Plasmons in Pb nanowire arrays on Si(557): Between one and two dimensions

The plasmon dispersion in arrays of nanowires of Pb close to an average Pb coverage of one monolayer was determined on the Si(557) surface using electron energy loss spectroscopy with both high energy and momentum resolution. While we find purely one-dimensional (1D) plasmon losses at a Pb concentration of 1.31 monolayers (ML), measured with respect to the Si(111) surface concentration, the 1.2 and 1.4 ML coverages exhibit wavelength-dependent transitions from 1D to anisotropic 2D properties. However, due to the high anisotropy in the system at all coverages, the dispersion curves exhibit 1D characteristics in both directions. This behavior seems to be related to the Pb-induced refacetting of the Si(557) surface, which depends on Pb coverage. It changes both effective system sizes and coupling strength between miniterraces. © 2011 American Physical Society.Ministry of Education, Culture, Sports, Science, and Technology, Japa

A Large Portal Vein: A Rare Finding of Recent Portal Vein Thrombosis

Acute portal vein thrombosis (PVT) is rarely encountered by clinicians. The most common manifestation of acute PVT is sudden onset of abdominal pain. A computed tomography scan without contrast often shows a high-density material in the portal vein. After injection of contrast agents, absence of luminal enhancement and enlargement of the obstructed portal vein are shown. In this case report, we demonstrated a rare computed tomography finding in which the diameter of the main portal vein was enormously distended to 3-fold that of the aorta in a patient with recent PVT. Despite thrombolysis and anticoagulation were immediately given, portal venous recanalization was not achieved in the patient. After 5 years, variceal bleeding and ascites occurred and liver function had persistently deteriorated. Finally, he died of progressive liver failure. Considering this case, we suggest that an early decision for invasive interventional treatment might be necessary to both increase the rate of portal venous recanalization and improve prognosis, as anticoagulation and thrombolysis therapy failed to recanalize recent PVT

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution

Rationale: Trauma, surgery, and infection can cause severe inflammation. Both dysregulated inflammation intensity and duration can lead to significant tissue injuries, organ dysfunction, mortality, and morbidity. Anti-inflammatory drugs such as steroids and immunosuppressants can dampen inflammation intensity, but they derail inflammation resolution, compromise normal immunity, and have significant adverse effects. The natural inflammation regulator mesenchymal stromal cells (MSCs) have high therapeutic potential because of their unique capabilities to mitigate inflammation intensity, enhance normal immunity, and accelerate inflammation resolution and tissue healing. Furthermore, clinical studies have shown that MSCs are safe and effective. However, they are not potent enough, alone, to completely resolve severe inflammation and injuries. One approach to boost the potency of MSCs is to combine them with synergistic agents. We hypothesized that alpha-1 antitrypsin (A1AT), a plasma protein used clinically and has an excellent safety profile, was a promising candidate for synergism. Methods: This investigation examined the efficacy and synergy of MSCs and A1AT to mitigate inflammation and promote resolution, using in vitro inflammatory assay and in vivo mouse acute lung injury model. The in vitro assay measured cytokine releases, inflammatory pathways, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs) production by neutrophils and phagocytosis in different immune cell lines. The in vivo model monitored inflammation resolution, tissue healing, and animal survival. Results: We found that the combination of MSCs and A1AT was much more effective than each component alone in i) modulating cytokine releases and inflammatory pathways, ii) inhibiting ROS and NETs production by neutrophils, iii) enhancing phagocytosis and, iv) promoting inflammation resolution, tissue healing, and animal survival. Conclusion: These results support the combined use of MSCs, and A1AT is a promising approach for managing severe, acute inflammation

Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial

Background: In a phase 2 trial, lenvatinib, an inhibitor of VEGF receptors 1–3, FGF receptors 1–4, PDGF receptor α, RET, and KIT, showed activity in hepatocellular carcinoma. We aimed to compare overall survival in patients treated with lenvatinib versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma. Methods: This was an open-label, phase 3, multicentre, non-inferiority trial that recruited patients with unresectable hepatocellular carcinoma, who had not received treatment for advanced disease, at 154 sites in 20 countries throughout the Asia-Pacific, European, and North American regions. Patients were randomly assigned (1:1) via an interactive voice–web response system—with region; macroscopic portal vein invasion, extrahepatic spread, or both; Eastern Cooperative Oncology Group performance status; and bodyweight as stratification factors—to receive oral lenvatinib (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight <60 kg) or sorafenib 400 mg twice-daily in 28-day cycles. The primary endpoint was overall survival, measured from the date of randomisation until the date of death from any cause. The efficacy analysis followed the intention-to-treat principle, and only patients who received treatment were included in the safety analysis. The non-inferiority margin was set at 1·08. The trial is registered with ClinicalTrials.gov, number NCT01761266. Findings: Between March 1, 2013 and July 30, 2015, 1492 patients were recruited. 954 eligible patients were randomly assigned to lenvatinib (n=478) or sorafenib (n=476). Median survival time for lenvatinib of 13·6 months (95% CI 12·1–14·9) was non-inferior to sorafenib (12·3 months, 10·4–13·9; hazard ratio 0·92, 95% CI 0·79–1·06), meeting criteria for non-inferiority. The most common any-grade adverse events were hypertension (201 [42%]), diarrhoea (184 [39%]), decreased appetite (162 [34%]), and decreased weight (147 [31%]) for lenvatinib, and palmar-plantar erythrodysaesthesia (249 [52%]), diarrhoea (220 [46%]), hypertension (144 [30%]), and decreased appetite (127 [27%]) for sorafenib. Interpretation: Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma. The safety and tolerability profiles of lenvatinib were consistent with those previously observed

