Oleanolic acid inhibits cervical cancer Hela cell proliferation through modulation of the ACSL4 ferroptosis signaling pathway.

Cervical cancer remains the leading cause of cancerous death among women worldwide. Oleanolic acid (OA) is a substance that occurs naturally in the leaves, fruits, and rhizomes of plants and has anti-cancer activity. In this study, tumor-bearing mice were used as the animal model and Hela cells were used as cellular model. In vivo experiments have showed that OA significantly reduced the size and mass of cervical cancer tumors in mice. In vitro experiments have showed that OA significantly reduced the viability and proliferative capacity of Hela cells. In both in vivo and in vitro assays, OA increased the oxidative stress levels and Fe2+ content, and increased the expression of ferroptosis-related proteins. We found that ACSL4 was highly expressed in both xenograft models and cervical carcinoma cells with OA treatment. Further use of siRNA to interfere with ACSL4 expression in cervical cancer cells revealed that the inhibitory effect of OA on cell viability and proliferative capacity was counteracted, while a decrease in ROS levels and GPX4 was detected, suggesting that OA activated ferroptosis in Hela cells by promoting ACSL4 expression, thereby reducing the survival rate of Hela cells. Therefore, promotion of ACSL4-dependent ferroptosis by OA may be a potential approach for the treatment of cervical cancer.

Elevated plasma phage load as a marker for intestinal permeability in leukemic patients.

Microbial translocation (MT) and altered gut microbiota have been described in acute leukemic patients and contribute to immune activation and inflammation. However, phage translocation has not been investigated in leukemia patients yet. We recruited 44 leukemic patients and 52 healthy adults and quantified the levels of 3 phages in peripheral blood, which were the most positive phages screened from fecal samples. The content of 16S rRNA in plasma was detected by qPCR to assess the intestinal mucosa of these patients. Spearman's rank correlation was used to analyze the relationship between phage load and the relevant clinical data. We found the most prevalent phages in fecal samples were λ phage, Wphi phage, and P22 phage, and λ phage had the highest detection rate in plasma (68%). Phage content was affected by chemotherapy and course of disease and correlated with the levels of CRP (r = 0.43, p = 0.003), sCD14 (r = 0.37, p = 0.014), and sCD163 (r = 0.44, p = 0.003). Our data indicate that plasma phage load is a promising marker for gut barrier damage and that gut phage translocation correlates with monocyte/macrophage activation and systemic inflammatory response in leukemic patients.

Integrated microRNA and mRNA sequencing analysis of age-related changes to mouse thymic epithelial cells.

MicroRNAs (miRNAs) play key roles in the regulation of gene expression during multiple physiological processes, including early development, differentiation, and ageing. However, their involvement in age-related thymic involution is not clear. In this study, we profiled the global transcriptome and miRNAome of thymic epithelial cells in 1- and 3-month-old male and female mice, and predicted the possible transcription factors and target genes of the four most significantly differentially expressed miRNAs (DEMs) (miR-183-5p, miR-199b-5p, miR-205-5p, and miR-200b-3p) by performing bioinformatics analyses. We also evaluated the relationships between the significantly DEMs and mRNAs. We performed quantitative polymerase chain reaction to confirm the changes in the expression of the miRNAs and their predicted target genes. We found that miR-183-5p, miR-199b-5p, miR-205-5p, and miR-200b-3p can be used as a biomarker group for mouse thymus development and involution. In addition, the predicted target genes (Ptpn4, Slc2a9, Pkib, Pecam1, and Prkdc), which were identified by mRNA sequencing analysis, were mainly involved in growth, development, and accelerated senescence. In conclusion, miRNAs and their predicted target genes likely play important roles in thymus development and involution. To the best of our knowledge, this is the first study to systematically analyze the relevance of miRNAs and their targets by mRNA sequencing in mouse thymic epithelial cells. © 2018 IUBMB Life, 70(7):678-690, 2018.

Effect of Dongchongxiacao (Cordyceps) therapy on contrast-induced nephropathy in patients with type 2 diabetes and renal insufficiency undergoing coronary angiography.

