivariate regression analysis. Univariate logistic regression analysis was used to determine the factors associated with adverse cardiovascular events during the hospitalization of STEMI patients. Multivariate logistic regression analysis was performed to evaluate the potential independent predictors of STEMI. RESULTS: According to ROC analysis, the cutoff value of RER and RDW is 3.10 and 13.9, the sensitivity is 51% and 35%, the specificity is 76% and 80%, respectively. RER showed improved diagnostic capacity compared to RDW in correlation with adverse cardiovascular events during hospitalization in STEMI patients (p < 0.001). Compared with the lower RER group, the incidence of adverse cardiovascular events in STEMI patients is elevated in the higher RER group (75% vs. 64.5%, p < 0.05). Bivariate regression analysis indicated that RER and RDW showed a good correlation with adverse cardiovascular events, and the difference was statistically significant (R = 0.10 p < 0.05 vs. R = 0.05 p < 0.05). Univariate logistic regression analysis showed that age, heart rate, left ventricular ejection fraction, hyperlipidemia, RDW, mean platelet volume, total cholesterol, and RER were correlated with the occurrence of adverse cardiovascular events during the hospitalization of STEMI patients (p < 0.05). Multivariate logistic regression analysis demonstrated that RER could be an independent predictor of adverse cardiovascular events in STEMI patients (B: 0.574, OR: 1.776, 95% CI: 1.043 ~ 3.023, p < 0.05). CONCLUSIONS: RER and RDW demonstrated good correlation with adverse cardiovascular events during hospitalization in STEMI patients. RER is a potential independent predictor of adverse cardiovascular events during hospitalization in STEMI patients.

α-Catenin is an inhibitor of transcription.

α-Catenin (α-cat) is an actin-binding protein required for cell-cell cohesion. Although this adhesive function for α-cat is well appreciated, cells contain a substantial amount of nonjunctional α-cat that may be used for other functions. We show that α-cat is a nuclear protein that can interact with ß-catenin (ß-cat) and T-cell factor (TCF) and that the nuclear accumulation of α-cat depends on ß-cat. Using overexpression, knockdown, and chromatin immunoprecipitation approaches, we show that α-cat attenuates Wnt/ß-cat-responsive genes in a manner that is downstream of ß-cat/TCF loading on promoters. Both ß-cat- and actin-binding domains of α-cat are required to inhibit Wnt signaling. A nuclear-targeted form of α-cat induces the formation of nuclear filamentous actin, whereas cells lacking α-cat show altered nuclear actin properties. Formation of nuclear actin filaments correlates with reduced RNA synthesis and altered chromatin organization. Conversely, nuclear extracts made from cells lacking α-cat show enhanced general transcription in vitro, an activity that can be partially rescued by restoring the C-terminal actin-binding region of α-cat. These data demonstrate that α-cat may limit gene expression by affecting nuclear actin organization.

Tumor stiffness is unrelated to myosin light chain phosphorylation in cancer cells.

Many tumors are stiffer than their surrounding tissue. This increase in stiffness has been attributed, in part, to a Rho-dependent elevation of myosin II light chain phosphorylation. To characterize this mechanism further, we studied myosin light chain kinase (MLCK), the main enzyme that phosphorylates myosin II light chains. We anticipated that increases in MLCK expression and activity would contribute to the increased stiffness of cancer cells. However, we find that MLCK mRNA and protein levels are substantially less in cancer cells and tissues than in normal cells. Consistent with this observation, cancer cells contract 3D collagen matrices much more slowly than normal cells. Interestingly, inhibiting MLCK or Rho kinase did not affect the 3D gel contractions while blebbistatin partially and cytochalasin D maximally inhibited contractions. Live cell imaging of cells in collagen gels showed that cytochalasin D inhibited filopodia-like projections that formed between cells while a MLCK inhibitor had no effect on these projections. These data suggest that myosin II phosphorylation is dispensable in regulating the mechanical properties of tumors.

[The clinical and experimental analyses of a multiple myeloma patient with derivative der(Y;1)].

OBJECTIVE: To investigate the clinical significance of a rare chromosome abnormality der(Y)t(Y;1) in a patient with multiple myeloma (MM). METHODS: The chromosome spread was prepared after 24 h culture of bone marrow. G-banding technique was used to analyze the karyotype. Fluorescence in situ hybridization (FISH) was performed to ascertain the origin of abnormal chromosome detected by conventional karyotypic analysis. Flow cytometry was used to detect the expression of the CD38/CD138/ZAP70. Immunoelectrophore was applied to identify the type of immunoglobulin. RESULTS: A complex pattern of chromosome rearrangement was observed: 92,XXYY[3]/49,X,der(Y)t(Y;1)(q12;q21),t(11;14)(q13;q32),+18,+20,+21[47]/49,X,idem,del(13q22),ace[1]/98,XX,der(Y)t(Y;1) x 2,+18,+18,+20,+20,+21,+21[10]/46,XY[19]. The result was confirmed by metaphase-FISH. The type of immunoglobulin was IgD with the level of 6.24g/L. The CD38/CD138 was positive but ZAP70 was negative. CONCLUSION: Structural abnormality of chromosome Y is rare in blood malignancy. Most of them were described in myelodysplastic syndrome or myeloproliferative disorders. It is the first report of der(Y)t(Y;1) abnormality in multiple myeloma.

Engineering glutathione transferase to a novel glutathione peroxidase mimic with high catalytic efficiency. Incorporation of selenocysteine into a glutathione-binding scaffold using an auxotrophic expression system.

Glutathione peroxidase (GPx, EC 1.11.1.9) protects cells against oxidative damage by catalyzing the reduction of hydroperoxides with glutathione (GSH). Several attempts have been made to imitate its function for mechanical study and for its pharmacological development as an antioxidant. By replacing the active site serine 9 with a cysteine and then substituting it with selenocysteine in a cysteine auxotrophic system, catalytically essential residue selenocysteine was bioincorporated into GSH-specific binding scaffold, and thus, glutathione S-transferase (GST, EC 2.5.1.18) from Lucilia cuprina was converted into a selenium-containing enzyme, seleno-LuGST1-1, by genetic engineering. Taking advantage of the important structure similarities between seleno-LuGST1-1 and naturally occurring GPx in the specific GSH binding sites and the geometric conformation for the active selenocysteine in their common GSH binding domain-adopted thioredoxin fold, the as-generated selenoenzyme displayed a significantly high efficiency for catalyzing the reduction of hydrogen peroxide by glutathione, being comparable with those of natural GPxs. The catalytic behaviors of this engineered selenoenzyme were found to be similar to those of naturally occurring GPx. It exhibited pH and temperature-dependent catalytic activity and a typical ping-pong kinetic mechanism. Engineering GST into an efficient GPx-like biocatalyst provided new proof for the previous assumption that both GPx and GST were evolved from a common thioredoxin-like ancestor to accommodate different functions throughout evolution.