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Burkholderia pseudomallei is the causal agent of melioidosis, a deadly tropical infectious disease that lacks a vaccine. On the basis of the attenuated Staphylococcus aureus RN4220-Δ agr (RN), we engineered the RN4220-Δ agr / pdhB-hcp1 strain (RN-Hcp1) to generate B. pseudomallei hemolysin-coregulated protein 1 (Hcp1)-loaded membrane vesicles ( hcp1 MVs). The immunization of BALB/c mice with hcp1 MVs mixed with adjuvant by a three-dose regimen increased the serum specific IgG production. The serum levels of inflammatory factors, including TNF-α and IL-6, in hcp1 MV-vaccinated mice were comparable with those in PBS-challenged mice. The partial adjuvant effect of staphylococcal MVs was observed with the elevation of specific antibody titer in hcp1 MV-vaccinated mice relative to those that received the recombinant Hcp1 protein (rHcp1) or MVs derived from RN strain ( Δagr MVs). The hcp1 MVs/adjuvant vaccine protected 70% of mice from lethal B. pseudomallei challenge. Immunization with hcp1 MVs only protected 60% of mice, whereas vaccination with rHcp1 or Δagr MVs conferred no protection. Moreover, mice that received hcp1 MVs/adjuvant and hcp1 MVs immunization had low serum TNF-α and IL-6 levels and no inflammatory infiltration in comparison with other groups. In addition, all surviving mice in hcp1 MVs/adjuvant and hcp1 MVs groups exhibited no culturable bacteria in their lungs, livers, and spleens five days postinfection. Overall, our data highlighted a new strategy for developing B. pseudomallei vaccine and showed that Hcp1-incorporated staphylococcal MV is a promising candidate for the prevention of acute melioidosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Li, Li, Zheng, Peng, Rao, Li, Zhou and Rao.)

Objective: To establish the Z -score equation of right pulmonary artery (RPA) segments for some valuable pulse-wave Doppler parameters (PWD) and estimate their reference ranges in normal fetuses., Methods: Two hundred and seventy-three normal singleton fetuses at 18-38 weeks were enrolled in this fetal echocardiography of a prospective cross-sectional study. The proximal, middle, and distal segments of RPA of pulsed-wave Doppler parameters, such as peak systolic velocity (PSV) and pulsation index (PI) were obtained by using fetal Doppler echocardiography. The mean and standard deviation (SD) of each parameter and gestational age (GA) were analyzed by regression, and the optimal model of Z -score was established., Results: There was a significant correlation between fetal pulmonary artery Doppler parameters and gestational age, during the whole pregnancy, PI showed a downward trend with the progress of gestational week, while PSV showed an upward trend. Whether it was the original data or the data converted for the normal distribution of Z -score, the model that best described the mean value of parameters was quadratic regression. The SDs for PSV of the middle segment was a linear equation, others were constants. From proximal to distal of RPA, PSV showed a decreasing trend while PI showed an increasing trend., Conclusion: Z -score models and reference values for some PWD parameters of three segments of RPA were proposed against GA, which may quantitatively assess the flow dynamics of fetal RPA and quantitatively assess fetal lung circulation development and hemodynamic changes.

Objectives: The aim of this study was to assess the characteristics of mitral annular plane systolic excursion (MAPSE) in different longitudinal directions in normal fetuses using a new method, automatic cardiac motion quantification (aCMQ)., Methods: A cross-sectional study was conducted in 164 fetuses with structurally normal hearts. The time-displacement curves of the septal mitral annulus (SMA) in three directions, including point A, B and C (MAPSE-SMA-A, MAPSE-SMA-B, MAPSE-SMA-C), were recorded by aCMQ. The time to peak (TTP) in three directions, including point A, B and C (TTP-SMA-A, TTP-SMA-B, TTP-SMA-C) were recorded. In the same way, various parameters of the lateral mitral annulus (LMA) were obtained including MAPSE-LMA-A, MAPSE-LMA-B, MAPSE-LMA-C, TTP-LMA-A, TTP-LMA-B and TTP-LMA-C. Free angle M-mode echocardiography (FAM) was used to obtain MAPSE of LMA (FAM-MAPSE). Finally, all the data were analyzed statistically., Results: MAPSE was positively correlated with gestational age, and the difference between the second- and third-trimester groups was statistically significant. MAPSE-LMA in point B and C were greater than those of SMA. MAPSE-LMA-C and MAPSE-SMA-A were the largest in three directions.The difference between point B and C were statistically significant ( p <  .05), with no significant difference at point A ( p  > .05). There was no significant difference found in all TTP (all p  > .05). The MAPSE-LMA-C was less than the FAM-MAPSE, and the differences were found significantly ( p  < .05), but there was better correlation ( p  < .05)., Conclusions: The longitudinal movement of the fetal mitral annulus is comprehensive, with multiple directions and different displacements. Perpendicular to the mitral annulus is the maximum displacement. It is positively related to the gestational age. From the second trimester, the longitudinal contraction of the left ventricle wall has good synchronization. It possesses clinical value in selecting different methods and parameters during evaluating left ventricular function.