OBJECTIVE: To study the protective effects of Dongchongxiacao (Cordyceps) (DCXC) on contrast-induced nephropathy (CIN) in patients with type 2 diabetes and renal insufficiency undergoing coronary angiography. METHODS: A total of 120 patients with type 2 diabetes whose estimated glomerular filtration rater (eGFR) was 60 mL/min · 1.73 in2, were divided randomly into three groups, basic treatment group (n = 41), standard DCXC therapy group (n = 39, 2-g corbrin capsules, 3 times/d, 3 days before and after angiography), and intensive DCXC therapy group (n = 40, 3-g corbrin capsules, 3 times/d, 3 days before and after angiography). Serum creatinine (cr) and eGFR were assessed at the time of admission to hospital, and on days 1, 2 and 3 after angiography. Urine neutrophil-gelatinase-associated-lipo- calin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) were measured before angiography and at day 1 after angiography for all patients. The primary end point was the prevalence of CIN. The secondary end point was a 25% or greater reduction in eGFR. RESULTS: CIN occurred in 11 of 120 patients (9.17 %). The prevalence of CIN was lower in the DCXC treatment groups than in the basic treatment group (P < 0.05), with a more significant decrease in the prevalence of CIN in the intensive DCXC therapy group (P < 0.01). Compared with the basic treatment group, a lower proportion of patients in the DCXC treatment groups had an eGFR decrease of 25% or greater (P < 0.05); patients with an eGFR decrease of 25% or greater accounted for an even lower proportion in the intensive DCXC therapy group (P < 0.01). Within 1 day of the procedure, urine levels of KIM-1, NGAL and IL-18 in patients in the intensive DCXC therapy group were lower than those in the basic treatment group and standard therapy group (P < 0.05). CONCLUSION: DCXC treatment may protect against CIN in patients with type 2 diabetes and renal insufficiency undergoing coronary angiography, with intensive DCXC therapy being more effective.

The effect of row structure on soil moisture retrieval accuracy from passive microwave data.

Row structure causes the anisotropy of microwave brightness temperature (TB) of soil surface, and it also can affect soil moisture retrieval accuracy when its influence is ignored in the inversion model. To study the effect of typical row structure on the retrieved soil moisture and evaluate if there is a need to introduce this effect into the inversion model, two ground-based experiments were carried out in 2011. Based on the observed C-band TB, field soil and vegetation parameters, row structure rough surface assumption (Q p model and discrete model), including the effect of row structure, and flat rough surface assumption (Q p model), ignoring the effect of row structure, are used to model microwave TB of soil surface. Then, soil moisture can be retrieved, respectively, by minimizing the difference of the measured and modeled TB. The results show that soil moisture retrieval accuracy based on the row structure rough surface assumption is approximately 0.02 cm(3)/cm(3) better than the flat rough surface assumption for vegetated soil, as well as 0.015 cm(3)/cm(3) better for bare and wet soil. This result indicates that the effect of row structure cannot be ignored for accurately retrieving soil moisture of farmland surface when C-band is used.

Characterization of Conductive 3D Printed Fingertips Manufactured by Fused Filament Fabrication.

This study purposed to develop conductivity 3D printed (3DP) fingertips and confirm their potential for use in a pressure sensor. Index fingertips were 3D printed using thermoplastic polyurethane filament with three types of infill patterns (Zigzag (ZG), Triangles (TR), Honeycomb (HN)) and densities (20%, 50%, 80%). Hence, the 3DP index fingertip was dip-coated with 8 wt% graphene/waterborne polyurethane composite solution. The coated 3DP index fingertips were analyzed by appearance property, weight changes, compressive property, and electrical property. As results, the weight increased from 1.8 g to 2.9 g as infill density increased. By infill pattern, ZG was the largest, and the pick-up rate decreased from 18.9% for 20% infill density to 4.5% for 80% infill density. Compressive properties were confirmed. Compressive strength increased as infill density increased. In addition, the compressive strength after coating was improved more than 1000 times. Especially, TR had excellent compressive toughness as 13.9 J for 20%, 17.2 J for 50%, and 27.9 J for 80%. In the case of electrical properties, the current become excellent at 20% infill density. By infill patterns at 20% infill density, TR has 0.22 mA as the best conductivity. Therefore, we confirmed the conductivity of 3DP fingertips, and the infill pattern of TR at 20% was most suitable.

