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Background and aimEarly diagnosis and treatment of intracerebral hemorrhage (ICH) is thought to be critical for improving outcomes. We examined whether racial or ethnic disparities exist in acute care processes in the first hours after ICH.MethodsWe performed a retrospective review of a prospectively collected cohort of consecutive patients with spontaneous primary ICH presenting to a single urban tertiary care center. Acute care processes studied included time to computerized tomography (CT) scan, time from CT to inpatient bed request, and time from bed request to hospital admission. Clinical outcomes included mortality, Glasgow Outcome Scale, and modified Rankin Scale.ResultsFour hundred fifty-nine patients presented with ICH between 2006 and 2018 and met inclusion criteria (55% male; 75% non-Hispanic White [NHW]; mean age of 73). In minutes, median time to CT was 43 (interquartile range [IQR] 28, 83), time to bed request was 62 (IQR 33, 114), and time to admission was 142 (IQR 95, 232). In a multivariable analysis controlling for demographic factors, clinical factors, and disease severity, race/ethnicity had no effect on acute care processes. English language, however, was independently associated with slower times to CT (β = 30.7 min, 95% CI 9.9 to 51.4, p = 0.004) and to bed request (β = 32.8 min, 95% CI 5.5 to 60.0, p = 0.02). Race/ethnicity and English language were not independently associated with worse outcome.ConclusionsWe found no evidence of racial/ethnic disparities in acute care processes or outcomes in ICH. English as first language, however, was associated with slower care processes.

Mosaic immunogens are bioinformatically engineered human immunodeficiency virus type 1 (HIV-1) sequences designed to elicit clade-independent coverage against globally circulating HIV-1 strains. This phase 1, double-blinded, randomized, placebo-controlled trial enrolled healthy HIV-uninfected adults who received 2 doses of a modified vaccinia Ankara (MVA)-vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naive (n = 15) and those who had received an HIV-1 vaccine (Ad26.ENVA.01) 4-6 years earlier (n = 10). We performed prespecified blinded cellular and humoral immunogenicity analyses at days 0, 14, 28, 84, 98, 112, 168, 270, and 365. All 50 planned vaccinations were administered. Vaccination was safe and generally well tolerated. No vaccine-related serious adverse events occurred. Both cellular and humoral cross-clade immune responses were elicited after 1 or 2 vaccinations in all participants in the HIV-1 vaccine-naive group. Env-specific responses were induced after a single immunization in nearly all subjects who had previously received the prototype Ad26.ENVA.01 vaccine. No safety concerns were identified, and multiclade HIV-1-specific immune responses were elicited. NCT02218125.

During operating period, the safety monitoring of artificial islands greatly relates to the stability of their enclosing structures and the safety of their production and operation. Combined with the development of the first safety monitoring automatic system for artificial islands in coastal areas in China, this article analyzes the characteristics of artificial islands safety monitoring during operating period. The relevant pre-warning indices and pattern are first put forward. The countermeasures for the engineering safety are hierarchically proposed so as to guide similar projects.

Background：Myocarditis is an uncommon but serious manifestation of systemic lupus erythematosus （SLE）.This study aimed to investigate clinical characteristics and outcomes of lupus myocarditis （LM） and to determine risk factors of LM in hospitalized Chinese patients with SLE.Methods：We conducted a retrospective case-control study.A total of 25 patients with LM from 2001 to 2012 were enrolled as the study group,and 1 O0 patients with SLE but without LM were randomly pooled as the control group.Univariable analysis was performed using Chi-square tests for categorical variables,and the Student＇s t-test or Mann-Whitney U-test was performed for continuous variables according to the normality.Results：LM presented as the initial manifestation of SLE in 7 patients （28％） and occurred mostly at earlier stages compared to the controls （20.88 ± 35.73 vs.44.08 ± 61.56 months,P =0.008）.Twenty-one patients （84％） experienced episodes of symptomatic heart failure.Echocardiography showed that 23 patients （92％） had decreased left ventricular ejection fraction （＜50％） and all patients had wall motion abnormalities.A high SLE Disease Activity Index was the independent risk factor in the development of LM （odds ratio =1.322,P ＜ 0.001）.With aggressive immunosuppressive therapies,most patients achieved satisfactory outcome.The in-hospital mortality was not significantly higher in the LM group than in the controls （4％ vs.2％,P =0.491）.Conclusions：LM could result in cardiac dysfunction and even sudden death.High SLE disease activity might potentially predict the occurrence of LM at the early stage of SLE.Characteristic echocardiographic findings could confirm the diagnosis of LM.Early aggressive immunosuppressive therapy could improve the cardiac outcome of LM.

