Aim: Although a lower level of non-high-density lipoprotein cholesterol (HDL-C) was reported to be inversely associated with spontaneous intracranial hemorrhage (ICH), no enough evidence has verified ...whether lipid profiles modify hemorrhagic transformation and functional outcomes in patients with acute ischemic treated with thrombolysis.Methods: This multicenter cohort study included 2373 patients with acute ischemic stroke treated with intravenous thrombolysis between December 2004 and December 2016. Of these, 1845 patients were categorized into either the hyperlipidemia or non-hyperlipidemia group. Symptomatic ICH (SICH) rates within 24-36 h of thrombolytic onset and functional outcomes at 30 and 90 days were longitudinally surveyed. Models of predicting hemorrhagic transformation were used to validate our findings.Results: For enrolled 1845 patients, SICH rates were ≥2-fold reduced for the hyperlipidemia group by the NINDS (adjusted RR: 0.488 0.281–0.846, p=0.0106), the ECASS II (adjusted RR: 0.318 0.130-0.776, p=0.0119), and SITS-MOST standards (adjusted RR: 0.214 0.048-0.957, p=0.0437). The favorable functional rates between the two groups were not significantly different. Lower levels of LDL-C were showed in robust association with SICH. With a cut-off LDL-C value of ＜130 mg/dL, new models are more robust and significant in predicting hemorrhagic transformation within 24-36 h.Conclusions: This study supports the strong association between reduced LDL-C and increased SICH, but not for functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. LDL-C level of ＜130 mg/dL is supposed to a candidate marker for predicting SICH within 24-36 h.
A White Random Laser Chang, Shu-Wei; Liao, Wei-Cheng; Liao, Yu-Ming ...
Scientific reports,
02/2018, Letnik:
8, Številka:
1
Journal Article
Recenzirano
Odprti dostop
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.
Neoadjuvant immunotherapy and chemotherapy have improved the major pathological response (MPR) in patients with early-stage operable non-small cell lung cancer (NSCLC). This study aimed to assess ...whether the presence of targetable driver mutations affects the efficacy of the combination of immunotherapy and chemotherapy. We enrolled patients with early-stage operable NSCLC who received preoperative neoadjuvant therapy between January 1, 2017, and December 30, 2020. Neoadjuvant therapy was delivered with platinum-doublet chemotherapy; moreover, pembrolizumab was added at the attending physician's discretion based on patient's request. Pathological responses were assessed; moreover, disease-free survival was estimated. Next-generation sequencing was performed in case sufficient preoperative biopsy specimens were obtained. We included 23 patients; among them, 11 received a combination of neoadjuvant immunotherapy and chemotherapy while 12 received neoadjuvant chemotherapy alone. The MPR and pathological complete response rates were 54.5% and 27.3%, respectively, in patients who received a combination of neoadjuvant immunotherapy and chemotherapy. These rates were significantly higher than those in patients who only received neoadjuvant chemotherapy. Three patients in the combination group experienced disease recurrence during the follow-up period even though two of them showed an MPR. These three patients had targetable driver mutations, including an EGFR exon 20 insertion, EGFR exon 21 L858R substitution, and MET exon 14 skipping. Only one patient who remained disease-free had a targetable driver mutation. Among patients with early-stage operable NSCLC requiring neoadjuvant therapy, comprehensive genomic profiling is crucial before the administration of the combination of neoadjuvant immunotherapy and chemotherapy.
In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still ...poorly understood. In this study, we investigated the roles of cold‑inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC).
CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot.
Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)‑like population. Moreover, hyperthermia substantially improved the sensitivity of radiation‑resistant NPC cells and CSC‑like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti‑tumor‑killing activity of hyperthermia against NPC cells and CSC‑like cells, whereas ectopic expression of Cirbp compromised tumor‑killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC‑like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance.
Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.
Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Liver disorders have been recognized as one major health concern. Fucoidan, a sulfated polysaccharide extracted from the brown seaweed Fucus serratus, has previously been reported as an ...anti-inflammatory and antioxidant. However, the discovery and validation of its hepatoprotective properties and elucidation of its mechanisms of action are still unknown. The objective of the current study was to investigate the effect and possible modes of action of a treatment of fucoidan against thioacetamide (TAA)-induced liver injury in male C57BL/6 mice by serum biochemical and histological analyses. The mouse model for liver damage was developed by the administration of TAA thrice a week for six weeks. The mice with TAA-induced liver injury were orally administered fucoidan once a day for 42 days. The treated mice showed significantly higher body weights; food intakes; hepatic antioxidative enzymes (catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD)); and a lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and C-reactive protein (CRP) levels. Additionally, a reduced hepatic IL-6 level and a decreased expression of inflammatory-related genes, such as cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA was observed. These results demonstrated that fucoidan had a hepatoprotective effect on liver injury through the suppression of the inflammatory responses and acting as an antioxidant. In addition, here, we validated the use of fucoidan against liver disorders with supporting molecular data.
Global smartphone penetration has led to unprecedented addictive behaviors. The aims of this study are to develop diagnostic criteria of smartphone addiction and to examine the discriminative ability ...and the validity of the diagnostic criteria.
We developed twelve candidate criteria for characteristic symptoms of smartphone addiction and four criteria for functional impairment caused by excessive smartphone use. The participants consisted of 281 college students. Each participant was systematically assessed for smartphone-using behaviors by psychiatrist's structured diagnostic interview. The sensitivity, specificity, and diagnostic accuracy of the candidate symptom criteria were analyzed with reference to the psychiatrists' clinical global impression. The optimal model selection with its cutoff point of the diagnostic criteria differentiating the smartphone addicted subjects from non-addicted subjects was then determined by the best diagnostic accuracy.