Grassroots autonomous organizations embedding, non-agricultural employment and farmer homestead withdrawal behavior: based on the research data of Qionglai City, Sichuan Province, China.

In the context of the rapid rise of the village revitalization in China, the study examines the impact of grassroots autonomous organizations embedding level and farmer non-agriculture employment on the farmer homestead exit behavior. Based on 421 household surveys in Qionglai, this study obtained three results through empirical analysis. (1) The system embedding level of grassroots autonomous organization and the interests embedding level of grassroots autonomous organization have a significant positive impact on the farmer homestead withdrawal behavior, but the emotion embedding level of grassroots autonomous organizations has a significant negative impact on the farmer homestead withdrawal behavior. (2) The farmer non-agriculture employment level is beneficial for the farmer homestead exit behavior. (3) Further mechanism analysis shows that the non-agricultural employment level plays an inhibitory role in the positive influence of grassroots organizations to mobilize farmers to exit homestead. Therefore, it is suggested that when mobilizing farmers to voluntarily withdraw from the homestead, grassroots organizations should actively improve their embedding level, improve the construction of farmers' social network, and accelerate the accumulation of farmers' material capital.

Plasma Phage Load is Positively Related to the Immune Checkpoints in Patients Living with Human Immunodeficiency Virus.

BACKGROUND: Microbial Translocation (MT) and altered gut microbiota are involved in immune activation and inflammation, whereas immune checkpoint proteins play an important role in maintaining immune self-tolerance and preventing excessive immune activation. OBJECTIVE: This study aims to investigate the relationship between plasma phage load and immune homeostasis in people living with HIV(PLWH). METHODS: We recruited 15 antiretroviral therapy (ART)-naive patients, 23 ART-treated (AT) patients, and 34 Healthy Participants (HP) to explore the relationship between the plasma phage load and immune checkpoint proteins. The Deoxyribonucleic Acid (DNA) load of the lambda (λ) phage was detected using fluorescence quantitative Polymerase Chain Reaction (PCR). The Immune Checkpoints (ICPs) were detected using multiplex immunoassay. RESULTS: Our study demonstrated that the plasma phage load was increased in people living with HIV (PLWH) (P<0.05), but not in the ART-naive and AT groups (P>0.05). Plasma ICPs, including cluster of differentiation 27 (CD27), soluble glucocorticoid-induced Tumor Necrosis Factor (TNF) receptor (sGITR), soluble cluster of differentiation 80 (sCD80), sCD86, soluble glucocorticoidinduced TNF receptor-related ligand (sGITRL), soluble induced T-cell Costimulatory (sICOS), sCD40, soluble toll-like receptor 2 (sTLR2), and sCD28, were markedly decreased among the ARTnaive group (P<0.05) but not in the AT and HP groups (P>0.05). The plasma phage load was positively correlated with ICP and C-reactive protein (CRP) levels in PLWH (P<0.05). CONCLUSION: Our study indicated that the plasma phage load in PLWH was positively related to the expression of ICPs and inflammation, which may be used as a promising marker for the immune level of PLWH.

Higher Red Blood Cell Distribution Width is a Poor Prognostic Factor for Patients with Chronic Myeloid Leukemia.

