A conserved ZFX/WNT3 axis modulates the growth and imatinib response of chronic myeloid leukemia stem/progenitor cells.

BACKGROUND: Zinc finger protein X-linked (ZFX) has been shown to promote the growth of tumor cells, including leukemic cells. However, the role of ZFX in the growth and drug response of chronic myeloid leukemia (CML) stem/progenitor cells remains unclear. METHODS: Real-time quantitative PCR (RT-qPCR) and immunofluorescence were used to analyze the expression of ZFX and WNT3 in CML CD34+ cells compared with normal control cells. Short hairpin RNAs (shRNAs) and clustered regularly interspaced short palindromic repeats/dead CRISPR-associated protein 9 (CRISPR/dCas9) technologies were used to study the role of ZFX in growth and drug response of CML cells. Microarray data were generated to compare ZFX-silenced CML CD34+ cells with their controls. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to study the molecular mechanisms of ZFX to regulate WNT3 expression. RT-qPCR and western blotting were used to study the effect of ZFX on ß-catenin signaling. RESULTS: We showed that ZFX expression was significantly higher in CML CD34+ cells than in control cells. Overexpression and gene silencing experiments indicated that ZFX promoted the in vitro growth of CML cells, conferred imatinib mesylate (IM) resistance to these cells, and enhanced BCR/ABL-induced malignant transformation. Microarray data and subsequent validation revealed that WNT3 transcription was conservatively regulated by ZFX. WNT3 was highly expressed in CML CD34+ cells, and WNT3 regulated the growth and IM response of these cells similarly to ZFX. Moreover, WNT3 overexpression partially rescued ZFX silencing-induced growth inhibition and IM hypersensitivity. ZFX silencing decreased WNT3/ß-catenin signaling, including c-MYC and CCND1 expression. CONCLUSION: The present study identified a novel ZFX/WNT3 axis that modulates the growth and IM response of CML stem/progenitor cells.

The correlation between nuts and algae-less diet and children's blood pressure: from a cross-sectional study in Chongqing.

BACKGROUND: Nuts and algae have been shown to improve BP levels, but their effectiveness is controversial. AIMS: This study aims to illustrate the effect of dietary pattern with nuts and algae-less on BP levels in children and adolescents from a cross-sectional study. METHODS: A total of 5645 children from the Chongqing Children's Health Cohort, aged 9.34 ± 1.74 years with 52.05% males, were analyzed. Stratified analysis was conducted to explore the differences between the two dietary patterns in urban or rural areas, as well as the differences in different gender. Logistic regression was used to analyze the influence factors of increased BP. And a GLM was used to analyze the influence of the two dietary patterns on systolic blood pressure (SBP, mmHg), diastolic blood pressure (DBP, mmHg), and mean arterial pressure (MAP, mmHg). RESULTS: Children with nuts and algae-less dietary patterns had higher SBP (104.68 ± 10.31 vs 103.81 ± 9.74, P = .006), DBP (64.27 ± 7.53 vs 63.55 ± 7.52, P = .002), and MAP (77.74 ± 7.75 vs 76.97 ± 7.52, P = .001) compared with those children with a balanced diet. After adjusting for covariates, the nuts and algae-less diet was a risk factor for hypertension in children when compared with the balanced diet(OR(95%CI):1.455(1.097,1.930), P = .009). The nuts and algae-less diet has a significant influence on SBP (104.68 ± 10.31 mmHg vs.103.81 ± 9.74 mmHg, P = .006). Stratified analysis by sex showed that nuts and algae-less dietary patterns had a more significant impact on females than males. CONCLUSION: Nuts and algae-less dietary pattern correlated with increased BP levels in children, and a greater impact on SBP levels was found in females, suggesting that a balanced diet with appropriate nuts and algae should be proposed for children in China.

[Time series analysis of fine particulate matter and death risk among residents in an urban area of Chongqing City in 2013-2020].