In this work, sulfur quantum dots (TPA-SQDs) protected by terephthalic acid as a stabilizer were synthesized using a one-pot method. When excited at 310 nm, the synthesized TPA-SQDs solution emitted strong blue fluorescence at 428 nm, and the absolute quantum yield was as high as 85.99%. The proposed SQDs can be used as a fluorescent probe to specifically quench tartrazine (TZ), showing a good linear relationship (R 2  = 0.996) at TZ concentrations of 0.1-20 μM, with a detection limit of 39 nM. By analysing the fluorescence lifetime, UV-Vis absorption spectrum and zeta potential of the assay system, it can be speculated that the fluorescence quenching mechanism of TZ on TPA-SQDs is the inner filter effect (IFE). The proposed method was applied to the detection of TZ in vitamin water and orange juice, and the results were consistent with the determination results by high-performance liquid chromatography. The recoveries and relative standard deviations were 93.2-102.6% and 1.34-2.88%, respectively, which provided an alternative method for the determination of TZ in beverages or other food samples., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Surgery has been the primary treatment for breast cancer. However, instant postoperative complications, such as sleep disorder and pain, dramatically impair early postoperative quality of recovery, resulting in more extended hospital stays and higher costs. Recent clinical trials indicated that stellate ganglion block (SGB) could prolong sleep time and improve sleep quality in breast cancer survivors. Moreover, during the perioperative period, SGB enhanced the recovery of gastrointestinal functions in patients with laparoscopic colorectal cancer surgery and thoracolumbar spinal surgery. Furthermore, perioperative SGB decreased intraoperative requirements for anesthetics and analgesics in patients with complex regional pain syndrome. However, information is scarce regarding the effects of SGB on postoperative quality recovery in patients with breast cancer surgery. Therefore, we investigated the effects of SGB on the postoperative quality of recovery of patients undergoing breast cancer surgery. Sixty patients who underwent an elective unilateral modified radical mastectomy were randomized into two 30-patient groups that received either an ultrasound-guided right-sided SGB with 6 ml 0.25% ropivacaine (SGB group) or no block (control group). The primary outcome was the quality of postoperative recovery 24 hours after surgery, assessed with a Chinese version of the 40-item Quality of Recovery (QoR-40) questionnaire. Secondary outcomes were intraoperative requirements of propofol and opioids, rest pain at two, four, eight, and 24 hours after surgery, patient satisfaction score, and the incidence of postoperative abdominal distension. At 24 hours after surgery, global QoR-40 scores were higher in the SGB group than in the control group. Besides, in the SGB group, patients needed less propofol, had a lower incidence of postoperative abdominal bloating, and had higher satisfaction scores. Ultrasound-guided SGB could improve the quality of postoperative recovery in patients undergoing breast cancer surgery by less intraoperatively need for propofol and better postoperative recovery of sleep and gastrointestinal function., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xiuli Yang et al.)

Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the interim analysis results of an ongoing, open-label, single-arm, phase 1 clinical trial of CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers ( NCT03874897 ). The primary objective was safety after CT041 infusion; secondary objectives included CT041 efficacy, pharmacokinetics and immunogenicity. We treated 37 patients with one of three CT041 doses: 2.5 × 10 8 , 3.75 × 10 8 or 5.0 × 10 8 cells. All patients experienced a grade 3 or higher hematologic toxicity. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 94.6% of patients. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported. The overall response rate (ORR) and disease control rate (DCR) reached 48.6% and 73.0%, respectively. The 6-month duration of response rate was 44.8%. In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC., (© 2022. The Author(s).)