PURPOSE: Red blood cell distribution width (RDW) has been considered as a potential indicator of the effects of treatment or as a prognostic indicator for various malignancies. Most chronic myeloid leukemia (CML) patients are in the chronic phase, but some have transformed to accelerated phase or blast phase (blast crisis). However, the clinical significance of RDW in CML remains limited. PATIENTS AND METHODS: In the present study, detailed clinical information and the RDW of 168 healthy people and 153 CML patients (106 patients for the training cohort and 47 patients for the validation cohort) were retrospectively assessed. RESULTS: Multivariate analysis demonstrated that patient age (OR, 1.081; 95CI% 1.039~1.125; p < 0.001), platelet counts (OR, 0.997; 95CI% 0.994~0.999; p = 0.001) and RDW at admission (OR,1.469; 95CI% 1.121~1.925; p = 0.005) were significantly associated with the patients with advanced phase. Among CML patients in the chronic phase, higher RDW was significantly associated with overall survival (OS; p = 0.0008) and the event-free survival (EFS; p = 0.0221) among CML patients with chronic phase, but not with Transformation-free survival (TFS; p = 0.0821). Furthermore, higher RDW was associated with higher mortality compared to patients with low RDW (CML-associated deaths; p < 0.0001). In addition, a decline in RDW is associated with the treatment of CML patients with tyrosine kinase inhibitors, especially at 6 and 12 months after the start of treatment. CONCLUSION: Higher RDW is a potential prognostic biomarker for chronic CML patients.

2-Chloro-4-fluoro-N-phenyl-benzamide.

In the title compound, C(13)H(9)ClFNO, the dihedral angle between the two aromatic rings is 13.6 (2)°. In the crystal, the mol-ecules are linked by inter-molecular N-H⋯O hydrogen bonds into chains extending along the c-axis direction.

3,6-Dichloro-N-(4-fluoro-phen-yl)picolinamide.

In the title compound, C(12)H(7)Cl(2)FN(2)O, the dihedral angle between the phenyl and pyridine rings is 42.5 (2) Šand an intramolecular N-H⋯N hydrogen bond occurs. The crystal structure is stabilized by C-H⋯O, C-H⋯F and C-Cl short contacts.

Effect of Faeces Bombycis Extract on Cajal Interstitial Cells in Diabetic Gastroparesis Rats Based on PI3K/Akt/mTOR Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic mechanism of Faeces Bombycis on diabetic gastroparesis （DGP） rats based on phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein （PI3K/Akt/mTOR） signaling pathway. MethodDGP rat model was prepared by random selection of 15 out of 105 rats as blank group. The rats successfully constructed were randomly divided into model group， high-，medium- and low- dose groups （3.2， 1.6， 0.8 g·kg-1） and moxapride group （1.5 mg·kg-1）， with 12 rats in each group， and were given gavage for 4 weeks. The gastric emptying rate and random blood glucose were measured. The morphological changes of gastric antrum were observed by hematoxylin-eosin （HE） staining， and the expression of the c-Kit gene was analyzed by immunohistochemistry. The apoptosis of Cajal interstitial cells was observed by in situ end labeling （TUNEL） staining， and the protein expressions of PI3K， phosphorylation（p）-PI3K， Akt， p-Akt， mTOR， and p-mTOR were detected by Western blot. ResultCompared with the blank group， the gastric emptying rate of the model group decreased significantly （P<0.01）， and the glandular structure of the gastric antrum was destroyed. The expression of c-Kit decreased （P<0.01）， and the apoptosis of Cajal interstitial cells （ICC） increased. Compared with the model group， the gastric emptying rate in the high， middle， and low-dose groups of Faeces Bombycis extract and mosapride group increased significantly （P<0.01）. The glandular structure of the gastric antrum became closer， and the apoptosis of ICC decreased. The expression of c-Kit in the high dose group of Faeces Bombycis extract increased significantly. After Western blot testing， compared with the blank group， the protein expression of p-Akt/Akt， p-PI3K/PI3K， and p-mTOR/mTOR in the model group increased. Compared with the model group， the protein expression of p-Akt/Akt in the high dose group of Faeces Bombycis extract decreased （P<0.01）， and the protein expression of p-PI3K/PI3K decreased in the middle and low dose groups of Faeces Bombycis extract and mosapride group decreased （P<0.05， P<0.01）. The protein expression of p-mTOR/mTOR decreased in the low dose group of Faeces Bombycis extract （P<0.05）. In terms of random blood glucose， compared with the blank group， the random blood glucose in the model group increased significantly （P<0.01）， and compared with the model group， the random blood glucose in the high and middle dose groups of Faeces Bombycis extract decreased significantly （P<0.05）. Compared with mosapride group， the protein expression of p-Akt/Akt decreased in the high dose group of Faeces Bombycis extract （P<0.05）， and the protein expression of p-PI3K/PI3K increased in the high， middle， and low dose groups of Faeces Bombycis extract （P<0.05， P<0.01）. ConclusionFaeces Bombycis extract can increase gastric emptying rate， reduce ICC apoptosis， and lower random blood glucose in DGP rats. The high dose group of Faeces Bombycis extract has a significant effect on inhibiting ICC apoptosis， and its mechanism may be related to the regulation of the PI3K/Akt/mTOR signaling pathway.