OBJECTIVE: To investigate the effects of the concentration of fine particulate matter(PM_(2.5)) on the risk of death among residents in an urban area of Chongqing, China. METHODS: Daily data on mean PM_(2.5) concentration, meteorological factors(air temperature and relative humidity), and the number of deaths from 2013 to 2020 in this urban area were collected. A generalized additive model was used to analyze the association of PM_(2.5) concentration with the number of deaths, and stratified analyses by sex and age were further performed. RESULTS: In this area from 2013 to 2020, the median concentration of atmospheric ambient PM_(2.5) was 44.00 µg/m~3; 48 089 non-accidental deaths, 19 252 deaths from circulatory diseases, and 8753 deaths from respiratory diseases were reported. The PM_(2.5) concentration was higher in winter and spring. The number of deaths showed no obvious seasonal changes. The time series analysis showed that for every 10 µg/m~3 increase in the PM_(2.5) concentration, the risks of non-accidental death(lag03), circulatory diseases-caused death(lag3), and respiratory diseases-caused death(lag03) increased by 0.64%(95% CI 0.07%-1.21%), 0.68%(95% CI 0.05%-1.32%) and 1.72%(95% CI 0.54%-2.90%), respectively. After adjusting for several gaseous pollutants(PM_(10), NO_2, O_3, SO_2 and CO), the impact of PM_(2.5) concentration on residents' health had no significant changes. The stratified analyses by sex and age showed that when the PM_(2.5) concentration increased, the risks of non-accidental death and death from respiratory diseases were higher in women and residents aged ≥65 years than in men and higher in residents aged ≥65 years than in those aged 5-64 years, but there were no significant differences between the groups. CONCLUSION: PM_(2.5) pollution may increase the risk of death for residents in this urban area in Chongqing.

Bacterial cell-body rotation driven by a single flagellar motor and by a bundle.

Using self-trapped Escherichia coli bacteria that have intact flagellar bundles on glass surfaces, we study statistical fluctuations of cell-body rotation in a steady (unstimulated) state. These fluctuations underline direction randomization of bacterial swimming trajectories and plays a fundamental role in bacterial chemotaxis. A parallel study is also conducted using a classical rotation assay in which cell-body rotation is driven by a single flagellar motor. These investigations allow us to draw the important conclusion that during periods of counterclockwise motor rotation, which contributes to a run, all flagellar motors are strongly correlated, but during the clockwise period, which contributes to a tumble, individual motors are uncorrelated in long times. Our observation is consistent with the physical picture that formation and maintenance of a coherent flagellar bundle is provided by a single dominant flagellum in the bundle.

Identification of Circ-FNDC3B, an Overexpressed circRNA in Abdominal Aortic Aneurysm, as a Regulator of Vascular Smooth Muscle Cells.

Circular RNAs (circRNAs) have been implicated in the dysfunction of vascular smooth muscle cells (VSMCs), which is linked with the development of abdominal aortic aneurysm (AAA). Herein, we explored the precise action of circRNA fibronectin type III domain containing 3B (circ-FNDC3B) in VSMC injury triggered by angiotensin II (Ang-II).Circ-FNDC3B, microRNA (miR) -143-3p, and a disintegrin and metalloproteinase 10 (ADAM10) were quantified by quantitative real-time polymerase chain reaction or western blot assay. Ribonuclease R and subcellular localization assays were applied to characterize circ-FNDC3B. Cell viability, apoptosis, and proliferation were assessed by the Cell Counting Kit-8 assay, flow cytometry, and 5-Ethynyl-2' -Deoxyuridine assay, respectively. The levels of tumor necrosis factor alpha, interleukin-6, superoxide dismutase, and malonaldehyde were estimated by enzyme-linked immunosorbent assay. Direct relationship miR-143-3p and circ-FNDC3B or ADAM10 was verified by dual-luciferase reporter and RNA immunoprecipitation assays.Circ-FNDC3B was highly expressed in AAA tissues and Ang-II-treated VSMCs. Knocking down circ-FNDC3B alleviated Ang-II-induced VSMC injury. Mechanistically, circ-FNDC3B directly targeted miR-143-3p, and miR-143-3p was a downstream mediator of circ-FNDC3B in regulating cell injury induced by Ang-II. ADAM10 was directly targeted and inhibited by miR-143-3p. MiR-143-3p-mediated inhibition of ADAM10 relieved Ang-II-induced VSMC injury. Furthermore, circ-FNDC3B acted as a competing endogenous RNA for miR-143-3p to modulate ADAM10 expression.Our findings suggested that circ-FNDC3B silencing ameliorated cytotoxicity triggered by Ang-II in VSMCs at least partially depending on the regulation of the miR-143-3p/ADAM10 axis.

MiR-205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression.

