ECM concentration and cell-mediated traction forces play a role in vascular network assembly in 3D bioprinted tissue

Tissue vascularization is critical to enable oxygen and nutrient supply. Therefore, establishing expedient vasculature is necessary for the survival of tissue after transplantation. The use of biomechanical forces, such as cell-induced traction forces, may be a promising method to encourage growth of the vascular network. Three-dimensional (3D) bioprinting, which offers unprecedented versatility through precise control over spatial distribution and structure of tissue constructs, can be used to generate capillary-like structures in vitro that would mimic microvessels. This study aimed to develop an in vitro, 3D bioprinted tissue model to study the effect of cellular forces on the spatial organization of vascular structures and tissue maturation. The developed in vitro model consists of a 3D bioprinted polycaprolactone (PCL) frame with a gelatin spacer hydrogel layer and a gelatin–fibrin–hyaluronic acid hydrogel layer containing normal human dermal fibroblasts and human umbilical vein endothelial cells printed as vessel lines on top. The formation of vessel-like networks and vessel lumens in the 3D bioprinted in vitro model was assessed at different fibrinogen concentrations with and without inhibitors of cell-mediated traction forces. Constructs containing 5 mg/ml fibrinogen had longer vessels compared to the other concentrations of fibrinogen used. Also, for all concentrations of fibrinogen used, most of the vessel-like structures grew parallel to the direction the PCL frame-mediated tensile forces, with very few branching structures observed. Treatment of the 3D bioprinted constructs with traction inhibitors resulted in a significant reduction in length of vessel-like networks. The 3D bioprinted constructs also had better lumen formation, increased collagen deposition, more elaborate actin networks, and well-aligned matrix fibers due to the increased cell-mediated traction forces present compared to the non-anchored, floating control constructs. This study showed that cell traction forces from the actomyosin complex are critical for vascular network assembly in 3D bioprinted tissue. Strategies involving the use of cell-mediated traction forces may be promising for the development of bioprinting approaches for fabrication of vascularized tissue constructs.     

子痫前期患者肠道微生物特征及益生菌调节

子痫前期(preeclampsia,PE)是妊娠期高血压疾病(hypertensive disorders of pregnancy,HDP)之一,严重损害母婴健康,影响3%～5%的妊娠。随高通量测序技术的发展和普及,肠道微生物与人类健康和疾病的关系逐渐清晰。PE患者肠道微生物群结构变化与疾病的发生发展密切相关,失调的肠道菌群很可能会成为PE早期诊断的生物标志物或干预的靶点。本文总结了以测序技术为基础获得的正常妊娠女性和PE患者肠道微生物分布规律数据,并提出益生菌调理建议,以期为PE的科学预测、精准干预提供理论支持。     

肠内营养对乳腺癌术后化疗患者肠道菌群及生活质量的影响

目的研究肠内营养对乳腺癌术后化疗患者肠道菌群、生活质量、营养指标水平的影响。方法选取2012年7月至2018年1月于我院进行乳腺癌术后化疗的91例女性乳腺癌患者为研究对象,根据是否进行肠内营养将患者分为肠内营养组和对照组,观察化疗前后2组患者肠道菌群、生活质量、营养指标水平的变化及不良反应发生情况。结果治疗前2组患者肠道菌群、生活质量、营养指标水平差异无统计学意义(均P0.05)。治疗后,肠内营养组患者肠道双歧杆菌数量为(6.7±0.5)lg CFU/g、乳杆菌数量为(8.5±0.4)lg CFU/g,均显著高于治疗前,同时显著高于对照组(均P0.05)。治疗后肠内营养组患者出现反酸、腹胀、便秘等胃肠道不良反应的比例与对照组比较差异无统计学意义(均P0.05)。治疗后两组患者总体健康、认知功能、情绪功能、角色功能、社会功能、活力、躯体疼痛、躯体功能评分显著高于治疗前(均P0.05),且肠内营养组患者生活质量各指标的评分显著高于对照组(均P0.05)。治疗后肠内营养组患者血清总蛋白(TB)、血清清蛋白(ALB)、血清前清蛋白(PA)、转铁蛋白(TF)水平均显著高于对照组(均P0.05)。结论肠内营养可预防乳腺癌术后化疗患者肠道菌群的紊乱及营养不良的发生,安全有效,有助于提高乳腺癌患者的生活质量。     

