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Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder, in which rituximab (RTX) induces the best long-term effect among recommended second-line treatments. Nevertheless, the optimal regimen of RTX remains unclear. We herein conducted a prospective, multicenter, open-label, randomized controlled trial to compare the efficacy and safety of RTX at two different dosage regimens in patients with corticosteroid-resistant or relapsed ITP. Recruited patients were randomly assigned (1:1) to receive either RTX at a repeated low dose (100 mg weekly for 4 weeks, LD-RTX) or at a single dose (375 mg/m

The association of previous hepatitis B virus (HBV) exposure [hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (anti-HBc/HBcAb) positive] with disease severity and decision on treatment option in primary immune thrombocytopenia (ITP) patients remains unclear. Data from 725 patients diagnosed with ITP were analyzed to elucidate the association between anti-HBc serological status and disease severity. Data from a published prospective study [high-dose dexamethasone (HD-DXM), HD-DXM plus recombinant human thrombopoietin, NCT01734044] and two retrospective studies (standard-dose and low-dose rituximab) were rearranged to evaluate the impact of anti-HBc serological status on the response and outcome to ITP-specific treatments and the risk of HBV reactivation related to these treatments. The prevalence of HBsAg- HBcAb+ and HBsAg- HBcAb- in ITP patients was 51·03% and 48·97% respectively. Compared to the HBsAg- HBcAb- group, patients in the HBsAg- HBcAb+ group had lower platelet count, higher bleeding score, and longer hospitalization (P = 0·002, 0·033, and 0·008 respectively). Moreover, the initial complete response rate of HBsAg- HBcAb+ patients was lower than that of HBsAg- HBcAb- patients (45·2% vs 59·8%, P = 0·027). In conclusion, previous HBV exposure was correlated with disease severity and hospitalization in ITP patients. Anti-HBc positivity may be considered as a predictor for poor response to ITP-specific treatments.

Immune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease, in which the overactivation of T cells is crucial in the pathogenesis. Atorvastatin (AT), a lipid-lowering medicine, has shown promising immunomodulatory effects in certain inflammatory conditions. However, the immunoregulatory role of AT in ITP remains elusive. To investigate the effect of AT in the treatment of ITP, cluster of differentiation 4 (CD4)+ T cells were isolated from patients with ITP and cultured with different dosages of AT. We found that AT significantly inhibited cell proliferation, led to cell cycle arrest, induced apoptosis, and repressed the activation of CD4+ T cells in vitro. ITP murine models were then established, and results showed that AT treatment led to faster recovery of the platelet count to normal and exhibited comparable immunomodulatory function. Furthermore, we found the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT) and extracellular signal-regulated kinase (ERK), as well as activation of rat sarcoma virus (RAS) were all reduced dramatically after AT treatment in vitro. In conclusion, our present study demonstrated that AT could reinstate the functions of CD4+ T cells by inhibiting the excessive activation, proliferation, and survival of CD4+ T cells in ITP via the RAS/mitogen-activated protein kinase kinase (MEK)/ERK and the mTOR/phosphatidylinositol-3 kinase (PI3K)/AKT pathway. Therefore, we propose that AT could be used as a potential therapeutic option for ITP by restoring the over-activated cellular immunity.

1,4-Dicarbonyl compounds are intriguing motifs and versatile precursors in numerous pharmaceutical molecules and bioactive natural compounds. Direct incorporation of two carbonyl groups into a double bond at both ends is straightforward, but also challenging. Represented herein is the first example of 1,2-dicarbonylation of alkenes by photocatalysis. Key to success is that N(n-Bu)4 + not only associates with the alkyl anion to avoid protonation, but also activates the α-keto acid to undergo electrophilic addition. The α-keto acid is employed both for acyl generation and electrophilic addition. By tuning the reductive and electrophilic ability of the acyl precursor, unsymmetric 1,4-dicarbonylation is achieved for the first time. This metal-free, redox-neutral and regioselective 1,2-dicarbonylation of alkenes is executed by a photocatalyst for versatile substrates under extremely mild conditions and shows great potential in biomolecular and drug molecular derivatization.