Chronic prostatitis is a very common and very difficult disease. Based on the mobile medical system, this paper carried out a correlation analysis on the psychological factors and the evaluation of premature ejaculation in patients with benign prostatic hyperplasia. The article first analyzes the application in the field of mobile medical and then introduces the prostate image segmentation method based on the geometric active contour model. The emergence of automatic organ tissue segmentation technology is timely; it can help clinicians save a lot of manual segmentation time and has better reversibility and objectivity, and the theory of curve evolution is analyzed. Finally, this paper introduces the experimental research object and purpose, makes a statistical analysis of the symptoms of benign prostatic hyperplasia, and compares the incidence of psychological symptoms in patients with prostatitis under different factors. The experimental results of this paper show that 90% of prostatitis patients have mild psychological problems, and 10% have moderate psychological problems. Among them, the main reason for the psychological disorder of patients is depression, for which we should strengthen the care for patients., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Xiaohui Peng and Min Fu.)

To realize the utilization of high-performance lithium-oxygen batteries (LOBs), a rational-designed cathode structure and efficient catalytic materials are necessary. However, side products accumulated during battery cycling seriously affects the performance. Designing a cathode catalyst that could simultaneously facilitate the catalytic efficiency of the main reaction and inhibit the side reactions will make great sense. Herein, NiCeO x was proposed for the first time as a bifunctional cathode catalyst material for LOBs. The combined action of NiO and CeO 2 components was expected to facilitate the decomposition of byproducts (e.g., Li 2 CO 3 ), increase the oxygen vacancy content in CeO 2 , and enhance the adsorption of oxygen and superoxide. NiCeO x nanorods (NiCeO x PNR) were prepared using electrospinning method. It showed a hollow and porous nanorod (PNR)-like structure, which provided a large number of catalytic active sites and facilitated the transport of reactants and the deposition of discharge products. As a result, a high specific discharge capacity (2175.9 mAh g -1 ) and a long lifespan (67 cycles at 100 mA g -1 with a limited capacity of 500 mAh g -1 ) were obtained.

Aresenic trioxide (ATO) is proven to be active against leukaemia cells by inducing apoptosis and differentiation. Even though ATO could effectively induce remissions of leukaemia cells, the drug resistance was observed occasionally. To further dissect the mechanism of ATO resistance, we selected the ATO-resistant SH-SY5Y cells and found that Bcl-2 controlled the sensitivity of ATO in SH-SY5Y cells. We report that necroptosis, autophagy, NF-ƘB and MAPK signalling pathway are not involved in ATO-induced apoptosis. Moreover, the ATO-resistant cells showed distinct mitochondrial morphology compared with that of ATO-sensitive cells. Intriguingly, nude mice-bearing ATO-sensitive cells derived xenograft tumours are more sensitive to ATO treatment compared with that of ATO-resistant cells. These data demonstrate that cancer cells can acquire the ATO-resistance ability by increasing the Bcl-2 expression., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Aim: This basic research aimed to detect the inner-correlation of EGF containing fibulin extracellular matrix protein 1 (EFEMP1), TIMP metallopeptidase inhibitor 3 (TIMP3), matrix metalloprotease 9 (MMP9), elastin (ELN) in direct inguinal hernia (IH), and their effect on fibroblasts motility., Methods: Transversalis fascia samples from 20 direct IH patients and 20 varicocele (served as controls) patients were collected for detecting EFEMP1, TIMP3, MMP9 and ELN expressions by immunohistochemistry assay. Fibroblasts L929 cells were transfected with EFEMP1 overexpression plasmid or knock-down plasmid to investigate the influence of EFEMP1 dysregulation on L929 cell migration, invasion, TIMP3, MMP9 and ELN expressions. Additionally, rescue experiments were performed by adding TIMP3 knockdown plasmid to the EFEMP1-overexpressed L929 cells., Results: Transversalis fascia EFEMP1, TIMP3 and ELN expressions were decreased, but MMP9 expression was increased in IH patients compared with controls. In IH patients, EFEMP1 was not correlated with TIMP3, but positively correlated with ELN and negatively correlated with MMP9; TIMP3 negatively correlated with MMP9, but positively correlated with ELN. Overexpression of EFEMP1 did not affect TIMP3 expression but increased ELN expression and decreased MMP9 expression in L929 cells. In addition, EFEMP1 suppressed L929 cell migration and invasion. The following rescue experiments indicated that silencing TIMP3 attenuated the effect of EFEMP1 overexpression on MMP9 and ELN expressions as well as the effect of EFEMP1 overexpression on cell migration and invasion in L929 cells., Conclusions: EFEMP1 is downregulated in direct IH, and it regulates ELN homoeostasis as well as fibroblast mobility via interacting with TIMP3.