An aluminum alloy （Al-Zn-Mg-Cu） subjected to deep cryogenic treatment （DCT） was systematically investigated. The results show that a DCT-induced phase transformation varies the microstructures and affects the mechanical properties of the Al alloy. Both Guinier-Preston （GP） zones and a metastableη′phase were observed by high-resolution transmission electron microscopy. The phenomenon of the second precipitation of the GP zones in samples subjected to DCT after being aged was observed. The viability of this phase transfor-mation was also demonstrated by first-principles calculations.

Aim： To study the effect of gum mastic, a natural resin, on the proliferation of androgen-independent prostate cancer PC-3 cells, and further investigate the mechanisms involved in this regulatory system, taking nuclear factor rd3 （NF-kB） signal as the target. Methods： 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay and a flow cytometer were used to detect the effect of gum mastic on the proliferation of PC-3 cells. Then, reporter gene assay, RT-PCR, and Western blotting were carried out to study the effects of gum mastic on the NF-kB protein level and the NF-kB signal pathway. The expression of genes involved in the NF-kB signal pathway, including cyclin Dl, inhibitors of kBs （Ik Bα）, and phosphorylated Akt （p-AKT）, were measured. In addition, transient transfection assays with the 5x NF-kB consensus sequence promoter was also used to test the effects of gum mastic. Results： Gum mastic inhibited PC-3 cell growth and blocked the PC-3 cell cycle in the Gl phase. Gum mastic also suppressed NF-kB activity in the PC-3 cells. The expression of cyclin Dl, a crucial cell cycle regulator and an NF-kB downstream target gene, was reduced as well. Moreover, gum mastic decreased the p-AKT protein level and increased the InBα protein level. Conclusion： Gum mastic inhibited the proliferation and blocked the cell cycle progression in PC-3 cells by suppressing NF-kB activity and the NF-kB signal pathway.

Mitochondrial dysfunction and impaired Ca 2+ handling are involved in the development of diabetic cardiomyopathy (DCM). Dynamic relative protein 1 (Drp1) regulates mitochondrial fission by changing its level of phosphorylation, and the Orai1 (Ca 2+ release-activated calcium channel protein 1) calcium channel is important for the increase in Ca 2+ entry into cardiomyocytes. We aimed to explore the mechanism of Drp1 and Orai1 in cardiomyocyte hypertrophy caused by high glucose (HG). We found that Zucker diabetic fat rats induced by administration of a high-fat diet develop cardiac hypertrophy and impaired cardiac function, accompanied by the activation of mitochondrial dynamics and calcium handling pathway-related proteins. Moreover, HG induces cardiomyocyte hypertrophy, accompanied by abnormal mitochondrial morphology and function, and increased Orai1-mediated Ca 2+ influx. Mechanistically, the Drp1 inhibitor mitochondrial division inhibitor 1 (Mdivi-1) prevents cardiomyocyte hypertrophy induced by HG by reducing phosphorylation of Drp1 at serine 616 (S616) and increasing phosphorylation at S637. Inhibition of Orai1 with single guide RNA (sgOrai1) or an inhibitor (BTP2) not only suppressed Drp1 activity and calmodulin-binding catalytic subunit A (CnA) and phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) expression but also alleviated mitochondrial dysfunction and cardiomyocyte hypertrophy caused by HG. In addition, the CnA inhibitor cyclosporin A and p-ERK1/2 inhibitor U0126 improved HG-induced cardiomyocyte hypertrophy by promoting and inhibiting phosphorylation of Drp1 at S637 and S616, respectively. In summary, we identified Drp1 as a downstream target of Orai1-mediated Ca 2+ entry, via activation by p-ERK1/2-mediated phosphorylation at S616 or CnA-mediated dephosphorylation at S637 in DCM. Thus, the Orai1–Drp1 axis is a novel target for treating DCM.