MicroRNAs (MiRNAs, MiRs) represent a class of conserved small non-coding RNAs that affect post-transcriptional gene regulation and play a vital role in angiogenesis, proliferation, apoptosis, migration and invasion. They are essential for a wide range of physiological and pathological processes, especially for vascular diseases. However, data concerning miRNAs in endothelial progenitor cells (EPCs) and deep vein thrombosis (DVT) remain incomplete. We explored miRNAs that modulate angiogenesis in EPCs and thrombolysis, and analysed their underlying mechanisms using a DVT model, dual-luciferase reporter assay, qRT-PCR, Western blot, immunofluorescence staining, flow cytometry analysis, CCK-8 assay, angiogenesis assay, wound healing and Transwell assay. We found that miR-205 enhanced the homing ability of EPCs to DVT sites and promoted thrombosis resolution and recanalization, which significantly reduced venous thrombus. Additionally, we demonstrated that miR-205 overexpression significantly enhanced angiogenesis in vivo and in vitro, migration, invasion, F-actin filaments and proliferation in EPCs, and inhibited cell apoptosis. Conversely, down-regulation of miR-205 played the opposite role in EPCs. Importantly, this study demonstrated that miR-205 directly targeted PTEN to modulate the Akt/autophagy pathway and MMP2 expression, subsequently playing a key role in EPC function and DVT recanalization and resolution. These results elucidated the pro-angiogenesis effects of miR-205 in EPCs and established it as a potential target for DVT treatment.

LncRNA WTAPP1 Promotes Migration and Angiogenesis of Endothelial Progenitor Cells via MMP1 Through MicroRNA 3120 and Akt/PI3K/Autophagy Pathways.

Efficient recruitment and angiogenesis of endothelial progenitor cells (EPCs) are critical during a thrombus event. However, the details of EPC recruitment and the regulation of angiogenesis have not been fully determined. The aim of this study was to determine the role of the long noncoding (lnc)RNA Wilms tumor 1 associated protein pseudogene 1 (WTAPP1) in regulation of the migration and angiogenesis of EPCs. EPCs were isolated from human peripheral blood and characterized by flow cytometry, after which lentivirus-mediated lncRNA WTAPP1 overexpression and knockdown were performed. Scratch assay, Transwell assay, and in vitro and in vivo tube formation assays were performed to measure cell migration, invasion, and angiogenic abilities, respectively. Moreover, a microarray screen, bioinformatic prediction, and quantitative PCR and Western blot of miRNAs interacting with lncRNA WTAPP1 were conducted. Western blot was carried out to elucidate the relationship among WTAPP1, miR-3120-5P, and MMP-1 in the autophagy pathway. WTAPP1 positively regulated migration, invasion, and in vitro and in vivo tube formation in EPCs by increasing MMP-1 expression and activating PI3K/Akt/mTOR signaling. Furthermore, WTAPP1 contains a putative miR-3120-5P binding site. Suppression of WTAPP1 by miR-3120-5P decreased the level of MMP-1. In addition, we demonstrated that suppression of the autophagy pathway is involved in the effects of WTAPP1 on EPC migration and angiogenesis. The lncRNA WTAPP1, a molecular decoy for miR-3120-5p, regulates MMP-1 expression via the PI3K/Akt and autophagy pathways, thereby mediating cell migration and angiogenesis in EPCs. Acting as a potential therapeutic target, the lncRNA WTAPP1 may play an important role in the pathogenesis of DVT. Stem Cells 2018;36:1863-12.

Rotating Bacteria on Solid Surfaces without Tethering.

Bacterial motion is strongly affected by the presence of a surface. One of the hallmarks of swimming near a surface is a defined curvature of bacterial trajectories, underlining the importance of counter rotations of the cell body and flagellum for locomotion of the microorganism. We find that there is another mode of bacterial motion on solid surfaces, i.e., self trapping due to fluid flows created by a rotating flagellum perpendicular to the surface. For a rod-like bacterium, such as Escherichia coli, this creates a peculiar situation in that the bacterium appears to swim along a minor axis of the cell body and is pressed against the surface. Although a full hydrodynamic theory is still lacking to explain the self-trapping phenomenon, the effect is intriguing and can be exploited to study a variety of biophysical phenomena of swimming bacteria. In particular, we showed that self-trapped E. coli cells display a chemotaxis response that is identical to the classical rotation assay in which antibodies are used to physically "glue" a flagellum to the surface.

