Light‐emitting diodes (LEDs) with directional and polarized light emission have many photonic applications, and beam shaping of these devices is fundamentally challenging because they are Lambertian ...light sources. In this work, using organic and perovskite LEDs (PeLEDs) for demonstrations, by selectively diffracting the transverse electric (TE) waveguide mode while suppressing other optical modes in a nanostructured LED, the authors first demonstrate highly directional light emission from a full‐area organic LED with a small divergence angle less than 3° and a TE to transverse magnetic (TM) polarization extinction ratio of 13. The highly selective diffraction of only the TE waveguide mode is possible due to the planarization of the device stack by thermal evaporation and solution processing. Using this strategy, directional and polarized emission from a perovskite LED having a current efficiency 2.6 times compared to the reference planar device is further demonstrated. This large enhancement in efficiency in the PeLED is attributed to a larger contribution from the TE waveguide mode resulting from the high refractive index in perovskite materials.
Highly directional and polarized light emission is demonstrated in thin‐film light‐emitting diodes (LEDs) by suppressing the background emission and extracting only the transverse electric (TE) waveguide mode. It is found that the TE waveguide mode increases with the refractive index of the emitting layer and a 2.6 times higher current efficiency is achieved in a perovskite LED.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Autophagy is a catabolic lysosomal degradation process essential for cellular homeostasis and cell survival. Dysfunctional autophagy has been associated with a wide range of human diseases, e.g., ...cancer and neurodegenerative diseases. A large number of small molecules that modulate autophagy have been widely used to dissect this process and some of them, e.g., chloroquine (CQ), might be ultimately applied to treat a variety of autophagy-associated human diseases. Here we found that vacuolin-1 potently and reversibly inhibited the fusion between autophagosomes and lysosomes in mammalian cells, thereby inducing the accumulation of autophagosomes. Interestingly, vacuolin-1 was less toxic but at least 10-fold more potent in inhibiting autophagy compared with CQ. Vacuolin-1 treatment also blocked the fusion between endosomes and lysosomes, resulting in a defect in general endosomal-lysosomal degradation. Treatment of cells with vacuolin-1 alkalinized lysosomal pH and decreased lysosomal Ca
2+
content. Besides marginally inhibiting vacuolar ATPase activity, vacuolin-1 treatment markedly activated RAB5A GTPase activity. Expression of a dominant negative mutant of RAB5A or RAB5A knockdown significantly inhibited vacuolin-1-induced autophagosome-lysosome fusion blockage, whereas expression of a constitutive active form of RAB5A suppressed autophagosome-lysosome fusion. These data suggest that vacuolin-1 activates RAB5A to block autophagosome-lysosome fusion. Vacuolin-1 and its analogs present a novel class of drug that can potently and reversibly modulate autophagy.
Full text
Available for:
BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Medical image segmentation is one of the important steps in the computer-aided diagnosis of pancreas diseases. Although some models have been proposed to deal with the task of automatic pancreas ...segmentation, it is still challenging due to the small size, variable shape and unclear boundary of pancreas. In this paper, we propose a target-aware U-Net (tU-Net) using fuzzy skip connection for pancreas segmentation. Through adding a fuzzy skip connection module into the U-Net architecture, the low-level features can be transformed into the high-level semantic features, which facilitates the segmentation of small and changeable targets of pancreas. Based on the fuzzy feature mapping, we also design a target attention mechanism consists of global average pooling and depthwise convolution. It makes the decoder of the network more sensitive to target features by increasing weights of important channels. The proposed method is evaluated on the NIH dataset of 82 CT volumes, and the pancreas Medical Segmentation Decathlon (MSD) challenge dataset of 281 CT volumes. The proposed model achieves better results comparing with other state-of-the-art models.
