Huberfischer9085

Iron is an essential nutrient in bacteria. Its ferrous form, mostly present in low oxygen and acidic pH environments, can be imported using the specific Ftr-type transport system, which encompasses the conserved FtrABCD system found in pathogenic bacteria such as Bordetella, Brucella and Burkholderia. The nonpathogenicity and versatile metabolism of Rubrivivax gelatinosus make it an ideal model to study the FtrABCD system. Here, we report a new aspect of its regulation and the role of the periplasmic proteins FtrA and FtrB using in vivo and in vitro approaches. We investigated the metal binding mode and redox state of copper and iron to FtrA by crystallography and biophysical methods. An 'as isolated' FtrA protein from the bacterial periplasm contained a copper ion (Cu+ ) identified by electron paramagnetic resonance (EPR). Copper is coordinated by four conserved side chains (His and Met) in the primary metal site. Structural analysis of R. gelatinosus FtrA and FtrA homologues revealed that copper binding induces a rearrangement of the His95 imidazole ring, releasing thereafter space, as well as both Asp45 and Asp92 side chains, for iron binding in the secondary metal site. EPR highlighted that FtrA can oxidize the bound ferrous ion into the ferric form by reducing the bound Cu2+ into Cu+ , both metal sites being separated by 7 Å. Finally, we showed that FtrB binds iron and not copper. These results provide new insights into the mechanism of ferrous iron utilization by the conserved FtrABCD iron transporter for which we propose a new functional model.

To develop a convenient method for rapid purification of fresh Pheretima proteins and assess the inhibitory effect of these proteins against pulmonary fibrosis.

The crude extract of fresh Pheretima was obtained by freeze-drying method and then purified by size exclusion chromatography. The composition of the purified proteins was analyzed by mass spectrometry. MRC-5 cells were treated with 5 ng/mL TGF-β1 alone (model group) or in combination with SB431542 (2 μmol/L) or the purified proteins (13.125 μg/mL), and the cytotoxicity of purified proteins and their inhibitory effects on cell proliferation were detected with CCK8 assay. Flow cytometry was used to detect the changes in cell apoptosis, and the cellular expressions of

-SMA, Vimentin, E-cadherin, collagen I, Smad2/3 and P-Smad2/3 were detected using RT-PCR and Western blotting. In the animal experiment, adult male C57BL/6 mice were subjected to intratracheal instillation of bleomycin followed by treatment with the purified proteins (5 mg/mL) for 21 raphy can inhibit pulmonary fibrosis in mice by regulating the TGF-β/ Smad pathway.

To investigate the expression of Talin1 in the fallopian tube and chorionic villi in patients with tubal pregnancy and its role in regulating invasion and migration of trophoblasts.

Immunohistochemistry and Western blotting were used to detect the localization and expression level of Talin1 in the fallopian tube and chorionic villi in patients with tubal pregnancy and in women with normal pregnancy. In the cell experiment, HTR-8/SVneo cells was transfected with Talin1 siRNA and the changes in cell invasion and migration were assessed using scratch assay and Transwell assay. The expressions of MMP-2, MMP-9, N-cadherin and Snail in the transfected cells were detected by qRT-PCR and Western blotting.

Positive expression of Talin1 was detected in both normal fallopian tube tissues and tissues from women tubal pregnancy, and its expression was localized mainly in the cytoplasm of cilia cells. The expression level of Talin1 was significantly higher in both the fallopian tube and chorionic villi in women with tubal pregnancy than in normal fallopian tube and chorionic villi samples (

< 0.01). In HTR-8/SVneo cells, transfection with Talin1 siRNA significantly inhibited cell invasion (

< 0.01) and migration (

< 0.05), down-regulated the expression of N-cadherin, MMP-2 and Snail (

< 0.05), and up-regulated the expression of MMP-9 in the cells (

< 0.05).

The expression of Talin1 in the fallopian tube and chorionic villi is significantly increased in women with tubal pregnancy, suggesting the association of Talin1-regulated trophoblast cell invasion with the occurrence of tubal pregnancy.

The expression of Talin1 in the fallopian tube and chorionic villi is significantly increased in women with tubal pregnancy, suggesting the association of Talin1-regulated trophoblast cell invasion with the occurrence of tubal pregnancy.

To investigate the clinical characteristics of lower extremity arterial disease (LEAD) and its risk factors in patients with diabetic foot ulcer (DFU).

We retrospectively collected the clinical and follow-up data of 650 patients with DFU treated in the Department of Endocrinology and Metabolism of Nanfang Hospital between January, 2017 and December, 2019. Lorlatinib order We compared the data between patients who had LEAD and those without LEAD and used a multivariate logistic regression model to analyze the risk factors of LEAD in DFU patients.

Among the 650 DFU patients, 470 (72.4%) had LEAD. The patients were followed up for a mean of 3.5 months, and the mean healing time of DFU was 2.55 months; healing of DFU occurred in 453 patients and 183 patients received amputation. The patients with LEAD and those without LEAD differed significantly in age, hospitalization costs, diastolic blood pressure (DBP), glycated hemoglobin, blood lipid levels, disease course, ankle brachial index, healing time, smoking history, clinical outcomes, Wagner grade and imaging results (

< 0.05). Multivariate logistic regression analysis identified age (OR=1.070, 95%

1.049-1.091), smoking history (OR= 2.013, 95%

1.268-3.195), and a decreased DBP (OR=0.980, 95%

0.963-0.997) as independent risk factors for LEAD in DFU patients. A prolonged healing time was a prominent clinical feature of DFU complicated by LEAD.