Six symptom criteria model with optimal cutoff point were determined based on the maximal diagnostic accuracy. The proposed smartphone addiction diagnostic criteria consisted of (1) six symptom criteria, (2) four functional impairment criteria and (3) exclusion criteria. Setting three symptom criteria as the cutoff point resulted in the highest diagnostic accuracy (84.3%), while the sensitivity and specificity were 79.4% and 87.5%, respectively. We suggested determining the functional impairment by two or more of the four domains considering the high accessibility and penetration of smartphone use.
The diagnostic criteria of smartphone addiction demonstrated the core symptoms "impaired control" paralleled with substance related and addictive disorders. The functional impairment involved multiple domains provide a strict standard for clinical assessment.
Defect engineering represents a significant approach for atomically thick 2D semiconductor material development to explore the unique material properties and functions. Doping‐induced conversion of ...conductive polarity is particularly beneficial for optimizing the integration of layered electronics. Here, controllable doping behavior in palladium diselenide (PdSe2) transistor is demonstrated by manipulating its adatom‐vacancy groups. The underlying mechanisms, which originate from reversible adsorption/desorption of oxygen clusters near selenide vacancy defects, are investigated systematically via their dynamic charge transfer characteristics and scanning tunneling microscope analysis. The modulated doping effect allows the PdSe2 transistor to emulate the essential characteristics of photo nociceptor on a device level, including firing signal threshold and sensitization. Interestingly, electrostatic gating, acting as a neuromodulator, can regulate the adaptive modes in nociceptor to improve its adaptability and perceptibility to handle different danger levels. An integrated artificial nociceptor array is also designed to execute unique image processing functions, which suggests a new perspective for extension of the promise of defect engineered 2D electronics in simplified sensory systems toward use in advanced humanoid robots and artificial visual sensors.
Modulable conductive polarity is demonstrated in the PdSe2 ambipolar transistor by Se vacancy‐dominated defect engineering via laser irradiation. It endows the PdSe2 transistor‐based synaptic device with convertible plasticity to emulate the tunable adaptive features in the photo nociceptor, providing a new vista for the defect‐engineered van der Waals electronics to exploit novel applications toward advanced artificial intelligent machines.
The 3D printed bulk samples fabricated by selective laser melting (SLM) of the additive manufacturing technique are usually considered to be 3D isotropic in microstructures and mechanical responses. ...This study systematically investigates the anisotropic responses in terms of hardness and electrochemical resistance for the X-, Y- and Z-planes of the SLM Ti-6Al-4V bulk samples fabricated with the zigzag laser path strategy. Results show that all SLM planes exhibit no significant difference in Young's modulus compared to the mechanically rolled plate. However, the X-plane, referred to the cross-sectional plane perpendicular to the laser moving direction, is found ~20% lower hardness and the lowest corrosion resistance compared to the Y- and Z-planes. The underlying reasoning is researched and discussed. The microstructure observations indicate that artifact holes are induced in the X-plane due to un-uniform laser intensity distribution between two neighboring printing lines. Alternatively, the Y- and Z-planes exhibit dense morphology due to multiple heating while zigzag scanning. Experimental results also indicate that the SLM materials exhibit higher corrosion resistance than the commercial rolled materials.
The c.G6055A (p.G2019S) mutation in leucine-rich repeat kinase 2 (LRRK2) is the most prevalent genetic cause of Parkinson's disease (PD). CRISPR/Cas9-mediated genome editing by homology-directed ...repair (HDR) has been applied to correct the mutation but may create small insertions and deletions (indels) due to double-strand DNA breaks. Adenine base editors (ABEs) could convert targeted A·T to G·C in genomic DNA without double-strand breaks. However, the correction efficiency of ABE in LRRK2 c.G6055A (p.G2019S) mutation remains unknown yet. This study aimed to compare the mutation correction efficiencies and off-target effects between HDR and ABEs in induced pluripotent stem cells (iPSCs) carrying LRRK2 c.G6055A (p.G2019S) mutation.
A set of mutation-corrected isogenic lines by editing the LRRK2 c.G6055A (p.G2019S) mutation in a PD patient-derived iPSC line using HDR or ABE were established. The mutation correction efficacies, off-target effects, and indels between HDR and ABE were compared. Comparative transcriptomic and proteomic analyses between the LRRK2 p.G2019S iPSCs and isogenic control cells were performed to identify novel molecular targets involved in LRRK2-parkinsonism pathways.
ABE had a higher correction rate (13/53 clones, 24.5%) than HDR (3/47 clones, 6.4%). Twenty-seven HDR clones (57.4%), but no ABE clones, had deletions, though 14 ABE clones (26.4%) had off-target mutations. The corrected isogenic iPSC-derived dopaminergic neurons exhibited reduced LRRK2 kinase activity, decreased phospho-α-synuclein expression, and mitigated neurite shrinkage and apoptosis. Comparative transcriptomic and proteomic analysis identified different gene expression patterns in energy metabolism, protein degradation, and peroxisome proliferator-activated receptor pathways between the mutant and isogenic control cells.
The results of this study envision that ABE could directly correct the pathogenic mutation in iPSCs for reversing disease-related phenotypes in neuropathology and exploring novel pathophysiological targets in PD.
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