Elevated Plasma Levels of Gas6 Are Associated with Acute Lung Injury in Patients with Severe Sepsis.

Acute lung injury (ALI) is one of the complications of severe sepsis, causing sudden deaths. However, information regarding predictive factors for the onset of ALI in severe sepsis is limited. Growth arrest-specific gene 6 (Gas6) is secreted by endothelial cells and is important for the activation of endothelium during inflammation. This study aimed to investigate the predictive effect of plasma Gas6 in patients with severe sepsis. Collection of plasma samples was carried out from 129 participants with severe sepsis following with or without ALI development. We found that the elevated levels of Gas6, interleukin-6 and -8 (IL-6 and IL-8) in plasma were associated with the ALI development (P = 0.003, 0.002, and 0.004, respectively). We also observed the robust correlation between the plasma level of Gas6 and the following ALI development to adjustment for sepsis and administration of vasopressor. Between patients with ALI (n = 18) and those without ALI (n = 111), Gas6 and the Lung Injury Prediction Score (LIPS) showed promising discrimination (AUROC, 0.74 and 0.68, respectively), and in combination with these two indexes, the AUROC was increased to 0.86 (vs. 0.74, P = 0.05), while soluble receptor for advanced glycation end products (sRAGE) and Willebrand factor (vWF) in plasma showed no predictive value for of ALI. Collectively, our findings indicate that higher levels of Gas6 in plasma are obviously correlated with ALI development. An early increase in the plasma Gas6 level suggests that endothelial injury is a key link in the pathogenesis of ALI.

ZFX modulates the growth of human leukemic cells via B4GALT1.

Zinc finger protein X-linked (ZFX) is a key regulator of both embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs), which is required for both Notch intracellular domain (NotchIC)-induced acute T-cell leukemia and MLL-AF9-induced myeloid leukemia in mouse models. However, the role of ZFX and its underlying mechanism in human leukemic cells remain unclear yet, though accumulating data have demonstrated that ZFX is aberrantly expressed in various human tumors and plays an important role. Herein, we found that ZFX was aberrantly expressed in various human leukemic cell lines and primary cells from leukemia patients compared with control cells. The silence of ZFX led to the growth suppression through either the deregulated cell cycle or the induction of apoptosis in various cells including K562, Jurkat, Namalwa, and THP-1 cells. The gene expression analysis revealed that UDP-Gal:ßGlcNAc ß 1,4-galactosyltransferase, polypeptide 1 (B4GALT1) was significantly down-regulated upon ZFX silencing, which is implicated in the response of K562 cells to the treatment of imatinib mesylate (IM). In addition, lectin blot assay showed that the galactosylation of glycoproteins in K562 cells was suppressed upon ZFX silencing. Interestingly, overexpression of B4GALT1 restored the growth and conferred drug resistance to ZFX-silenced cells. Taken together, we have demonstrated that ZFX is aberrantly expressed in multiple human leukemic cells and it modulates the growth and drug response of leukemic cells partially via B4GALT1, which suggests that ZFX is a new regulator of leukemic cells and warrants intensive investigations on this 'stemness' regulator in these deadly diseases.

Marine bacterial chemoresponse to a stepwise chemoattractant stimulus.

We found recently that polar flagellated marine bacterium Vibrio alginolyticus is capable of exhibiting taxis toward a chemical source in both forward and backward swimming directions. How the microorganism coordinates these two swimming intervals, however, is not known. The work presented herein is aimed at determining the response functions of the bacterium by applying a stepwise chemoattractant stimulus while it is swimming forward or backward. The important finding of our experiment is that the bacterium responds to an identical chemical signal similarly during the two swimming intervals. For weak stimuli, the difference is mainly in the amplitudes of the response functions while the reaction and adaptation times remain unchanged. In this linear-response regime, the amplitude in the forward swimming interval is approximately a factor of two greater than in the backward direction. Our observation suggests that the cell processes chemical signals identically in both swimming intervals, but the responses of the flagellar motor to the output of the chemotaxis network, the regulator CheY-P concentration, are different. The biological significance of this asymmetrical response in polar flagellated marine bacteria is discussed.

A Non-Poissonian Flagellar Motor Switch Increases Bacterial Chemotactic Potential.