•Propose a target-aware U-Net for refined pancreas segmentation.•Design the fuzzy skip connection to obtain high-level semantics from the feature map.•Add target attention mechanism through combining global average pooling and depthwise convolution operations.•Experimental results on pancreas CT volumes validate the effectiveness of the proposed method.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Piezo1, the mechanosensory ion channel, has attracted increasing attention for its essential roles in various inflammatory responses and immune-related diseases. Although most of the key immune cells ...in inflammatory bowel disease (IBD) have been reported to be regulated by Piezo1, the specific role of Piezo1 in colitis has yet to be intensively studied. The present study investigated the impact of pharmacological inhibition of Piezo1 on dextran sulfate sodium (DSS)-induced colitis and explored the role of Piezo1 in intestinal immune cells in the context of colitis. We observed upregulated expression of Piezo1 in the colon tissue of mice with DSS-induced colitis. Pharmacological inhibition of Piezo1 by GsMTx4 diminished the severity of colitis. Piezo1 inhibition downregulated the expression of pro-inflammatory mediators Il1b, Il6, and Ptgs2 in colonic tissue and suppressed the production of IL-6 from macrophages and dendritic cells without altering the balance of T helper (Th) cells. In particular, Piezo1 did not affect cell viability but regulated cell proliferation and production of IL-17A in group 3 innate lymphoid cells (ILC3s), which is dependent on the PI3K-Akt-mTOR signaling pathway. Our findings uncover Piezo1 as an effective regulator of gut inflammation. Targeting Piezo1 could be a promising strategy to modulate intestinal immunity in IBD.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
With the extensive use of antibiotics, resulting in increasingly serious problems of bacterial resistance, antimicrobial therapy has become a global concern. Metal-organic frameworks (MOFs) are ...low-density porous coordination materials composed of metal ions and organic ligands, which can form composite materials with biomacromolecules such as proteins and polysaccharides. In recent years, MOFs and their derivatives have been widely used in the antibacterial field as efficient antibacterial agents. This review offers a detailed summary of the antibacterial applications of MOFs and their composites, and the different synthesis methods and antibacterial mechanisms of MOFs and MOF-based composites are briefly introduced. Finally, the challenges and prospects of MOFs-based antibacterial materials in the rapidly developing medical field were briefly discussed. We hope this review will provide new strategies for the medical application of MOFs-based antibacterial materials.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Display omitted
•High levels of reactive oxygen species (ROS) were found in tendinopathy.•MSNs-PC promote tenogenesis differentiation of TSPCs.•MSNs-PC alleviated heterotopic tendon ossification by ...scavenging excess ROS.
In the inflammatory environment of tendinopathy, tendon stem/progenitor cells (TSPCs) have been demonstrated to aberrantly differentiate into osteochondral lineage causing late-stage heterotopic ossification (HO) of the tendon, which severely damages tissue function and worsens patients’ activities. However, no effective treatment for tendinopathy currently exist because the mechanism underlying the TSPCs abnormal differentiation is unclear. In this article, high levels of reactive oxygen species (ROS) were found in tendinopathy samples. In vitro results revealed that proanthocyanidins (PC) can potentially regulate the differentiation of TSPCs by scavenging excess ROS, which would promote tenogenesis instead of chondrogenesis or osteogenesis. Moreover, in vivo results demonstrated that PC-loaded mesoporous silica nanocomposite (MSNs-PC) hinders the recurrence of HO in repaired tendons owing to the inhibition of oxidative stress, showing anti-inflammatory effects. Our findings indicate a high level of ROS in tendinopathy, which is probably the cause of aberrant differentiation of TSPCs. MSNs-PCs can effectively ameliorate HO of the tendon by scavenging excess ROS, providing a promising avenue to for other ROS-related diseases.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Gene expression has been widely used in functional genomics research; however, the gene expressions quantified with different methods have been frequently inconsistent, thus challenging the ...conclusions from such research. Here we have addressed this issue, while taking into account RNA alternative splicing. We found that when a gene was subjected to RNA alternative splicing, it was impossible or difficult to properly quantify the expression of a transcript of the gene or its overall expression using quantitative real-time PCR (qPCR), Northern hybridization, microarray, or serial analysis of gene expression. Shot-gun RNA-seq was the most proper to quantify the expression of a transcript or a gene in such cases. Moreover, the expressions of individual transcripts quantified by shot-gun RNA-seq were highly reproducible (r = 0.90–0.98) between individuals. Therefore, shot-gun or full-length RNA-seq should be the method of choice to properly quantify the expression of a transcript or a gene.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Circulating histones negatively correlate with monocyte levels in septic patients.•Histones induce apoptosis and defective bacterial phagocytosis in macrophages.•Low Mg2+ levels are linked to low ...monocyte levels in septic patients.•Mg2+ attenuates histone-induced macrophage damage by regulating the calcium signal.•Mg2+ may be a promising treatment for septic patients with raised circulating histones.