Establishment and evaluation of induced model of meibomian gland dysfunction in rats through eyeliner tattoo / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To establish a model of meibomian gland dysfunction in rats induced by eyeliner tattoo and investigate its potential mechanisms.METHODS:A total of 40 SD rats were selected, with 30 randomly chosen to have eyeliner tattoo applied their right eyes and designated as the eyeliner group. The remaining 10 rats were not given any treatment and served as the normal group. The corneal morphology of both groups was observed using a slit lamp at 1, 2, and 4 wk after establishment, and the tear film break-up time(BUT), Schirmer I test(SIt), corneal fluorescein staining score, and corneal irregularity score were calculated. The corneal Placido rings were examined using an ocular surface analyzer, and the corneal tissue structures of both groups were observed under a confocal microscope. After 4 wk and completion of clinical indicator recording, the eyeballs and upper and lower eyelid tissues were taken for pathological examination. The meibomian gland structures were observed through HE staining, the conjunctival goblet cells were observed using PAS staining, and the lipid droplets were observed with ORO staining.RESULTS:The slit lamp examination results showed that the eyeliner group rats exhibited in situ black pigmentation in the eyelids, with no eyelid deformation or scarring. The corneal epithelium was rough, with positive fluorescein staining, presenting as spotty staining that worsened over time. Compared with the normal group, the BUT was significantly shortened, tear secretion volume was significantly decreased, and the corneal fluorescein staining score and corneal irregularity score were significantly increased at 1, 2, and 4 wk after modeling in the eyeliner group(all P&#x003C;0.01). The corneal confocal microscopy results showed a decrease in corneal epithelial cells in the eyeliner group, with the appearance of abnormally bright cells, and inflammatory cell infiltration visible in the stromal layer. The ORO staining results revealed a decrease in lipid droplets in the eyeliner group, showing a downward trend with increasing observation time. The HE staining results showed that pigment blocked the meibomian gland openings in the eyeliner group, and the density of meibomian gland acini showed a downward trend over time. The PAS staining results showed a decreasing trend in the number of PAS-positive cells in the eyeliner group.CONCLUSION:Eyeliner tattoo can induce meibomian gland dysfunction, and the blockage of meibomian gland openings caused by the pigment particles used may be an important cause of meibomian gland dysfunction.

Cardiac MR tissue tracking technique for quantitatively evaluating myocardial strain of cardiac amyloidosis patients / 中国介入影像与治疗学

Objective To observe the feasibility of cardiac MR tissue tracking(CMR-TT)technique for quantitatively evaluating myocardial strain of patients with myocardial amyloidosis(CA).Methods Cardiac MRI were collected from 20 patients of immunoglobulin amyloid light-chain CA(AL-CA,group A),20 cases of transthyretin CA(ATTR-CA,group B)and 20 healthy subjects(group C),and myocardial strain parameters were obtained using CMR-TT technique.Left ventricular cardiac function parameters were compared among 3 groups,so were strain parameters of each myocardial segment of left ventricle and global myocardium,including 3D longitudinal strain(LS),3D radial strain(RS)and 3D circumferential strain(CS).Results Compared with those in group C,significant differences of left ventricular cardiac function parameters were found in both group A and B(all P＜0.01),while no statistical difference was found between group A and B(all P＞0.05).Except for apical segment RS(P=0.81),strain parameters in group A and B were both lower than those in group C(all P＜0.01),while no significant difference was detected between group A and B(all P＞0.05).Conclusion CMR-TT technique could be used to quantitatively evaluate left ventricular myocardial strain of CA patients.

Tris[6-(3,5-dimethyl-1H-pyrazol-1-yl)picolinato]gadolinium(III) methanol hemisolvate 2.5-hydrate.