We investigate bacterial chemotactic strategies using run-tumble and run-reverse-flick motility patterns. The former is typically observed in enteric bacteria such as Escherichia coli and Salmonella and the latter was recently observed in the marine bacteria Vibrio alginolyticus and is possibly exhibited by other polar flagellated species. It is shown that although the three-step motility pattern helps the bacterium to localize near hot spots, an exploitative behavior, its exploratory potential in short times can be significantly enhanced by employing a non-Poissonian regulation scheme for its flagellar motor switches.

Fast-moving bacteria self-organize into active two-dimensional crystals of rotating cells.

We investigate a new form of collective dynamics displayed by Thiovulum majus, one of the fastest-swimming bacteria known. Cells spontaneously organize on a surface into a visually striking two-dimensional hexagonal lattice of rotating cells. As each constituent cell rotates its flagella, it creates a tornadolike flow that pulls neighboring cells towards and around it. As cells rotate against their neighbors, they exert forces on one another, causing the crystal to rotate and cells to reorganize. We show how these dynamics arise from hydrodynamic and steric interactions between cells. We derive the equations of motion for a crystal, show that this model explains several aspects of the observed dynamics, and discuss the stability of these active crystals.

Bacterial motility patterns reveal importance of exploitation over exploration in marine microhabitats. Part I: theory.

Bacteria use different motility patterns to navigate and explore natural habitats. However, how these motility patterns are selected, and what their benefits may be, are not understood. In this article, we analyze the effect of motility patterns on a cell's ability to migrate in a chemical gradient and to localize at the top of the gradient, the two most important characteristics of bacterial chemotaxis. We will focus on two motility patterns, run-tumble and run-reverse-flick, that are observed and characterized in enteric bacterium Escherichia coli and marine bacterium Vibrio alginolyticus, respectively. To make an objective comparison, master equations are developed on the basis of microscopic motions of the bacteria. An unexpected yet significant result is that by adopting the run-reverse-flick motility pattern, a bacterium can reduce its diffusivity without compromising its drift in the chemical gradient. This finding is biologically important as it suggests that the motility pattern can improve a microorganism's ability to sequester nutrients in a competitive environment.

From the Cover: Bacterial flagellum as a propeller and as a rudder for efficient chemotaxis.

We investigate swimming and chemotactic behaviors of the polarly flagellated marine bacteria Vibrio alginolyticus in an aqueous medium. Our observations show that V. alginolyticus execute a cyclic, three-step (forward, reverse, and flick) swimming pattern that is distinctively different from the run-tumble pattern adopted by Escherichia coli. Specifically, the bacterium backtracks its forward swimming path when the motor reverses. However, upon resuming forward swimming, the flagellum flicks and a new swimming direction is selected at random. In a chemically homogeneous medium (no attractant or repellent), the consecutive forward t(f) and backward t(b) swimming times are uncorrelated. Interestingly, although t(f) and t(b) are not distributed in a Poissonian fashion, their difference Δt = |t(f) - t(b)| is. Near a point source of attractant, on the other hand, t(f) and t(b) are found to be strongly correlated, and Δt obeys a bimodal distribution. These observations indicate that V. alginolyticus exploit the time-reversal symmetry of forward and backward swimming by using the time difference to regulate their chemotactic behavior. By adopting the three-step cycle, cells of V. alginolyticus are able to quickly respond to a chemical gradient as well as to localize near a point source of attractant.

Clinical outcome of autologous hematopoietic stem cell infusion via hepatic artery or portal vein in patients with end-stage liver diseases.