Aprotic Li-O 2 batteries are regarded as the most promising technology to resolve the energy crisis in the near future because of its high theoretical specific energy. The key electrochemistry of a nonaqueous Li-O 2 battery highly relies on the formation of Li 2 O 2 during discharge and its reversible decomposition during charge. The properties of Li 2 O 2 and its formation mechanisms are of high significance in influencing the battery performance. This review article demonstrates the latest progress in understanding the Li 2 O 2 electrochemistry and the recent advances in regulating the Li 2 O 2 growth pathway. The first part of this review elaborates the Li 2 O 2 formation mechanism and its relationship with the oxygen reduction reaction/oxygen evolution reaction electrochemistry. The following part discusses how the cycling parameters, e.g., current density and discharge depth, influence the Li 2 O 2 morphology. A comprehensive summary of recent strategies in tailoring Li 2 O 2 formation including rational design of cathode structure, certain catalyst, and surface engineering is demonstrated. The influence resulted from the electrolyte, e.g., salt, solvent, and some additives on Li 2 O 2 growth pathway, is finally discussed. Further prospects of the ways in making advanced Li-O 2 batteries by control of favorable Li 2 O 2 formation are highlighted, which are valuable for practical construction of aprotic lithium-oxygen batteries., (© 2021 Wiley-VCH GmbH.)

TTK is an essential spindle assembly checkpoint enzyme in many organisms. It plays a central role in tumor cell proliferation and is aberrantly overexpressed in a wide range of tumor types. We recently reported on a series of potent and selective TTK inhibitors with strong antiproliferative activity in triple negative breast cancer (TNBC) cell lines ( 8 : TTK IC 50 = 3.0 nM; CAL-51 IC 50 = 84.0 nM). Inspired by previously described potent tricyclic TTK inhibitor 6 (TTK IC 50 = 0.9 nM), we embarked on a structure-enabled design and optimization campaign to identify an improved series with excellent potency, TTK selectivity, solubility, CYP inhibition profile, and in vivo efficacy in a TNBC xenograft model. These efforts culminated in the discovery of 25 (TTK IC 50 = 3.0 nM; CAL-51 IC 50 = 16.0 nM), which showed significant single-agent efficacy when dosed iv in a TNBC xenograft model without body weight loss.

Steroid receptor coactivators (SRCs) possess specific and distinct oncogenic roles in the initiation of cancer and in its progression to a more aggressive disease. These coactivators interact with nuclear receptors and other transcription factors to boost transcription of multiple genes, which potentiate cancer cell proliferation, migration, invasion, tumor angiogenesis and epithelial-mesenchymal transition (EMT). Targeting SRCs using small molecule inhibitors (SMIs) is a promising approach to control cancer progression and metastasis. By high-throughput screening analysis, we recently identified SI-2 as a potent SRC SMI. To develop therapeutic agents, SI-10 and SI-12, the SI-2 analogs are synthesized that incorporate the addition of F atoms to the SI-2 chemical structure. As a result, these analogs exhibit a significantly prolonged plasma half-life, minimal toxicity and improved hERG activity. Biological functional analysis showed that SI-10 and SI-12 treatment (5-50 nM) can significantly inhibit viability, migration and invasion of breast cancer cells in vitro and repress the growth of breast cancer PDX organoids. Treatment of mice with 10 mg/kg/day of either SI-10 or SI-12 was sufficient to repress the growth of xenograft tumors derived from MDA-MB-231 and LM2 cells. Furthermore, in spontaneous and experimental metastasis mouse models developed from MDA-MB-231 and LM2 cells, respectively, SI-10 and SI-12 effectively inhibited the progression of breast cancer lung metastasis. These results demonstrate that SI-10 and SI-12 are promising therapeutic agents and are specifically effective in blocking tumor metastasis, a key point in tumor progression to a more lethal state that results in patient mortality in the majority of cases.