Extracellular histones have been determined as important mediators of sepsis, which induce excessive inflammatory responses in macrophages and impair innate immunity. Magnesium (Mg2+), one of the essential nutrients of the human body, contributes to the proper regulation of immune function. However, no reports indicate whether extracellular histones affect survival and bacterial phagocytosis in macrophages and whether Mg2+ is protective against histone-induced macrophage damage. Our clinical data revealed a negative correlation between circulating histone and monocyte levels in septic patients, and in vitro experiments confirmed that histones induced mitochondria-associated apoptosis and defective bacterial phagocytosis in macrophages. Interestingly, our clinical data also indicated an association between lower serum Mg2+ levels and reduced monocyte levels in septic patients. Moreover, in vitro experiments demonstrated that Mg2+ attenuated histone-induced apoptosis and defective bacterial phagocytosis in macrophages through the PLC/IP3R/STIM-mediated calcium signaling pathway. Importantly, further animal experiments proved that Mg2+ significantly improved survival and attenuated histone-mediated lung injury and macrophage damage in histone-stimulated mice. Additionally, in a cecal ligation and puncture (CLP) + histone-induced injury mouse model, Mg2+ inhibited histone-mediated apoptosis and defective phagocytosis in macrophages and further reduced bacterial load. Overall, these results suggest that Mg2+ supplementation may be a promising treatment for extracellular histone-mediated macrophage damage in sepsis.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was ...designed to assess the efficacy and safety of granisetron in patients with sepsis.
Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome.
The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49-1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups.
Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration.
Vitamin D deficiency is common in critically ill patients with suspected infection and is strongly associated with the predisposition of sepsis and a poor prognosis. The effectiveness of vitamin D ...supplementation for preventing sepsis remains unclear. This retrospective cohort study investigated the effect of vitamin D supplementation on sepsis prophylaxis in critically ill patients with suspected infection.
This retrospective cohort study included 19,816 adult patients with suspected infection in intensive care units (ICU) from 2008 to 2019 at the Beth Israel Deaconess Medical Center, Boston, USA. The included patients were divided into the vitamin D cohort or non-vitamin D cohort according to vitamin D administration status. The primary outcomes were the incidence of sepsis in ICU. The secondary outcomes included 28-day all-cause mortality, length of ICU and hospital stay and the requirements of vasopressors or mechanical ventilation. A propensity score matching cohort was used to test the differences in primary and secondary outcomes between groups.
The results showed that vitamin D supplementation demonstrated a lower risk of sepsis (odd ratio 0.46; 95% CI 0.35-0.60;
< 0.001) and a lower risk of new mechanical ventilation requirement (odd ratio 0.70; 95% CI 0.53-0.92;
= 0.01), but no significant difference in the risk of 28-day mortality was observed (hazard ratio 1.02; 95% CI 0.77-1.35;
= 0.89). In the sensitive analysis, among the patients who suspected infection within 24 h before or after ICU admission, a lower risk of sepsis and a lower percentage of new mechanical ventilation also were detected in the vitamin D cohort.
Vitamin D supplementation may have a positively prophylactic effect on sepsis in critically ill patients with suspected infection.
PDF