DFU patients have a high incidence of LEAD, which leads to high rates of disability and mortality and is associated with an advanced age, high smoking rate and longer healing time. A decreased DBP is also a risk factor for LEAD in DFU patients.

DFU patients have a high incidence of LEAD, which leads to high rates of disability and mortality and is associated with an advanced age, high smoking rate and longer healing time. A decreased DBP is also a risk factor for LEAD in DFU patients.

To investigate the inhibitory effect of AZD2014, a dual mTORC1/2 inhibitor, against acute graft rejection in a rat model of allogeneic liver transplantation.

Liver transplantation from Lewis rat to recipient BN rat (a donor-recipient combination that was prone to induce acute graft rejection) was performed using Kamada's two-cuff technique. The recipient BN rats were randomized into 2 groups for treatment with daily intraperitoneal injection of AZD2014 (5 mg/kg,

=4) or vehicle (2.5 mL/kg,

=4) for 14 consecutive days, starting from the first day after the transplantation. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels of the rats were measured 3 days before and at 1, 3, 5, 7, 10, and 14 days after the transplantation, and the survival time of the rats within 14 days were recorded. Immunohistochemical staining was used to examine the expressions of CD3 and Foxp3 in the liver graft, and acute graft rejection was assessed using HE staining based on the Banff schema.

Three rats in the control group died within 14 days after the surgery, while no death occurred in the AZD2014 group, demonstrating a significantly longer survival time of the rats in AZD2014 group (χ

=4.213,

=0.04). Serum ALT, AST and TBIL levels in the control group increased progressively after the surgery and were all significantly higher than those in AZD2014 group at the same time point (

< 0.05). Pathological examination revealed significantly worse liver graft rejection in the control group than in AZD2014 group based on assessment of the rejection index (

< 0.01); the rats in the control group showed more serious T lymphocyte infiltration and significantly fewer Treg cells in the liver graft than those in AZD2014 group (

< 0.01).

AZD2014 can effectively inhibit acute graft rejection in rats with allogeneic liver transplantation.

AZD2014 can effectively inhibit acute graft rejection in rats with allogeneic liver transplantation.

To evaluate the impact of a history of vaginal delivery on anesthesia management of patients undergoing hysteroscopic surgery under intravenous general anesthesia without tracheal intubation.

Ninety-nine patients undergoing hysteroscopic surgery under intravenous general anesthesia were enrolled in this study, including 43 patients with (VD group) and 56 patients without a history of vaginal delivery (NVD group). For all the patients, blood pressure, heart rate (HR), blood oxygen saturation (SpO

) and bispectral index (BIS) were recorded before anesthesia (T1), after anesthesia (T2), after cervical dilation (T3), and at 3 min after cervical dilation (T4). Propofol and etomidate doses during anesthesia induction, the total dose of propofol administered, additional intraoperative bolus dose and times of propofol, intraoperative body movement, total operation time and surgeons' satisfaction feedback scores were compared between the two groups. The postoperative awake time, recovery time, VAS score at 30 minvenous general anesthesia without tracheal intubation in terms of hemodynamic changes, anesthetic medication, and postoperative recovery quality, suggesting the necessity of individualized anesthesia management for these patients.

A history of vaginal delivery has a significant impact on anesthesia management of patients undergoing hysteroscopic surgery under intravenous general anesthesia without tracheal intubation in terms of hemodynamic changes, anesthetic medication, and postoperative recovery quality, suggesting the necessity of individualized anesthesia management for these patients.

To explore the effect of inhibiting polyribonucleotide nucleotidyl-transferase 1 (PNPT1) on oxygen-glucose deprivation (OGD)-induced apoptosis of mouse atrial myocytes.

Cultured mouse atrial myocytes (HL-1 cells) with or without OGD were transfected with PNPT1-siRNA or a negative control siRNA (NC-siRNA group), and the cell survival rate was detected using CCK-8 assay. The expression levels of ACTB and TUBA mRNA were detected with qPCR, and the protein expression of PNPT1 was detected with Western blotting. The apoptosis rate of the treated cells was determined with flow cytometry, the mitochondrial membrane potential was detected using JC-1 kit, and the mitochondrial morphology was observed using transmission electron microscope.

With the extension of OGD time, the protein expression levels of PNPT1 increased progressively in the cytoplasm of HL-1 cells (

< 0.05). Transfection with PNPT1-siRNA significantly reduced PNPT1 expression in HL-1 cells (

< 0.05). Exposure to OGD significantly enhanced degradation of ACTB and TUBA mRNA (

< 0.05) and markedly increased the apoptosis rate of HL-1 cells (

< 0.05), and these changes were significantly inhibited by transfection with PNPT1-siRNA (

< 0.05), which obviously increased mitochondrial membrane potential and improved mitochondrial morphology of HL-1 cells exposed to OGD.

Inhibition of PNPT1 improves mitochondrial damage and reduces degradation of apoptotic-associated mRNAs to alleviate OGD-induced apoptosis of mouse atrial myocyte.

Inhibition of PNPT1 improves mitochondrial damage and reduces degradation of apoptotic-associated mRNAs to alleviate OGD-induced apoptosis of mouse atrial myocyte.