Aims/hypothesis
The aim of this work was to compare the glucose-lowering efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors between Asian and non-Asian patients with type 2 diabetes.
Methods
We ...searched MEDLINE, EMBASE, LILACS, CENTRAL, ClinicalTrials.gov and conference proceedings. Studies were eligible if they were randomised controlled trials with a treatment duration of at least 12 weeks, compared a DPP-4 inhibitor with a placebo as either monotherapy or oral combination therapy, had information on ethnicity and HbA
1c
values and were published or described in English. A systematic review and meta-analysis with a meta-regression analysis was conducted.
Results
Among 809 potentially relevant studies, 55 trials were included. A meta-analysis revealed that DPP-4 inhibitors lowered HbA
1c
to a greater extent in studies with ≥50% Asian participants (weighted mean difference WMD −0.92%; 95% CI −1.03, −0.82) than in studies with <50% Asian participants (WMD −0.65%; 95% CI −0.69, −0.60). The between-group difference was −0.26% (95% CI −0.36, −0.17,
p
< 0.001). The baseline BMI significantly correlated with the HbA
1c
-lowering efficacy of DPP-4 inhibitors. The RR of achieving the goal of HbA
1c
<7.0% (53.0 mmol/mol) was higher in studies with ≥50% Asian participants (3.4 95% CI 2.6, 4.7 vs 1.9 95% CI 1.8, 2.0). The fasting plasma glucose-lowering efficacy was higher with monotherapy in the Asian-dominant studies, but the postprandial glucose-lowering efficacy and changes in body weight were comparable between the two groups.
Conclusions/interpretation
DPP-4 inhibitors exhibit a better glucose-lowering efficacy in Asians than in other ethnic groups; this requires further investigation to understand the underlying mechanism, particularly in relation to BMI.
Aims
The leucine‐rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic cause of Parkinson's disease (PD). There is compelling evidence that PD is not only a brain disease but also a ...gastrointestinal disorder; nonetheless, its pathogenesis remains unclear. We aimed to develop human neural and intestinal tissue models of PD patients harbouring an LRRK2 mutation to understand the link between LRRK2 and PD pathology by investigating the gene expression signature.
Methods
We generated PD patient‐specific induced pluripotent stem cells (iPSCs) carrying an LRRK2 G2019S mutation (LK2GS) and then differentiated into three‐dimensional (3D) human neuroectodermal spheres (hNESs) and human intestinal organoids (hIOs). To unravel the gene and signalling networks associated with LK2GS, we analysed differentially expressed genes in the microarray data by functional clustering, gene ontology (GO) and pathway analyses.
Results
The expression profiles of LK2GS were distinct from those of wild‐type controls in hNESs and hIOs. The most represented GO biological process in hNESs and hIOs was synaptic transmission, specifically synaptic vesicle trafficking, some defects of which are known to be related to PD. The results were further validated in four independent PD‐specific hNESs and hIOs by microarray and qRT‐PCR analysis.
Conclusion
We provide the first evidence that LK2GS also causes significant changes in gene expression in the intestinal cells. These hNES and hIO models from the same genetic background of PD patients could be invaluable resources for understanding PD pathophysiology and for advancing the complexity of in vitro models with 3D expandable organoids.
Using three dimensional neural and intestinal organoids derived from induced pluripotent stem cells carrying a LRRK2 G2019S mutation and wild‐type controls has demonstrated differential gene expression implicating several cellular pathways in the pathogenesis of Parkinson's disease.
Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the ...prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.
Spin-orbit torques arising from the spin-orbit coupling of non-magnetic heavy metals allow electrical switching of perpendicular magnetization. However, the switching is not purely electrical in ...laterally homogeneous structures. An extra in-plane magnetic field is indeed required to achieve deterministic switching, and this is detrimental for device applications. On the other hand, if antiferromagnets can generate spin-orbit torques, they may enable all-electrical deterministic switching because the desired magnetic field may be replaced by their exchange bias. Here we report sizeable spin-orbit torques in IrMn/CoFeB/MgO structures. The antiferromagnetic IrMn layer also supplies an in-plane exchange bias field, which enables all-electrical deterministic switching of perpendicular magnetization without any assistance from an external magnetic field. Together with sizeable spin-orbit torques, these features make antiferromagnets a promising candidate for future spintronic devices. We also show that the signs of the spin-orbit torques in various IrMn-based structures cannot be explained by existing theories and thus significant theoretical progress is required.