Background: Fetal heart evaluation has been proven to have the utility in the differential diagnosis of cardiomyopathies or prediction of perinatal mortality in congenital heart disease. The purpose of this study is to introduce a novel method that can measure the global and regional longitudinal strain of left ventricle in fetuses, described as automated cardiac motion quantitation (aCMQ). Furthermore, to evaluate the feasibility and value of aCMQ., Methods: A cross-sectional study was conducted in 138 fetuses with normal heart structure, then were divided into four groups by gestational age, standard four-chamber view clips were collected, the global and segmental longitudinal peak systolic strain of the left ventricle were measured by aCMQ, interobserver and intraobserver variability was analyzed., Results: The success rate of aCMQ analysis was 90.6% (125/138). aCMQ can obtain more comprehensive data to evaluate fetal cardiac function by on-line analysis, including the left ventricular end-systolic volume (LVESV, 0.64 ± 0.16 ml), the left ventricular end-diastolic volume (LVEDV, 0.85 ± 0.35 ml), strain and so on. There was no significant correlation between the gestational age and the global and segmental longitudinal peak strain of the left ventricle (all p  > .05). The base and middle segmental strain values of left ventricular free wall were similar to those of the interventricular septum. No significant differences were found in base segments and middle segments for left ventricular free wall (LVLW) and the interventricular septum (IVS) ( p  > .05). The strain of the apex segment was higher than that of the base and middle segment ( p  < .05), and there were significant differences between the apex and the base and the middle ( p  < .05). Interobserver and intraobserver variability showed a small bias among the observers., Conclusions: The global and regional strain values of fetus have no correlation with gestational ages, and the strain values of apical segment are higher than those of basal and middle segments. The base and middle segmental strain values of left ventricular free wall were similar to those of the interventricular septum. aCMQ is a novel method of two dimensional speckle tracking echocardiography to assess the global and regional systolic function of fetuses. It's a feasible and reproducible approach to evaluate normal cardiac function of fetus quantitatively and may have potential in fetuses with congenital heart diseases.

Genetic dissection kernel weight-related traits is of great significance for improving wheat yield potential. As one of the three major yield components of wheat, thousand kernel weight (TKW) was mainly affected by grain length (GL) and grain width (GW). To uncover the key loci for these traits, we carried out a quantitative trait loci (QTL) analysis of an F 6 recombinant inbred lines (RILs) population derived from a cross of Henong 5290 (small grain) and 06Dn23 (big grain) with a 50 K single nucleotide polymorphism (SNP) array. A total of 17 stable and big effect QTL, including 5 for TKW, 8 for GL and 4 for GW, were detected on the chromosomes 1B, 2A, 2B, 2D, 4B, 5A, 6A and 6D, respectively. Among these, there were two co-located loci for three traits that were mapped on the chromosome 4BS and 6AL. The QTL on 6AL was the most stable locus and explained 15.4-24.8%, 4.1-8.8% and 15.7-24.4% of TKW, GW and GL variance, respectively. In addition, two more major QTL of GL were located on chromosome arm 2BL and 2DL, accounting for 9.7-17.8% and 13.6-19.8% of phenotypic variance, respectively. In this study, we found one novel co-located QTL associated with GL and TKW in 2DL, QGl.haaf-2DL.2 / QTkw.haaf-2DL.2 , which could explain 13.6-19.8% and 9.8-10.7% phenotypic variance, respectively. Genetic regions and linked markers of these stable QTL will help to further refine mapping of the corresponding loci and marker-assisted selection (MAS) breeding for wheat grain yield potential improvement.