Perovskite solar cells (PSCs) are the one of most promising photovoltaic technologies that can be achieved by a simple solution process. At the current stage, the key issues concern further improvements in efficiency and operational lifetime. Constructing a self-assembled perovskite structure with manipulated chemical and physical properties is a useful and effective strategy to solve these problems. Herein, we review the basic principles and the recent progress of spontaneous formation behaviors of heterostructured perovskite thin films. This concept provides insightful clues towards the design and fabrication of stable and efficient PSCs for the next-generation photovoltaics.

A direct strategy for the difunctionalization of alkenes, with acylation occurring at the more substituted alkene position, would be attractive for complex ketone synthesis. We report herein a reaction driven by a single photocatalyst that enables α-acylation in this way with the introduction of a fluoromethyl, alkyl, sulfonyl or thioether group at the β-position of the alkene with high chemo- and regioselectivity under extremely mild conditions. Crucial to the success of this method are rate differences in the kinetics of radical generation through single-electron transfer (SET) between different radical precursors and the excited photocatalyst (PC*). Thus, the β-position of the alkene is first occupied by the group derived from the radical precursor that can be generated most readily, and α-keto acids could be used as an electrophilic reagent for the α-acylation of alkenes.

The unicellular alga Chlamydomonas reinhardtii and the bacterium Pseudomonas protegens serve as a model to study the interactions between photosynthetic and heterotrophic microorganisms. P. protegens secretes the cyclic lipopeptide orfamide A that interferes with cytosolic Ca2+ homeostasis in C. reinhardtii resulting in deflagellation of the algal cells. Here, we studied the roles of additional secondary metabolites secreted by P. protegens using individual compounds and co-cultivation of algae with bacterial mutants. Rhizoxin S2, pyrrolnitrin, pyoluteorin, 2,4-diacetylphloroglucinol (DAPG) and orfamide A all induce changes in cell morphology and inhibit the growth of C. reinhardtii. Rhizoxin S2 exerts the strongest growth inhibition, and its action depends on the spatial structure of the environment (agar versus liquid culture). Algal motility is unaffected by rhizoxin S2 and is most potently inhibited by orfamide A (IC50 = 4.1 μM). Pyrrolnitrin and pyoluteorin both interfere with algal cytosolic Ca2+ homeostasis and motility whereas high concentrations of DAPG immobilize C. reinhardtii without deflagellation or disturbance of Ca2+ homeostasis. Co-cultivation with a regulatory mutant of bacterial secondary metabolism (ΔgacA) promotes algal growth under spatially structured conditions. Our results reveal how a single soil bacterium uses an arsenal of secreted antialgal compounds with complementary and partially overlapping activities.

Exosomes are released into extracellular fluids and have emerged as vital biological mediators in autoimmune diseases. Plasma-derived exosomes have been reported to take part in the pathogenesis of primary immune thrombocytopenia (ITP), but the protein and miRNA cargoes have not been entirely elucidated. Via proteomic analysis and RNA sequencing on plasma-derived exosomes from ITP patients and healthy controls, we found one upregulated exosomal protein (apolipoprotein E, ApoE), six downregulated exosomal miRNAs (miR-584-5p, miR-4433a-5p, miR-4433b-3p, miR-6842-3p, miR-130b-5p and miR-222-3p), and 10 upregulated exosomal miRNAs (miR-29a-3p, miR-142-5p, miR-16-2-3p, miR-29b-3p, miR-501-3p, miR-144-5p, miR-192-5p, miR-182-5p, miR-363-3p and miR-96-5p) in ITP patients. The elevated exosomal protein candidate ApoE in the ITP cohort was further validated using western blot. Via quantitative real-time polymerase chain reaction assays, three differentially expressed miRNAs (miR-584-5p, miR-142-5p and miR-29b-3p) were identified. This study provides direct evidence for a restricted signature of exosomal protein and miRNAs which distinguishes ITP from healthy controls. The results require further validation in larger independent ITP cohorts, which will provide insights into the potential pathophysiological significance of circulating exosomes in ITP.

