The dynamic cell–cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are ...extracellular vesicles that actively participate in cell–cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the β‐catenin/Tcf‐4‐activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA‐146a‐5p (miR‐146a) is the major miRNA in CRCSC exosomes and exosomal miR‐146a promotes stem‐like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR‐146a expression in serum exhibits higher miR‐146aHigh/NumbLow CRCSC traits, an increased number of tumor‐filtrating CD66(+) neutrophils and a decreased number of tumor‐infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome‐mediated stemness expansion.
What's new?
The tumor microenvironment (TME) is composed of heterogeneous tumor cells and host cells interacting with each other to promote disease progression. However, diagnostic and prognostic biomarkers to monitor the cancer stem cells (CSCs)‐host interplay are lacking. Here, the authors explore the role of tumor exosomes in cancer stemness and demonstrate that RAB27B‐assisted secretion of miRNA‐dominant exosomes is one critical feature of CSCs. Importantly, they show that colorectal cancer stem cells release miR‐146a‐loaded oncogenic exosomes for reprogramming non‐CSC cells and demonstrate the clinical relevance of exosomal miR‐146a in predicting the TME of CRC patients.
In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study.
Subjects admitted ...to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020.
There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70).
Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.
Objective
Open tibial fractures are frequently encountered in high‐energy traumas and can result in significant complications such as nonunion, osteomyelitis, and even amputation. Among open tibial ...fractures, Gustilo type IIIC cases are particularly challenging due to the concomitant occurrence of neurovascular injuries and soft tissue defects. This study aimed to assess factors that affect union time and complications in Gustilo IIIC tibial fractures.
Methods
Patients who presented at our center with IIIC open tibial fractures from January 2000 to October 2020 were eligible for this retrospective analysis. Patient demographics, fracture characteristics, and the timing, number, and type of surgical intervention were documented. Outcomes of interest included union time, occurrence of osteomyelitis, and amputation. We performed univariate analyses including chi‐squared test, Fischer's exact test, analysis of variance, and Kruskal–Wallis test based on the normality of the data and multivariate analyses including Cox proportional hazards model and logistic regression analyses.
Results
Fifty‐eight patients were enrolled and grouped by fracture healing time; eight had timely union (13.8%); 27 had late union (46.6%); eight had delayed union (13.8%); three had nonunion (5.2%); and 12 underwent amputation (20.7%). Nine fractures (15.5%) were complicated by osteomyelitis. Union time was prolonged in cases of triple arterial injury, distal third fractures, multiple trauma with injury severity score (ISS) ≥ 16 points, and increased bone defect length. Additionally, a bone gap >50 mm, diabetes mellitus, low body mass index, and triple arterial injury in the lower leg were significant risk factors for amputation. A time from injury to definitive soft tissue coverage of more than 22 days was the major risk factor for osteomyelitis. A scoring system to predict union time was devised and the predicted probability of union within 2 years was stratified based on this score.
Conclusion
IIIC tibial fractures involving the distal third of the tibia, fractures with bone defects, triple arterial injury, and multiple trauma with ISS ≥16 points demonstrated delayed union, and an effective prediction system for union time was introduced in this study. Early soft tissue coverage can reduce the risk of osteomyelitis. Finally, diabetes and severe bone and soft tissue defects pose a higher risk of amputation.
Open type IIIC tibial fractures involving the distal third of the tibia, fractures with bone defects, triple arterial injury, and multiple trauma with ISS ≥16 points demonstrated delayed union, and an effective prediction system for union time was introduced in this study. Early soft tissue coverage can reduce the risk of osteomyelitis. Finally, diabetes and severe bone and soft tissue defects pose a higher risk of amputation.
Tonsillar herniation is a rare and seldom reported complication after lumboperitoneal (LP) shunting. There have been only few reports that have presented possible options for treatment with varying ...degrees of success. In this report, we describe a rare case of tonsillar herniation after LP shunting and review related literature. A 17-year-old girl with hydrocephalus related to a traumatic brain injury underwent implantation of an adjustable pressure shunt (valve setting2.5) and a small lumen peritoneal catheter via the L4-L5 interspinal space. One month later, she was admitted to the emergency room with a Glasgow Coma Scale score ofE1M1Vt and dilated pupil. Image studies demonstrated new-onset tonsillar herniation and a mild cervical syrinx. Emergent suboccipital decompressive craniectomy, C1 laminectomy, and duraplasty were performed. This was followed with ligation of the LP shunt and implantation of a ventriculoperitoneal (VP) shunt a few days later. The patient's Glasgow Coma Scale score gradually recovered to 6, which was her previous neurologic status. Tonsillar herniation as a complication after LP shunting is best treated with decompression, ligation or removal of the LP shunt, and a shift to a VP shunt. The tonsillar herniation should be rapidly addressed to avoid persistent symptoms or progression of the neurologic deficits.