The escape of bladder cancer from immunosurveillance causes monotherapy to exhibit poor efficacy; therefore, designing a multifunctional nanoparticle that boosts programmed cell death and immunoactivation has potential as a treatment strategy. Herein, we developed a facile one-pot coprecipitation reaction to fabricate cluster-structured nanoparticles (CNPs) assembled from Fe 3 O 4 and iron chlorophyll (Chl/Fe) photosensitizers. This nanoassembled CNP, as a multifunctional theranostic agent, could perform red-NIR fluorescence and change the redox balance by the photoinduction of reactive oxygen species (ROS) and attenuate iron-mediated lipid peroxidation by the induction of a Fenton-like reaction. The intravesical instillation of Fe 3 O 4 @Chl/Fe CNPs modified with 4-carboxyphenylboronic acid (CPBA) may target the BC wall through glycoproteins in the BC cavity, allowing local killing of cancer cells by photodynamic therapy (PDT)-induced singlet oxygen and causing chemodynamic therapy (CDT)-mediated ferroptosis. An interesting possibility is reprogramming of the tumor microenvironment from immunosuppressive to immunostimulatory after PDT-CDT treatment, which was demonstrated by the reduction of PD-L1 (lower “off” signal to the effector immune cells), IDO-1, TGF-β, and M2-like macrophages and the induction of CD8 +  T cells on BC sections. Moreover, the intravesical instillation of Fe 3 O 4 @Chl/Fe CNPs may enhance the large-area distribution on the BC wall, improving antitumor efficacy and increasing survival rates from 0 to 91.7%. Our theranostic CNPs not only demonstrated combined PDT-CDT-induced cytotoxicity, ROS production, and ferroptosis to facilitate treatment efficacy but also opened up new horizons for eliminating the immunosuppressive effect by simultaneous PDT-CDT.

Aims/Introduction Maternal hyperglycemia leads to adverse pregnancy outcomes, and also subsequently affects both mothers and their offspring in later life. The prevalence of type 2 diabetes mellitus is increasing worldwide, and gestational diabetes mellitus (GDM) is also believed to be increasing. More precise nationwide and up‐to‐date data on GDM are required. Materials and Methods A population‐based retrospective cohort study was carried out with the Birth Certificate Application database and linked to the National Health Insurance Research Database to explore trends in the annual crude prevalence of GDM in all women who gave birth between 1 January 2004 and 31 December 2015 in Taiwan and their pregnancy outcomes. The registry is considered complete, reliable and accurate. Results A total of 2,468,793 births from 2,430,307 pregnancies were reported between 1 January 2004 and 31 December 2015. Finally, 2,053,305 pregnancies were included for further analysis. The annual prevalence of GDM increased by 1.8‐fold during the 12 years from 2004 to 2015, with a significant continuous increasing trend (from 7.6% to 13.4%, P < 0.001). The annual prevalence of GDM significantly increased in each age group (all trends P < 0.001), particularly for women with maternal ages of 31 years and older. Urbanization level, geographic risk factors and seasonal variations were also noted. Conclusion The annual prevalence of GDM increased by 1.8‐fold in the 12‐year period from 2004 to 2015 in Taiwan, with a significant continuous increasing trend (from 7.6% to 13.4%, P < 0.001). The annual prevalence of gestational diabetes mellitus increased by 1.8‐fold in the 12‐year period from 2004 to 2015 in Taiwan, with a significant continuous increasing trend (from 7.6% to 13.4%, P < 0.001).

Taraxasterol (TAS) is an active ingredient of Dandelion ( Taraxacum mongolicum Hand. -Mazz.), a medicinal plant that has long been used in China for treatment of inflammatory disorders. But the underlying mechanism for its therapeutic effects on inflammatory disorders is not completely clear. Inflammasome activation is a critical step of innate immune response to infection and aseptic inflammation. Among the various types of inflammasome sensors that has been reported, NLR family pyrin domain containing 3 (NLRP3) is implicated in various inflammatory diseases and therefore has been most extensively studied. In this study, we aimed to explore whether TAS could influence NLPR3 inflammasome activation in macrophages. The results showed that TAS dose-dependently suppressed the activation of caspase-1 in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin treatment, resulting in reduced mature interleukin-1β (IL-1β) release and gasdermin D (GSDMD) cleavage. TAS greatly reduced ASC speck formation upon the stimulation of nigericin or extracellular ATP. Consistent with reduced cleavage of GSDMD, nigericin-induced pyroptosis was alleviated by TAS. Interestingly, TAS time-dependently suppressed the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 signaling induced by LPS priming. Like TAS, both INK-128 (inhibiting both mTORC1 and mTORC2) and rapamycin (inhibiting mTORC1 only) also inhibited NLRP3 inflammasome activation, though their effects on mTOR signaling were different. Moreover, TAS treatment alleviated mitochondrial damage by nigericin and improved mouse survival from bacterial infection, accompanied by reduced IL-1β levels in vivo . Collectively, by inhibiting the NLRP3 inflammasome activation, TAS displayed anti-inflammatory effects likely through regulation of the mTOR signaling in macrophages, highlighting a potential action mechanism for the anti-inflammatory activity of Dandelion in treating inflammation-related disorders, which warrants further clinical investigation.