Anti‐interleukin‐5‐neutralizing antibody attenuates caradiac injury and cadiac dysfunction by aggravating the inflammatory response in doxorubicin‐treated mice

Previous studies have demonstrated that interleukins (ILs) are closely associated with doxorubicin (DOX)‐induced cardiac injury. IL‐5 is an important member of the IL family, and this study was performed to investigate whether IL‐5 affects DOX‐induced cardiac injury and its underlying mechanisms. The cardiac IL‐5 expression was first detected and the results showed that cardiac IL‐5 levels were significantly lower in DOX‐treated mice, and IL‐5 was mainly derived from cardiac macrophage (Mø). In addition, some DOX‐treated mice received an injection of anti‐IL‐5‐neutralizing antibody (nAb), and we found that treatment with a mouse anti‐IL‐5 nAb significantly upregulated the levels of myocardial injury markers, aggravated cardiac dysfunction, increased M1 macrophage (Mø1) and decreased M2 macrophage (Mø2) differentiation, and promoted apoptotic marker expression. Furthermore, the effect of mouse IL‐5 nAb on DOX‐induced Mø differentiation and its role on mouse cardiomyocyte (MCM) cells apoptosis were detected in vitro, and the results exhibited that mouse IL‐5 nAb promoted Mø1 differentiation but inhibited Mø2 differentiation in vitro and alleviated apoptosis in MCM cells. Our results found a mouse anti‐IL‐5 nAb‐aggravated DOX‐induced cardiac injury and dysfunction by alleviating the inflammatory response and myocardial cell apoptosis.     

Melatonin ameliorates renal fibroblast-myofibroblast transdifferentiation and renal fibrosis through miR-21-5p regulation

Fibroblast-myofibroblast transdifferentiation (FMT) is widely recognized as the major pathological feature of renal fibrosis. Although melatonin has exerted antifibrogenic activity in many diseases, its role in renal FMT remains unclear. In the present study, the aim was to explore the effect of melatonin on renal FMT and the underlying mechanisms. We established the transforming growth factor (TGF)-β1 stimulated rat renal fibroblast cells (NRK-49F) model in vitro and unilateral ureteral obstruction (UUO) mice model in vivo. We assessed levels of α-smooth muscle actin (α-SMA), col1a1 and fibronectin, STAT3 and AP-1, as well as miR-21-5p and its target genes (Spry1, PTEN, Smurf2 and PDCD4). We found that melatonin reduced the expression of α-SMA, col1a1 and fibronectin, as well as the formation of α-SMA filament in TGF-β1-treated NRK-49F cells. Meanwhile, melatonin inhibited STAT3 phosphorylation, down-regulated miR-21-5p expression, and up-regulated Spry1 and PTEN expression. Moreover, miR-21-5p mimics partially antagonized the anti-fibrotic effect of melatonin. For animal experiments, the results revealed that melatonin remarkably ameliorated UUO-induced renal fibrosis, attenuated the expression of miR-21-5p and pro-fibrotic proteins and elevated Spry1 and PTEN expression. Nevertheless, agomir of miR-21-5p blocked the renoprotective effect of melatonin in UUO mice. These results indicated that melatonin could alleviate TGF-β1-induced renal FMT and UUO-induced renal fibrosis through down-regulation of miR-21-5p. Regulation of miR-21-5p/PTEN and/or miR-21-5p/Spry1 signal might be involved in the anti-fibrotic effect of melatonin in the kidneys of UUO mice.     

Silicon Anode with High Initial Coulombic Efficiency by Modulated Trifunctional Binder for High‐Areal‐Capacity Lithium‐Ion Batteries

High‐capacity electrode materials play a vital role for high‐energy‐density lithium‐ion batteries. Silicon (Si) has been regarded as a promising anode material because of its outstanding theoretical capacity, but it suffers from an inherent volume expansion problem. Binders have demonstrated improvements in the electrochemical performance of Si anodes. Achieving ultrahigh‐areal‐capacity Si anodes with rational binder strategies remains a significant challenge. Herein, a binder‐lithiated strategy is proposed for ultrahigh‐areal‐capacity Si anodes. A hard/soft modulated trifunctional network binder (N‐P‐LiPN) is constructed by the partially lithiated hard polyacrylic acid as a framework and partially lithiated soft Nafion as a buffer via the hydrogen binding effect. N‐P‐LiPN has strong adhesion and mechanical properties to accommodate huge volume change of the Si anode. In addition, lithium‐ions are transferred via the lithiated groups of N‐P‐LiPN, which significantly enhances the ionic conductivity of the Si anode. Hence, the Si@N‐P‐LiPN electrodes achieve the highest initial Coulombic efficiency of 93.18% and a stable cycling performance for 500 cycles at 0.2 C. Specially, Si@N‐P‐LiPN electrodes demonstrate an ultrahigh‐areal‐capacity of 49.59 mAh cm^?2. This work offers a new approach for inspiring the battery community to explore novel binders for next‐generation high‐energy‐density storage devices.     