Abstract Background Programmed death-ligand 1 (PD-L1) expression has been suggested as a potential predictive biomarker of response to anti-PD-1/PD-L1 therapy. In this study, we investigated whether ...the expression of PD-L1 in tumour cells is affected by neoadjuvant concurrent chemoradiotherapy (CCRT) or chemotherapy in oesophageal squamous cell carcinoma. Patients and methods Between 2004 and 2014, we collected the medical records of locally advanced oesophageal cancer patients consecutively diagnosed and treated with neoadjuvant CCRT or chemotherapy, followed by curative resection. PD-L1 expression in acquired tissue specimens was evaluated by immunohistochemistry using the H-score. The changes in PD-L1 expression between paired samples were evaluated and we also analysed PD-L1 expression in surgical tumour specimens to evaluate its prognostic role. Results Twenty-eight paired tumour tissues that were acquired before and after neoadjuvant therapy were available: 19 patients with CCRT and 9 with chemotherapy before complete oesophagectomy. The PD-L1 H-score increased significantly from baseline tumour tissues to surgical tumour tissues after neoadjuvant CCRT ( P = 0.007, median H-score from 28 to 52), whereas it decreased significantly after neoadjuvant chemotherapy ( P = 0.048, median H-score from 53 to 22). In a total of 73 patients, including 45 additional cases for the prognosis analysis, patients with higher PD-L1 H-scores (≥20) had poorer overall survival (median 16.7 versus 32.9 months, P = 0.02) than those with lower H-scores (<20). Conclusions PD-L1 expression in tumour cells increased in oesophageal cancer patients who received neoadjuvant CCRT. Further studies with more cases are necessary to validate these findings.
Abstract
Background
Apelin is an endogenous neuropeptide that binds to the G-protein-coupled receptor (APJ) and participates in a variety of physiological processes in the heart, lungs and other ...peripheral organs. Intriguingly, Pyr1-Apelin-13, a highly potent pyroglutamic form of apelin, has the potential to bind to and be degraded by angiotensin-converting enzyme 2 (ACE2). ACE2 is known to operate as a viral receptor in the early stages of severe acute respiratory coronavirus (SARS-CoV-2) infection.
Aim
This study aimed to determine if apelin protects against SARS-CoV-2 infection by inhibiting ACE2 binding to SARS-CoV-2 spike protein.
Design and methods
To determine whether Pyr1-Apelin-13 inhibits ACE2 binding to the SARS-CoV-2 spike protein (S protein), we performed a cell-to-cell fusion assay using ACE2-expressing cells and S protein-expressing cells and a pseudovirus-based inhibition assay. We then analyzed publicly available transcriptome data while focusing on the beneficial effects of apelin on the lungs.
Results
We found that Pyr1-Apelin-13 inhibits cell-to-cell fusion mediated by ACE2 binding to the S protein. In this experiment, Pyr1-Apelin-13 protected human bronchial epithelial cells, infected with pseudo-typed lentivirus-producing S protein, against viral infection. In the presence of Pyr1-Apelin-13, the level of viral spike protein expression was also reduced in a concentration-dependent manner. Transcriptome analysis revealed that apelin may control inflammatory responses to viral infection by inhibiting the nuclear factor kappa B pathway.
Conclusion
Apelin is a potential therapeutic candidate against SARS-CoV-2 infection.
Neutrino elastic scattering observation with NaI (NEON) is an experiment designed to detect neutrino-nucleus coherent scattering using reactor electron antineutrinos. NEON is based on an array of six ...NaI(Tl) crystals with a total mass of 13.3 kg, located at the tendon gallery that is 23.7 m away from a reactor core with a thermal power of 2.8 GW in the Hanbit nuclear power complex. The installation of the NEON detector was completed in December 2020, and since May 2021, the detector has acquired data at full reactor power. Based on the observed light yields of the NaI crystals of approximately 22, number of photoelectrons per unit keV electron-equivalent energy (keVee), and 6 counts/kg/keV/day background level at 2–6 keVee energy, coherent elastic neutrino-nucleus scattering (CE
ν
NS) observation sensitivity is evaluated as more than 3
σ
assuming 1-year reactor-on and 100 days reactor-off data, 0.2 keVee energy threshold, and 7 counts/keV/kg/day background in the signal region of 0.2
-
0.5 keVee. This paper describes the design of the NEON detector, including the shielding arrangement, configuration of NaI(Tl) crystals, and associated operating systems. The initial performance and associated sensitivity of the experiment are also presented.
AIMS: This study investigated the effects of sodium chloride (NaCl) and various acids, alone or in combination, on Shigella flexneri growth in laboratory medium and cucumber puree. METHODS AND ...RESULTS: Shigella flexneri was treated with various acids (acetic, citric, malic, tartaric, propionic, lactic and phosphoric acid) alone or with 3, 6 or 9% NaCl. Pronounced antagonistic effects were observed in Sh. flexneri treated with acetic or lactic acid in combination with 3% NaCl. Next, Sh. flexneri was pre‐exposed to 3% NaCl and then treated with various acids; acid‐stressed cells were then inoculated onto agar plates containing 3% NaCl. There was no significant difference in the reduction of Sh. flexneri, regardless of treatment (P > 0·05). Finally, Sh. flexneri was inoculated into cucumber puree to which various concentrations of acetic acid had been added with and without 3% NaCl. Antagonistic effects were observed with a treatment of either 0·5 or 1% acetic acid combined with 3% NaCl. CONCLUSIONS: Antagonistic effects were observed when Sh. flexneri was exposed to acetic or lactic acid with NaCl. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that depending on the type of acid, the addition of NaCl can increase the resistance of Sh. flexneri to acid treatments. This may provide useful information for developing methods of preserving acidified foods.
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