This retrospective study aimed to evaluate the relationship between plasma autoantibody species and rhTPO response in adult ITP patients who failed the first-line treatments. Plasma anti-glycoprotein (GP) IIb/IIIa and anti-GPIb/IX autoantibodies were detected in 47·2% and 40·6% of the 123 patients, respectively. Overall response rate to rhTPO treatment in patients without anti-GPIb/IX autoantibodies was significantly higher than patients with anti-GPIb/IX autoantibodies (82·2% vs. 60·0%, P = 0·006). By contrast, no statistical difference in response rate was observed between patients with or without anti-GPIIb/IIIa autoantibodies (74·1% vs. 72·3%, P = 0·819). Therefore, the presence of anti-GPIb/IX autoantibodies might serve as a predictive factor for poor response to rhTPO treatment in ITP.

[3]Radialenes are the smallest carbocyclic structures with unusual topologies and cross-conjugated π-electronic structures. Here, we report a novel [1+1+1] cycloaddition reaction for the synthesis of aza[3]radialenes on the Ag(111) surface, where the steric hindrance of the chlorine substituents guides the selective and orientational assembling of the isocyanide precursors. By combining scanning tunneling microscopy, non-contact atomic force microscopy, and time-of-flight secondary ion mass spectrometry, we determined the atomic structure of the produced aza[3]radialenes. Furthermore, two reaction pathways including synergistic and stepwise are proposed based on density functional theory calculations, which reveal the role of the chlorine substituents in the activation of the isocyano groups via electrostatic interaction.

Bone marrow mesenchymal stem cell (BMSC) transplantation represents a promising repair strategy following spinal cord injury (SCI), although the therapeutic effects are minimal due to their limited neural differentiation potential. Polydatin (PD), a key component of the Chinese herb Polygonum cuspidatum, exerts significant neuroprotective effects in various central nervous system disorders and protects BMSCs against oxidative injury. However, the effect of PD on the neuronal differentiation of BMSCs, and the underlying mechanisms remain inadequately understood. In this study, we induced neuronal differentiation of BMSCs in the presence of PD, and analysed the Nrf2 signalling and neuronal differentiation markers using routine molecular assays. We also established an in vivo model of SCI and assessed the locomotor function of the mice through hindlimb movements and electrophysiological measurements. Finally, tissue regeneration was evaluated by H&E staining, Nissl staining and transmission electron microscopy. PD (30 μmol/L) markedly facilitated BMSC differentiation into neuron‐like cells by activating the Nrf2 pathway and increased the expression of neuronal markers in the transplanted BMSCs at the injured spinal cord sites. Furthermore, compared with either monotherapy, the combination of PD and BMSC transplantation promoted axonal rehabilitation, attenuated glial scar formation and promoted axonal generation across the glial scar, thereby enhancing recovery of hindlimb locomotor function. Taken together, PD augments the neuronal differentiation of BMSCs via Nrf2 activation and improves functional recovery, indicating a promising new therapeutic approach against SCI.

To investigate whether high body mass index (BMI) had adverse effects on the postoperative outcomes for patients who underwent anterior or posterior cervical fusion procedures. A literature search were conducted in PubMed, Embase, and Web of Science. Comparative or controlled studies that examined the influences of high BMI on postoperative outcomes after cervical fusion procedures were included. Using a fixed‐effect model or random‐effect model, the effects of high BMI were determined by weight mean difference (WMD) with 95% confidence interval (95% CI) or risk ratio (RR) with 95% CI. A total of seven studies were included in this meta‐analysis. The pooled estimate showed that high BMI was associated with longer hospital stay (WMD = 1.61 days, 95% CI: 0.51, 2.71; P = 0.004), longer surgical time (WMD = 4.55, 95% CI: 1.04, 8.07; P = 0.011), higher mortality rate (RR = 3.01, 95% CI: 2.75, 3.29; P