Patients with schizophrenia have shown widespread white matter microstructural abnormalities and cognitive deficits, but the definitive relationship between white matter and cognitive performance remains unclear. In this study, we investigated the possible associations between white matter integrity and cognitive deficits in drug-naive first-episode schizophrenia (dn-FES) using diffusion tensor imaging (DTI). A total of 96 participants, including 46 dn-FES patients and 50 healthy individuals, underwent 3.0 T magnetic resonance diffusion-weighted imaging and cognitive assessments using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Group differences were tested using tract-based spatial statistics (TBSS). Compared with the control group, the dn-FES group exhibited reduced white matter integrity, as indexed using fractional anisotropy (FA) metrics, in the right-hemispheric cluster comprising the posterior thalamic radiation, posterior corona radiata, superior longitudinal fasciculus, retrolenticular part of the internal capsule, tapetum, splenium of the corpus callosum, sagittal stratum, and inferior longitudinal fasciculus. We found that social cognitive deficit is significantly correlated with reduced FA in these white matter regions, except the sagittal stratum and inferior longitudinal fasciculus. Furthermore, we found that speed of processing is positively correlated with reduced FA in the right superior longitudinal fasciculus of dn-FES patients. In summary, white matter deficits were validated in dn-FES patients and could be associated with speed of processing and social cognition, providing clues about a neural basis of schizophrenia and a potential biomarker for clinical studies., Competing Interests: None., (AJTR Copyright © 2020.)

At present, seeking an effective dressing for wound regeneration has drawn considerable interest. In this paper, a novel agarose-grafting-hyaluronan (Ag-g-HA) scaffold was synthesized for rapid wound healing. Elemental analysis results showed that the HA grafting rate of Ag-g-HA was ∼69%. Ag-g-HA remained bioactive to accelerate cell proliferation and stimulate secretion of TNF-α for macrophagocyte RAW 264.7, and collagen I and collagen III for fibroblast 3T3. An i n vivo study demonstrated that Ag-g-HA showed a faster repair cycle and a better skin histological structure for a full-thickness skin defect. The collagen I, collagen III and TNF-α secreted by mice for Ag-g-HA were similiar to HA. Ag-g-HA showed a similiar biological activity to HA but had a longer degradation time through its improved insolubility. These findings demonstrate that the Ag-g-HA scaffold accelerated wound healing, and could be a promising novel scaffold for tissue engineering and regenerative medicine.

Background: Sleep disorders are commonly encountered in clinic. Evidences showed that sleep deprivation may modulate the effectiveness of general anesthetics in rats. However, this phenomenon has not been explored in humans. The study aimed to investigate whether the hypnotic potency of sevoflurane in patients with sleep disorders differ from patients with normal sleep habits., Methods: We recruited 44 patients scheduled for elective breast surgery and eventually analyzed 38 patients, including 19 subjects with normal sleep habits and 19 subjects with sleep disorders. According to the Dixon 'up-and-down' design, patients received sevoflurane at preselected concentrations starting at 1.0 vol%. After a steady-state period, a verbal command for testing awakening was performed. Based on the negative or positive response to the verbal command, we decreased or increased the concentration of sevoflurane by 0.2 vol% in the next patient accordingly. Plasma orexin-A was also measured before observation., Results: The MACawake of sevoflurane was 0.80% [95% confidence interval (CI), 0.683-0.926%] in the sleep disordered group vs 0.60% [95% CI, 0.493-0.689%] in the control group. The relative median potency between groups was 0.750 (95% CI, 0.236-0.969). Patients with sleep disorders had significantly higher orexin-A levels than control (72.17 ± 18.24 vs. 36.16 ± 14.18 pg/mL). A significant, positive relationship was detected between orexin-A level and probability of awakening (OR = 1.081, 95% CI is 1.020-1.146, P = 0.008)., Conclusions: MACawake of sevoflurane is higher in mild-aged women of breast surgery with sleep disorders compared to those with normal sleep habits. The increased anesthetic requirement may be related to changes of orexin-A levels. These findings suggest that sleep may have a potential impact on clinical anesthesia, including changes of sensitivity to anesthetics or postoperative complications. Further research is needed to confirm this hypothesis., Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR1800016022), date of registration 07 May 2018.

In this study, we synthesized four novel Al 18/19 F-labeled 2-phenylbenzothiazole derivatives conjugated to 1,4,7-triazacyclononane-1,4-diacetic acid via alkyl linkers and evaluated them as imaging agent targets to amyloid-β (Aβ) plaques deposited in the blood vessels of cerebral amyloid angiopathy (CAA) brain. The four ligands exhibited moderate-to-high binding ability to Aβ 1-42 aggregates, of which complex 17 possessing the most potent affinity ( K i = 11.3 nM) was selected for further biological evaluations. In vitro fluorescent staining and in vitro autoradiography studies on brain sections from CAA patients proved that this ligand could label Aβ deposits in blood vessels selectively. In biodistribution study, [ 18 F] 17 can hardly penetrate the blood-brain barrier (brain 2 min = 0.3% ID/g) and displayed a rapid blood washout rate (blood 2 min /blood 60 min = 25.2), which is favorable as CAA imaging agents. In conclusion, this Al 18 F-labeled 2-phenylbenzothiazole complex was developed and proved to be a promising CAA positron emission tomography agent., Competing Interests: The authors declare no competing financial interest.