Abnormal Liver Function Tests Were Associated With Adverse Clinical Outcomes: An Observational Cohort Study of 2,912 Patients With COVID-19

Background and Aim: The impact of liver function test (LFTs) abnormality on adverse clinical outcomes in coronavirus disease 2019 (COVID-19) patients remains controversial. The aim of this study was to assess the impact of abnormal LFTs on clinical outcomes in a large cohort of hospitalized patients with COVID-19.Methods: We retrospectively collected data on 2,912 consecutive patients with COVID-19 who were admitted to a makeshift hospital in China between 5 February and 23 March 2020. The association between LFTs abnormalities (baseline and peak values) and clinical outcomes was measured by using Cox regression models.Results: On admission 1,414 patients (48.6%) had abnormal LFTs, with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) elevation in 662 (22.7%), 221 (7.6%), 52 (1.8%), 135 (4.6%), and 536 (18.5%) patients, respectively, and hypoalbuminemia in 737 (25.3%) patients. During a median 13 (IQR: 8–19) days of hospitalization, 61 patients (2.1%) died, 106 patients (3.6%) admitted to intensive care unit (ICU), and 75 patients (2.6%) required mechanical ventilation. After adjustment for confounders, baseline abnormal LFTs were independently associated with increased risks of mortality (adjusted HR 3.66, 95%CI 1.64–8.19, p = 0.002), ICU admission (adjusted HR 3.12 95%CI 1.86–5.23, p < 0.001), and mechanical ventilation (adjusted HR 3.00, 95%CI 1.63–5.52, p < 0.001), which was homogeneous across the severity of COVID-19 infection. Among the parameters of LTFs, the associations with the outcomes were more pronounced for AST and albumin abnormality. In contrast, ALT elevation was not significantly associated with those outcomes. Similar results were observed for peak values of LFTs during hospitalization.Conclusions: Abnormality of AST, albumin, TBIL, ALP, and GGT but not ALT were independently associated with adverse outcomes

Effects of ketogenic diet on the classification and functional composition of intestinal flora in children with mitochondrial epilepsy

The ketogenic diet (KD) has shown excellent performance in the treatment of refractory epilepsy, but how it works is not yet fully understood. Gut microbiota is associated with various neurological disorders through the brain-gut axis. Different dietary patterns have different effects on the composition and function of gut microbiota. Here, by analyzing fecal samples from some patients with mitochondrial epilepsy before and after KD treatment through 16SrRNA sequencing, we found that KD intervention reduced the abundance of Firmicutes in the patient’s gut, while the abundance of Bacteroidota increased in the KD group. LefSe analysis showed that Actinobacteriota, Phascolarctobacterium had significant advantages in the control group, while Bacteroides increased significantly after KD intervention, especially Bacteroides fragilis. Functional analysis showed that there were significant differences in 12 pathways in level 3. These changes suggest that KD can change the composition and diversity of the gut microbiota in patients and affect their function. Changes in specific bacterial groups in the gut may serve as biomarkers for the therapeutic effects of KD on epilepsy

Dual-Level Regulation of ACC Synthase Activity by MPK3/MPK6 Cascade and Its Downstream WRKY Transcription Factor during Ethylene Induction in Arabidopsis

Plants under pathogen attack produce high levels of ethylene, which plays important roles in plant immunity. Previously, we reported the involvement of ACS2 and ACS6, two Type I ACS isoforms, in Botrytis cinerea–induced ethylene biosynthesis and their regulation at the protein stability level by MPK3 and MPK6, two Arabidopsis pathogen-responsive mitogen-activated protein kinases (MAPKs). The residual ethylene induction in the acs2/acs6 double mutant suggests the involvement of additional ACS isoforms. It is also known that a subset of ACS genes, including ACS6, is transcriptionally induced in plants under stress or pathogen attack. However, the importance of ACS gene activation and the regulatory mechanism(s) are not clear. In this report, we demonstrate using genetic analysis that ACS7 and ACS11, two Type III ACS isoforms, and ACS8, a Type II ACS isoform, also contribute to the B. cinerea–induced ethylene production. In addition to post-translational regulation, transcriptional activation of the ACS genes also plays a critical role in sustaining high levels of ethylene induction. Interestingly, MPK3 and MPK6 not only control the stability of ACS2 and ACS6 proteins via direct protein phosphorylation but also regulate the expression of ACS2 and ACS6 genes. WRKY33, another MPK3/MPK6 substrate, is involved in the MPK3/MPK6-induced ACS2/ACS6 gene expression based on genetic analyses. Furthermore, chromatin-immunoprecipitation assay reveals the direct binding of WRKY33 to the W-boxes in the promoters of ACS2 and ACS6 genes in vivo, suggesting that WRKY33 is directly involved in the activation of ACS2 and ACS6 expression downstream of MPK3/MPK6 cascade in response to pathogen invasion. Regulation of ACS activity by MPK3/MPK6 at both transcriptional and protein stability levels plays a key role in determining the kinetics and magnitude of ethylene induction