An innovative immunosuppressant with a minimally invasive delivery system has emerged in the biomedical field. The application of biodegradable and biocompatible polymer forms, such as hydrogels, ...scaffolds, microspheres, and nanoparticles, in transplant recipients to control the release of immunosuppressants can minimize the risk of developing unfavorable conditions. In this review, we summarized several studies that have used implantable immunosuppressant delivery to release therapeutic agents to prolong allograft survival. We also compared their applications, efficacy, efficiency, and safety/side effects with conventional therapeutic-agent administration. Finally, challenges and the future prospective were discussed. Collectively, this review will help relevant readers understand the different approaches to prevent transplant rejection in a new era of therapeutic agent delivery.
A White Random Laser Chang, Shu-Wei; Liao, Wei-Cheng; Liao, Yu-Ming ...
Scientific reports,
02/2018, Volume:
8, Issue:
1
Journal Article
Peer reviewed
Open access
Random laser with intrinsically uncomplicated fabrication processes, high spectral radiance, angle-free emission, and conformal onto freeform surfaces is in principle ideal for a variety of ...applications, ranging from lighting to identification systems. In this work, a white random laser (White-RL) with high-purity and high-stability is designed, fabricated, and demonstrated via the cost-effective materials (e.g., organic laser dyes) and simple methods (e.g., all-solution process and self-assembled structures). Notably, the wavelength, linewidth, and intensity of White-RL are nearly isotropic, nevertheless hard to be achieved in any conventional laser systems. Dynamically fine-tuning colour over a broad visible range is also feasible by on-chip integration of three free-standing monochromatic laser films with selective pumping scheme and appropriate colour balance. With these schematics, White-RL shows great potential and high application values in high-brightness illumination, full-field imaging, full-colour displays, visible-colour communications, and medical biosensing.
One new dibenzocycloheptene, validinol (
), and one butanolide firstly isolated from the natural source, validinolide (
), together with 17 known compounds were isolated from the stem of
. Among the ...isolates, lincomolide A (
), secosubamolide (
), and cinnamtannin B1 (
) exhibited potent inhibition on both superoxide anion generation (IC
values of 2.98 ± 0.3 µM, 4.37 ± 0.38 µM, and 2.20 ± 0.3 µM, respectively) and elastase release (IC
values of 3.96 ± 0.31 µM, 3.04 ± 0.23 µM, and 4.64 ± 0.71 µM, respectively) by human neutrophils. In addition, isophilippinolide A (
), secosubamolide (
), and cinnamtannin B1 (
) showed bacteriostatic effects against
in in vitro study, with minimal inhibitory concentration (MIC) values at 16 μg/mL, 16 μg/mL, and 500 μg/mL, respectively. Further investigations using the in vivo ear
infection model showed that the intraperitoneal administration of the major component cinnamtannin B1 (
) reduced immune cell infiltration and pro-inflammatory cytokines TNF-α and IL-6 at the infection sites. The results demonstrated the potential of cinnamtannin B1 (
) for acne therapy. In summary, these results demonstrated the anti-inflammatory potentials of Formosan
during bacterial infections.
Vacuum‐sublimed inorganic cesium lead halide perovskite thin films are prepared and integrated in all‐vacuum‐deposited solar cells. Special care is taken to determine the stoichiometric balance of ...the sublimation precursors, which has great influence on the device performance. The mixed halide devices exhibit exceptional stabilized power conversion efficiency (11.8%) and promising thermal and long‐term stabilities.
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system characterized by relapses and autoimmunity caused by antibodies against the astrocyte water ...channel protein aquaporin-4. Over the past decade, there have been significant advances in the biologic knowledge of NMOSD, which resulted in the IDENTIFICATION of variable disease phenotypes, biomarkers, and complex inflammatory cascades involved in disease pathogenesis. Ongoing clinical trials are looking at new treatments targeting NMOSD relapses. This review aims to provide an update on recent studies regarding issues related to NMOSD, including the pathophysiology of the disease, the potential use of serum and cerebrospinal fluid cytokines as disease biomarkers, the clinical utilization of ocular coherence tomography, and the comparison of different animal models of NMOSD.
In the modern society when intelligent mobile devices become popular, the Internet breaks through the restrictions on time and space and becomes a ubiquitous learning tool. Designing teaching ...activity for digital learning and flexibly applying technology tools are the key issues for current information technology integrated education. In this study, students are tested and proceeded questionnaire survey to understand the opinions about digital learning. To effectively achieve the research objectives and test the research hypotheses, quasi-experimental research is applied in this study. Total 116 students in 4 classes are selected as the research subjects for the instructional research. The research results conclude that 1. digital learning presents better positive effects on learning motivation than traditional teaching does, 2. digital learning shows better positive effects on learning outcome than traditional teaching does, 3. learning motivation reveals significantly positive effects on learning effect in learning outcome, and 4. learning motivation appears remarkably positive effects on learning gain in learning outcome. It is expected to combine with current teaching trend and utilize the advantages of digital learning to develop practicable teaching strategies for the teaching effectiveness.
PDF