Aim: MicroRNAs (miRs) are endogenous substances that act as important diagnostic and treatment targets in renal diseases. miR-146 plays an important role in the development of endotoxin tolerance through NF-κB pathway, but the underlying mechanism is not clearly understood. The aim of this study was to determine the molecular regulation and function of miR-146 and also the expression of miR-146 in an experimental model of renal ischemia reperfusion injury (IRI)., Methods: IRI was induced in mouse by bilateral IRI for 45 min followed by reperfusion. The male mice were randomized as: sham, I/R, I/R+miR-146, and I/R+antago-miR-146 groups. Renal function, histological damage, and cell apoptosis were evaluated at 24 h after reperfusion., Results: Overexpression of miR-146 protected renal function. Renal cells with upregulated miR-146 had lower plasma levels of blood urea nitrogen (BUN) and creatinine, decreased apoptosis and active caspase-3 protein expressions. miR-146 was shown to have a role in renal IR injury. miR-146 has a protective effect on renal function and plays a significant role in apoptosis. IGSF1 acts as a target of miR-146. IGSF1 rescued the effects of miR-146 on renal IRI. miR-146 protected renal function by activation of PI3K/AKT., Conclusion: These findings suggest that miR-146 might regulate apoptosis and can cause injury in I/R via targeting IGSF1 and also exert renal protection property.

Although immune mechanisms can suppress tumour growth, tumours establish potent, overlapping mechanisms that mediate immune evasion. Emerging evidence suggests a link between angiogenesis and the tolerance of tumours to immune mechanisms. Hypoxia, a condition that is known to drive angiogenesis in tumours, results in the release of damage-associated pattern molecules, which can trigger the rejection of tumours by the immune system. Thus, the counter-activation of tolerance mechanisms at the site of tumour hypoxia would be a crucial condition for maintaining the immunological escape of tumours. However, a direct link between tumour hypoxia and tolerance through the recruitment of regulatory cells has not been established. We proposed that tumour hypoxia induces the expression of chemotactic factors that promote tolerance. Here we show that tumour hypoxia promotes the recruitment of regulatory T (T(reg)) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumour tolerance and angiogenesis. Thus, peripheral immune tolerance and angiogenesis programs are closely connected and cooperate to sustain tumour growth., (©2011 Macmillan Publishers Limited. All rights reserved)

Repair of bone defects of a critical size encounters many problems, and many efforts aim to build a porous scaffold loading bone marrow stromal cells (BMSCs) or bone morphogenetic protein (BMP2) to quickly repair bone defects. In this paper, a laminated scaffold was designed and tested for the repair of bone defects in a caprine tibia. Beta-tricalcium phosphate (β-TCP) and poly (L-lactic acid) (PLLA) were fabricated to a sandwich structured composite that was then rolled up to form a cylindrical shaped, porous scaffold. The porosity and bending strength of the PLLA/β-TCP laminated scaffold were around 70% and 1.7 MPa, respectively. Results from in vitro experiments showed that the pH value of the scaffold in water fluctuated between 4.9 and 7.0 during its degradation. When exposed to the simulated body fluid, the scaffold lost its strength after 11 weeks of degradation. After implantation in Chinese caprines' diaphyseal defects with loaded allogeneic BMSCs, the scaffold sped up the bone repair without collapse of the scaffold and the unwanted inflammatory response, and then rapidly degraded and finally disappeared at 12 weeks. Gross examinations and pullout tests showed that the experimental caprines walked normally and the implanted leg could be heavily loaded. X-ray examinations and histological analyses showed new bone tissues formed with similar structures to normal ones. It is suggested that the novel PLLA/β-TCP laminated scaffold with BMSCs loading can regenerate new bones quickly., (© 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