OBJECTIVE: To investigate the efficacy of hematopoietic stem cell (HSC) transplantation via the hepatic artery vs. the portal vein for end-stage liver disease (ESLD). METHODS: Patients with hepatic decompensation were prospectively recruited from September 2010 to September 2012 to receive HSC transplantation via the hepatic artery or the portal vein. Liver function was examined at 3, 6, and 12 months after transplantation. Liver biopsy Results were analyzed using the Knodell score. RESULTS: Eighty patients (58 males and 22 females) were enrolled in the study. The Child-Pugh score was grade B in 69 cases, and grade C in the remaining 11 cases. HSC transplantation was performed via the portal vein in 36 patients and via the hepatic artery in 44 patients. ALT levels decreased while serum albumin levels increased significantly in both groups at 6 and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Total bilirubin levels decreased significantly in both groups at 3, 6, and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Additionally, prothrombin time decreased in both groups at 12 months after HSC transplantation (P<0.05 compared with pre-transplantation level). There were no significant differences in ALT, total bilirubin and prothrombin time between the two groups either before or after transplantation. Moreover, Knodell score decreased significantly at 6 and 12 months. Histological examination showed that liver cell edema, degeneration, necrosis, and inflammation were significantly relieved at 3, 6, and 12 months after transplantation. The incidence of portal vein thrombosis, upper gastrointestinal bleeding, and hepatic encephalopathy were 1.25%, 3.75%, and 2.5% respectively. The one-year survival rate was 100%. CONCLUSIONS: Autologous HSC transplantation improves liver function and histology in ESLD patients. The administration route of HSC has no significant impact on the efficacy of transplantation.

[Xiaojiang River Basin Ecological Environmental Quality Spatiotemporal Pattern and Evolutionary Trend Analysis Using GEE from 1990 to 2022].

Assessment and monitoring of the quality of the ecological environment in the area is a very important fundamental task in the development of ecological civilization in the Xiaojiang River Basin in Yunnan Province, which serves as a demonstration area for ecological restoration in the upper reaches of the Yangtze River. The Landsat remote sensing images from 1990, 1995, 2000, 2005, 2010, 2014, 2018, and 2022 were chosen, and the four indexes of greenness （NDMVI）, humidity （WET）, dryness （NDBSI）, and heat （LST） were extracted. The remote sensing ecological index （RSEI） was created using the principal component analysis method, then the spatial and temporal patterns and trends of ecological quality in the Xiaojiang River Basin between 1990 and 2022 were examined using the GEE platform, ArcGIS 10.7 platform, and Python platform, combining the analysis methods of geographic information mapping, coefficient of variation, Mann-Kendall trend test, Sen's slope estimation, and Hurst's index. The findings demonstrated that： ① the ecological quality of the study area had more obvious geographic differentiation spatially, and by 2022, the areas with excellent and good ecological quality grades were primarily distributed in the areas with better alpine vegetation cover, and those with poor ecological quality were primarily distributed in the areas of the mudslide ravines with relatively low terrain. On a time scale, the study area's RSEI index increased from 0.41 in 1990 to 0.55 in 2022, with a fluctuating overall trend of ecological quality improvement and an average increase of 0.048（10 a） -1； this progress was directly related to a number of ecological construction initiatives that have been energetically carried out, such as converting farms to forests, preventing mudslides, saving soil and water, managing heavy metal contamination, etc. ② The RSEI was more appropriate for the evaluation of ecological quality in alpine ravine areas because, in comparison to the NDVI index, the NDVMI adopted in this study was more sensitive to vegetation information in topographic undulation areas, especially in shaded areas, and could more accurately and quantitatively describe the vegetation information. ③ The RSEI in the Xiaojiang River Basin had a mean coefficient of variation of 0.202. Overall, its volatility was low, and its high volatility was mostly concentrated in the mudslide gully area along both sides of the Xiaojiang River fracture zone, where the surface was made up of bare rocks and sediment that was easily impacted by the changing of the seasons, the climate, and human activity. ④ The quality of the ecological environment in the region was significantly improving, with the rising area reaching 85.72% of the total area and the declining area accounting for approximately 10.15% of the total area. The future trend of change will be dominated by ongoing improvement and future degradation, accounting for 44.75% and 39.97%, respectively. It is important to pay close attention to areas that could potentially degrade. The findings of this study can serve as a theoretical foundation for additional ecological environmental conservation, management, and sustainable development in the Xiaojiang River Basin.

Myeloid-derived suppressor cells promote the formation of abdominal aortic aneurysms through the IL-3-ICOSL-ICOS axis.