Spinal cord injury (SCI) leads to microvascular damage and the destruction of the blood spinal cord barrier (BSCB), which can progress into secondary injuries, such as apoptosis and necrosis of neurons and glia, culminating in permanent neurological deficits. BSCB restoration is the primary goal of SCI therapy, although very few drugs can repair damaged barrier structure and permeability. Sodium tanshinone IIA sulfonate (STS) is commonly used to treat cardiovascular disease. However, the therapeutic effects of STS on damaged BSCB during the early stage of SCI remain uncertain. Therefore, we exposed spinal cord microvascular endothelial cells to H2 O2 and treated them with different doses of STS. In addition to protecting the cells from H2 O2 -induced apoptosis, STS also reduced cellular permeability. In the in vivo model of SCI, STS reduced BSCB permeability, relieved tissue edema and hemorrhage, suppressed MMP activation and prevented the loss of tight junction and adherens junction proteins. Our findings indicate that STS treatment promotes SCI recovery, and should be investigated further as a drug candidate against traumatic SCI.

This paper hypothesizes and finds that firms audited by city‐industry specialists have more timely disclosures of contingent losses from litigation when there is no news coverage relating to the legal case prior to management disclosures. A closer examination reveals that this result is explained by the specialist auditors’ prior experience auditing clients in the same office and industry who are involved with litigation. In our setting, disclosures of litigation‐related contingent losses, we identify two kinds of knowledge generated from experience: industry knowledge and litigation knowledge. Industry knowledge helps auditors detect and correct poor implementation of guidance for litigation loss contingency disclosures. Auditors gain litigation knowledge from auditing clients in a given office and industry with previous involvement as defendants. Thus, the two types of knowledge interact in their effects on reporting outcomes. Les auteurs posent et demontrent l'hypothese selon laquelle les societes dont l'audit est assure par des auditeurs d'un meme bureau (local) qui sont des specialistes d'un secteur d'activite communiquent plus rapidement l'information relative aux pertes eventuelles decoulant d'un litige lorsque le litige en question n'est pas mediatise avant la publication d'information par la direction. Un examen plus attentif indique que cette observation s'explique par l'experience prealable que possedent les auditeurs specialises dans l'audit de clients du meme bureau et appartenant au meme secteur qui ont ete parties a un litige. Dans le contexte de l’etude, celui de la communication de l'information relative aux pertes eventuelles decoulant d'un litige, les auteurs definissent deux types de connaissance tiree de l'experience : la connaissance du secteur et la connaissance des litiges. La connaissance du secteur aide les auditeurs a deceler les deficiences dans l'application des directives en matiere de communication d'information relative aux pertes eventuelles decoulant de litiges et a y remedier. Les auditeurs acquierent leur connaissance des litiges aupres de leurs clients d'audit, d'un bureau et d'un secteur donnes, qui ont deja ete parties a des poursuites. Ces deux types de connaissance interagissent dans leurs repercussions sur l'information financiere.

Microarray showed that lncRNA RMST was differentially expressed in cervical cancer. Further experiments were conducted to detect the expression and biological function of RMST in triple-negative breast cancer (TNBC). Microarray was used to screen the differentially expressed lncRNAs in TNBC. QRT-PCR was applied to uncover the expression of RMST in TNBC tissues. The cell viability of RMST-transfected TNBC cells were probed by CKK-8 assay and colony formation assay. TUNEL assay was conducted to test the cell apoptosis and FCM assay was exerted to detect the cell cycle. The invasion and migration ability of transfected cells were examined by transwell assay. RMST played its biological function through regulating the mRNA or protein expression in cytoplasm. CCK-8 and colony formation assay unveiled that RMST could slow down the proliferation of TNBC cells to influence the tumor progression. TUNEL results revealed that RMST could enhance cell apoptosis in TNBC. The cell cycle detected by FCM assay indicated that RMST might induce the block of G0/G1 phase thus inhibiting TNBC cell proliferation. RMST overexpression could also restrain the invasion and migration abilities of TNBC cells. RMST played a role of tumor suppressor in TNBC through inhibiting cell proliferation, invasion and migration, enhancing cell apoptosis, and regulating cell cycle.