The use of infectious agents as vaccine adjuvants has shown utility in both prophylactic and therapeutic vaccinations. Listeria monocytogenes has been used extensively as a vaccine vehicle due to its ability to initiate both CD4(+) and CD8(+) immune responses. Previous work from this laboratory has used transgenic Listeria to deliver vaccine constructs. A chimeric protein composed of tumor antigen and a non-hemolytic variant of the Listeria protein, listeriolysin O (LLO), has demonstrated effective tumor protection beyond that of antigen alone expressed in the same system. To address the question of how fusion with LLO improves vaccine efficacy, we constructed a number of DNA plasmid vaccines to isolate this effect in the absence of other endogenous Listeria effects. Here we have analyzed the ability of these vaccines to induce the regression of previously established tumors. A vaccine strategy using DNA vaccines bearing the tumor antigen either alone or in combination with LLO in addition to plasmids encoding MIP-1alpha and GM-CSF was examined. Further, LLO was used either as a chimera or in a bicistronic construct to address the importance of fusion between these elements. Notably, the strategies employing both chimeric and bicistronic vaccines were effective in reducing tumor burden suggesting that LLO can act as an adjuvant that does not require fusion with the tumor antigen to mediate its effect.

Objective: To study the effects of astragalus membranaceus injection on sperm abnormality in Cd-induced rats., Methods: Thirty adult male Sprague-Dawley rats were divided into 5 groups: low concentration abstragalus membranaceus group(A1), high concentration astragalus membranaceus group(A2), cyclophosphamide group (CP), cadmium chloride group (Cd) and control group (C). Astragalus membranaceus injections 5 g/(kg.d) or 10 g/(kg.d) were given intraperitoneally to the rats of the A1, A2, CP and Cd groups. After 7 days, cadmium chloride(0.2 mg Cd/kg body weight) was administrated by intraperitoneal injection stimultaneously to the A1, A2 and Cd group rats. At 22 d after cadmium chloride induction, the rats were sacrificed and the testis coefficient, testicular sperm count, daily sperm production, epididymal sperm count and percentage of sperm abnorality were observed, and the testes and epididymides were studied pathologically., Results: Testis coefficient, testicular sperm count, daily sperm production and epididymal sperm count in the A2 group [(5.68 +/- 1.19), (49.01 +/- 8.78) x 10(6)/g, (10.25 +/- 2.30) x 10(6)/(g.d), (47.51 +/- 22.51) x 10(6)/ml] increased significantly compared with those of the Cd group [(3.11 +/- 0.16), (37.59 +/- 10.63) x 10(6)/g, (5.31 +/- 0.32) x 10(6)/(g.d), (10.89 +/- 2.45) x 10(6)/ml] (P < 0.05 or P < 0.01). The percentage of sperm abnormality in the A2 group [(7.04 +/- 0.12)%] decreased significantly compared with that of the Cd group [(17.81 +/- 1.55)%] (P < 0.01)., Conclusions: As an antimutagen astragalus membranaceus has practical value in occupational protection against Cd-induced genetic damage.

The induction of mucosal immunity is crucial in controlling viral replication during HIV infection. In this study we compare the ability of a recombinant Listeria monocytogenes that expresses and secretes the HIV Ag Gag to induce CD8(+) T cells against this Ag in the spleen, mesenteric lymph nodes, and Peyer's patches and the ability to provide effector Gag-specific CD8(+) T cells to the lamina propria after i.v., oral, or rectal administration of the vaccine. The levels of Ag-specific CD8(+)-activated T cells were measured ex vivo using intracellular cytokine staining for IFN-gamma and H-2K(d) Gag peptide tetramer staining. We found that all routes of immunization induced Gag-specific CD8(+) T cells in the spleen. After secondary infection, we observed substantial increases in splenic levels of CD8(+) T cells, and levels of Gag-specific cells were similar to those against listeriolysin O, the immunodominant Ag of L. monocytogenes. Both primary and secondary oral immunization resulted in abundant Gag-specific CD8(+)-activated T cells in the lamina propria that constituted approximately 35% of the CD8 compartment. However, significant levels of Gag and listeriolysin O-specific CD8(+) T cells were observed in mucosal lymphoid tissue only after two immunizations, perhaps because they had already entered the lamina propria compartment after a single immunization. In the context of HIV, a mucosally administered vaccine seems best calculated to prompt an immune response that is capable of preventing infection. The data presented in this report demonstrate that mucosally administered Listeria can prompt such a response and that booster doses can maintain this response.