Th17 cells are powerful inflammation promoters in the pathogenesis of abdominal aortic aneurysms (AAAs). Myeloid-derived suppressor cells (MDSCs) can promote the differentiation of Th17 cells in chronic inflammatory autoimmune injury. Here, we aim to examine whether MDSCs regulate the differentiation of Th17 cells to participate in the development of AAA. We demonstrated an abnormal accumulation of MDSCs in AAA patients, which was positively associated with Th17 cells. We established angiotensin II-induced apolipoprotein E knockout mice and found the impaired immunosuppressive function of M-MDSCs. After systemic injection of anti-Gr-1 antibody in AAA mice to deplete circulating MDSCs, AAA formation and the differentiation of Th17 cells were abolished, and the overexpression of inducible T-cell costimulator (ICOS) on Th17 cells was reversed accordingly. Regulating the expression of ICOS ligand (ICOSL) on MDSCs affects the differentiation of Th17 cells. The adoptive transfer of ICOSLlowMDSCs in AAA mice inhibited the differentiation of Th17 cells and the development of AAA. Meanwhile, rIL-3 promoted the survival and immunosuppressive dysfunction of MDSCs, upregulated ICOSL expression on MDSCs by inhibiting activation of the PI3K/AKT signaling pathway, and regulated MDSCs to promote the differentiation of Th17 cells via the ICOSL-ICOS axis. An increase in serum IL-3, ICOSL+MDSCs, and ICOS+Th17 cells was detected in AAA patients, and IL-3 levels were positively correlated with the proportion of ICOSL+MDSC cells. In conclusion, we uncovered a pivotal role of MDSCs in promoting the differentiation of Th17 cells through the IL-3-ICOSL-ICOS axis during AAA, providing an important theoretical basis for understanding the pathogenesis of AAA.

Ultra-processed food intake and risk of depression: a systematic review.

Introduction: Objective: to conduct a systematic review of the observational studies analyzing the association between ultra-processed food (UPF) intake and the risk of depression. Design: the search adhered to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); a search for observational studies published until June 2020 was performed in PubMed, Embase, Cochrane Library, and Web of Science databases, followed by additional manual searches. Eight reviewers, working independently in teams of two, screened studies for eligibility, extracted data, and assessed risk of bias. We resolved disagreements through discussion or, if necessary, through adjudication by a third (LH). And the study assessed cross-sectional studies using the Agency for Healthcare Research and Quality (AHRQ) methodological checklist and cohort and case-control studies using the Newcastle-Ottawa Scale (NOS) for quality. We used a tabular format to summarize the articles. Results: twenty-eight studies evaluating UPF intake and risk of depression were finally selected, 21 of which had a cross-sectional design, 6 studies had a cohort design, and 1 had a case-control design. Of these, 4 cohort studies and 17 cross-sectional studies found that consumption of UPF were positively associated with depression or depressive symptoms. Conclusions: our review demonstrated that most studies included in the systematic review showed that UPF consumption is associated with the risk of depression. Future studies should consider the use of validated food intake assessments and standardized depression assessment methods to promote comparability between studies.

Introducción: Objetivo: realizar una revisión sistemática de los estudios observacionales que analizan la asociación entre la ingesta de alimentos ultraprocesados (UPF) y el riesgo de depresión. Diseño: la búsqueda se adhirió a las directrices Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); se realizó una búsqueda de estudios observacionales publicados hasta junio de 2020 en las bases de datos PubMed, Embase, Cochrane Library y Web of Science, seguida de búsquedas manuales adicionales. Ocho revisores, que trabajaron de forma independiente en equipos de dos, seleccionaron los estudios para su elegibilidad, extrajeron los datos y evaluaron el riesgo de sesgo. Los desacuerdos se resolvieron a través de la discusión o, si era necesario, a través de la adjudicación de un tercero. Se evaluaron los estudios transversales mediante la lista de comprobación metodológica de la Agency for Healthcare Research and Quality (AHRQ) y los estudios de cohortes y de casos y controles mediante la escala Newcastle-Ottawa (NOS) para la calidad. Se utilizó un formato tabular para resumir los artículos. Resultados: finalmente se seleccionaron 28 estudios que evaluaban la ingesta de UPF y el riesgo de depresión, 21 de los cuales tenían un diseño transversal, 6 un diseño de cohortes y 1 un diseño de casos y controles. De ellos, 4 estudios de cohortes y 17 estudios transversales encontraron que el consumo de UPF se asociaba positivamente con la depresión o los síntomas depresivos. Conclusiones: nuestra revisión demostró que la mayoría de los estudios incluidos en la revisión sistemática mostraron que el consumo de UPF está asociado con el riesgo de depresión. Los estudios futuros deberían considerar el uso de evaluaciones validadas del consumo de alimentos y métodos estandarizados de evaluación de la depresión para promover la comparabilidad entre los estudios.