Constructing High‐Performance Organic Photovoltaics via Emerging Non‐Fullerene Acceptors and Tandem‐Junction Structure

In consideration of the unique advantages of new non‐fullerene acceptors and the tandem‐junction structure, organic photovoltaics (OPVs) based on them are very promising. Studies related to this emerging area began in 2016 with achieved power conversion efficiencies (PCEs) of 8–10%, which have now been boosted to 17%. In this essay, the construction of high‐performance OPVs is discussed, with a focus on combining the advantages of new non‐fullerene acceptors and the tandem‐junction structure. In order to achieve higher PCEs, methods to enable high short‐circuit current density, open‐circuit voltage, and fill factor are discussed. In addition, the stability and reproducibility of high‐efficiency OPVs are also addressed. Herein, it is forecast that the new non‐fullerene acceptors‐based tandem‐junction OPVs will become the next big wave in the field and achieve high PCEs over 20% in the near future. Some promising research directions on this emerging hot topic are proposed which may further push the field into the 25% high efficiency era and considerably advance the technology beyond laboratory research.     

Light Harvesting at Oblique Incidence Decoupled from Transmission in Organic Solar Cells Exhibiting 9.8% Efficiency and 50% Visible Light Transparency

For many years, it has been recognized that potential organic photovoltaic cells must be integrated into elements requiring high transparency. In most of such elements, sunlight is likely to be incident at large angles. Here it is demonstrated that light transmission can be largely decoupled from harvesting by optically tailoring an infrared shifted nonfullerene acceptor based organic cell architecture. A 9.67% power conversion efficiency at 50° incidence is achieved together with an average visual transmission above 50% at normal incidence. The deconstruction of a 1D nanophotonic structure is implemented to conclude that just two λ/4 thick layers are essential to reach, for a wide incidence angle range, a higher than 50% efficiency increase relative to the standard configuration reference. In an outdoor measurement of vertically positioned 50% visible transparent cells, it is demonstrated that 9.80% of sunlight energy can be converted into electricity during the course of 1 day.     

Sarcoplasmic Phospholamban Protein Is Involved in the Mechanisms of Postresuscitation Myocardial Dysfunction and the Cardioprotective Effect of Nitrite during Resuscitation

Objectives

Sarcoplasmic reticulum (SR) Ca²⁺-handling proteins play an important role in myocardial dysfunction after acute ischemia/reperfusion injury. We hypothesized that nitrite would improve postresuscitation myocardial dysfunction by increasing nitric oxide (NO) generation and that the mechanism of this protection is related to the modulation of SR Ca²⁺-handling proteins.

Methods

We conducted a randomized prospective animal study using male Sprague-Dawley rats. Cardiac arrest was induced by intravenous bolus of potassium chloride (40 µg/g). Nitrite (1.2 nmol/g) or placebo was administered when chest compression was started. No cardiac arrest was induced in the sham group. Hemodynamic parameters were monitored invasively for 90 minutes after the return of spontaneous circulation (ROSC). Echocardiogram was performed to evaluate cardiac function. Myocardial samples were harvested 5 minutes and 1 hour after ROSC.

Results

Myocardial function was significantly impaired in the nitrite and placebo groups after resuscitation, whereas cardiac function (i.e., ejection fraction and fractional shortening) was significantly greater in the nitrite group than in the placebo group. Nitrite administration increased the level of nitric oxide in the myocardium 5 min after resuscitation compared to the other two groups. The levels of phosphorylated phospholamban (PLB) were decreased after resuscitation, and nitrite increased the phosphorylation of phospholamban compared to the placebo. No significant differences were found in the expression of sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2a) and ryanodine receptors (RyRs).

Conclusions

postresuscitation myocardial dysfunction is associated with the impairment of PLB phosphorylation. Nitrite administered during resuscitation improves postresuscitation myocardial dysfunction by preserving phosphorylated PLB protein during resuscitation.