Objectives: To determine: (i) incidence and outcome of subarachnoid haemorrhage (SAH) in the general population; and (ii) proportions of SAH in both the general ED population and in ED patients presenting with headache. Methods: A population-based study in Queensland from January 2010 to December 2014 was conducted. Data were sourced from the Australian Bureau of Statistics, Queensland Hospital Admitted Patient Data Collection linked to the Queensland death registry and ED Information System. Admitted patients with SAH were identified from ICD-10-AM codes. Inter-hospital transfers and repeat admissions for previously diagnosed SAH were excluded. Pre-hospital deaths from SAH were included. ED patients with headache were identified from ICD-10-AM codes and finding ‘headache’ in the triage free-text entry. The incidence of SAH, inhospital mortality, proportions of SAH in the general ED population and ED patients with headache were calculated. Results: There were 1975 incident cases of SAH in admitted patients and 294 pre-hospital deaths from SAH. The incidence of SAH was 9.9 (95% confidence interval [CI] 9.5–10.4) per 100 000 person-years. The incidence standardised to the ‘World Standard Population’ was 7.0 per 100 000 person-years. The in-hospital mortality was 23.8% (95% CI 22.0–25.8%). SAH was found in 1407 (1.9%, 95% CI 1.8–2.0) of ED patients with headache. Overall, there were 2.4 (95% CI 2.3–2.5) SAH per 10 000 of all ED attendances. Conclusions: The incidence of SAH was similar to that previously reported for Australia. One in 50 ED patients with headache had SAH. Ten in 50 000 ED attendances had a SAH. These estimates can assist in the risk assessment for SAH.

A highly transparent NiO layer was prepared by a solution processing method with nickel(II) 2-ethylhexanoate in non-polar solvent and utilized as HTM in perovskite solar cells. Excellent optical transmittance and the matched energy level lead to the enhanced power conversion efficiency (PCE, 18.15 %) than that of conventional sol-gel-processed NiO-based device (12.98 %).

Cucumber (Cucumis sativus) is an agronomically important vegetable with indeterminant growth habit, in which leaves are produced from the shoot apical meristem (SAM), and unisexual flowers are generated from the leaf axils. LEAFY (LFY) and its homologs have been shown to play important roles in promoting flower development and branching. The LFY homolog gene CsLFY was cloned in cucumber. Molecular biology, developmental biology and biochemical tools were combined to explore the biological function of the LFY homologous gene CsLFY in cucumber. CsLFY was expressed in the SAM, floral meristem and floral organ primordia. Ectopic expression of CsLFY rescued the phenotype of the lfy-5 mutant in Arabidopsis. Knockdown of CsLFY by RNA interference (RNAi) led to defective shoot development and premature discontinuance of leaf initiation in cucumber. Transcription of CsWUS and putative CsLFY target genes including CsAP3 and CUM1 were significantly reduced in the CsLFY-RNAi lines. Further biochemical analyses indicated that CsLFY physically interacts with CsWUS in cucumber. These data suggested that CsLFY has a novel function in regulating shoot meristem maintenance through interaction with CsWUS, and promotes flower development via activation of CsAP3 and CUM1 in cucumber.

Objective The aim of this study was to understand what factors influence patients’ choice between public and private hospital ED and the relative weight of those factors among adult patients with private health insurance in Australia. Methods A survey of 280 patients was conducted in four public and private hospitals’ EDs in Brisbane between May and August 2015. The survey included information about respondent's demographics, nature of illness, decision-making, attitudes and choice. Independent t-test and Pearson's χ²-test were used to identify binary associations, and logistic regression was used to determine what factors influence patients’ choice. Results Patients who agreed that ‘long waiting time is a barrier to access public hospital ED’ were twice as likely to choose private hospitals (odds ratio [OR] 2.172, P = 0.001). Alternatively patients who did not consider that ‘there were long waiting times in public hospital ED’ were less likely to access private hospitals (OR 0.200, P = 0.003). More public hospital patients (70.7%) than private hospital patients (56.4%) (P = 0.015) agreed that ‘out-of-pocket payment is a barrier to accessing private hospital ED’. Patients attending private hospitals rated the quality of service higher than those attending public hospitals (OR 1.26, P = 0.001). Conclusion Longer waiting times in public EDs is the principal issue considered by patients choosing private EDs and the out-of-pocket payment for accessing private EDs is the principal issue considered by public ED patients. The study suggests that addressing the out-of-pocket payments will attract more patients with private health insurance to access private EDs.