In the title complex, [Gd(C(11)H(10)N(3)O(2))(3)]·0.5CH(4)O·2.5H(2)O, the Gd atom is coordinated by six N atoms and three O atoms derived from three tridentate monoanionic 6-(3,5-dimethyl-1H-pyrazol-1-yl)picolinate ligands. The mol-ecules are linked together via hydrogen bonds involving the solvent water and methanol mol-ecules.

Diaqua-bis[6-(3,5-dimethyl-1H-pyrazol-1-yl)picolinato-κN,N',O](nitrato-κO,O')lanthanum(III) monohydrate.

In the title complex, [La(C(11)H(10)N(3)O(2))(2)(NO(3))(H(2)O)(2)]·H(2)O, the La atom is coordinated by four N atoms and six O atoms derived from two 6-(3,5-dimethyl-1H-pyrazol-1-yl)picolinate ligands, one nitrate anion and two water mol-ecules. The mol-ecules are linked together via hydrogen bonds involving the water mol-ecules, forming a three-dimensional network.

Aqua-tris[6-(3,5-dimethyl-1H-pyrazol-1-yl)picolinato]-κN,N',O;κO-dysprosium(III) trihydrate.

In the title complex, [Dy(C(11)H(10)N(3)O(2))(3)(H(2)O)]·3H(2)O, the Dy(III) atom is coordinated by four N atoms and four O atoms derived from three tridentate deprotonated 6-(3,5-dimethyl-1H-pyrazol-1-yl)picolinate ligands and one water mol-ecule. The complex and solvent water mol-ecules are linked together via O-H⋯O, O-H⋯N, C-H⋯O and C-H⋯π hydrogen-bonding inter-actions, forming a three-dimensional network structure.

Bis[6-(3,5-dimethyl-1H-pyrazol-1-yl)picolinato-κN,O]cadmium(II) 1.75-hydrate.

In the title complex, [Cd(C(11)H(10)N(3)O(2))(2)]·1.75H(2)O, the Cd atom is coordinated by four N atoms and two O atoms from two tridentate 6-(3,5-dimethyl-1H-pyrazol-1-yl)picolinate ligands in a distorted cis-N(4)O(2) octa-hedral geometry. Three water mol-ecules, with occupancies of 1.0, 0.5 and 0.25, complete the asymmetric unit. The components of the crystal structure are linked via hydrogen bonds, forming a three-dimensional network.

Diagnosis and treatment of acute kidney injury after liver transplantation / 器官移植

Acute kidney injury is a common complication after liver transplantation, which severely affects clinical prognosis of liver transplant recipients. Multiple factors before, during and after liver transplantation may cause kidney injury. If not properly treated, it may progress into chronic kidney diseases, which significantly increases postoperative fatality and negatively affects clinical efficacy of liver transplantation. Therefore, prevention, diagnosis and treatment of acute kidney injury after liver transplantation is a hot topic for clinicians. In this article, the definition, diagnosis, risk factors, prevention and treatment of acute kidney injury after liver transplantation were reviewed, and potential risk factors and related therapeutic strategies during different stages of acute kidney injury after liver transplantation were analyzed, aiming to lower the risk of acute kidney injury after liver transplantation and further improve clinical prognosis of liver transplant recipients by optimizing treatment regimens.

Research progress on"one-two punch"strategy in the therapy of glioma / 中国肿瘤临床

Glioblastoma(GBM)originates from glial cells,and complete surgical resection followed by radiotherapy and chemotherapy is the current standard treatment.However,gliomas are subjected to not only accelerated cell death after radiotherapy and chemotherapy but also cellular senescence.Senescent cells produce a senescence-associated secretory phenotype(SASP),which has a dual effect on the tumor microenvironment.The"one-two punch"strategy of specifically eliminating senescent cells and inhibiting SASP-derived secretions provides a new direction for tumor therapy.In this article,we review the mechanisms that mediate tumor cellular senescence and SASP,the elimina-tion of senescent cells by senolytics for SASP inhibition,and the current situation of the"one-two punch"strategy for the treatment of glioma.