513 research outputs found

    A new MOF-5 homologue for selective separation of methane from C<sub>2</sub> hydrocarbons at room temperature

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    A new MOF-5 homologue compound UTSA-10 has been obtained under solvothermal conditions from a mixture of Zn(NO3)2⋅6H2O and commercially available linker, 2-methylfumaric acid, in N,N-dimethylformamide. The moderate surface area and suitable pore sizes enable the activated UTSA-10a to separate methane from C2 hydrocarbons at room temperature

    Microglial refinement of A-fibre projections in the postnatal spinal cord dorsal horn is required for normal maturation of dynamic touch

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    Sensory systems are shaped in postnatal life by the refinement of synaptic connections. In the dorsal horn of the spinal cord, sensory circuits undergo postnatal activity dependent reorganisation, including the retraction of primary afferent A-fibres from superficial to deeper laminae which is accompanied by decreases in cutaneous sensitivity. Here we show that microglia, the resident immune cells in the CNS, phagocytose A-fibre terminals in superficial laminae in the first weeks of life. Genetic perturbation of microglial engulfment at that time prevents the normal process of A-fibre retraction, resulting in increased sensitivity of dorsal horn cells to dynamic tactile cutaneous stimulation, and behavioural hypersensitivity to dynamic touch. Thus, functional microglia are necessary for normal postnatal development of dorsal horn sensory circuits. In the absence of microglial engulfment, superfluous A-fibre projections remain in the dorsal horn and the balance of sensory connectivity is disrupted, leading to lifelong hypersensitivity to dynamic touch

    Deep muscularis propria tumor invasion without lymph node metastasis as a unique subclassification of stage IB gastric cancer: a retrospective study

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    BACKGROUND: The prognosis difference based on the depth of tumor muscularis propria invasion in gastric cancer (GC) was still debated, and therapy strategy for stage IB GC patient required further investigation. METHODS: A total of 380 patients with pT2 GC after radical surgery were retrospectively analyzed, including 185 in superficial muscularis propria (sMP) group and 195 in deep muscularis propria (dMP) group. RESULTS: The overall survival (OS) was significantly better for patients in sMP group than for patients in dMP group (P = 0.007). In multivariate analysis, depth of tumor invasion, pN stage, age, primary location, positive expression of p53, elevated maximal LDH, elevated initial CA19-9 and AFP level were independent prognostic factors for OS. The sMP group had a significantly better OS than dMP group (P = 0.014) in pN0 stage. After further stratification, the survival outcomes were not significantly different between deep muscularis propria tumor invasion without lymph node metastasis (dMPN0) group (stage IB) and superficial muscularis propria tumor invasion with stage 1-2 lymph node metastasis (sMPN1-2) group (stage II) (P = 0.100). Patients with adjuvant chemotherapy had a statistically better survival than those without in dMPN0 group (P = 0.045) and dMPN0 patients with adjuvant chemotherapy had better OS than sMPN1-2 patients (P = 0.015). In addition, greater postoperative survival could be observed in sMPN0 patients than dMPN0 patients in p53-positive group (P = 0.002), and similar OS could be seen between dMPN0 patients with p53-positive and T2N1-2 patients (P = 0.872). CONCLUSION: As a unique subclassification of stage IB GC, appropriate adjuvant chemotherapy should be considered for patients with dMPN0 stage. In addition, positive expression of p53, elevated LDH could be potential factors in identifying the different prognoses for stage IB GC patients

    A tryst of ‘blood pressure control- sex- comorbidities’:the odyssey of basic public health services in Yunnan in quest for truth

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    Background: The Basic Public Health Service (BPHS), a recently announced free healthcare program, aims to combat the most prevalent Noncommunicable Disease-“Hypertension” (HTN)-and its risk factors on a nationwide scale. In China, there is a rife that HTN less impacts women during their lifetime. We, therefore, aimed to evaluate the sex disparity in hypertension patients with comorbidities among south-west Chinese and the contribution of BPHS to address that concern. Methods: We have opted for a multistage stratified random sampling method to enroll hypertensive patients of 35 years and older, divided them into BPHS and non-BPHS groups. We assessed the sex disparity in HTN patients with four major comorbidities- Dyslipidemia, Diabetes Mellitus (DM), Cardiovascular Disease (CVD), and Chronic Kidney Disease (CKD), and descriptive data were compiled. Odds ratios from logistic regression models estimated the effectiveness of BPHS in the management of HTN with comorbidities. Results: Among 1521 hypertensive patients,1011(66.5%) were managed in the BPHS group. The proportion of patients who had at least one comorbidity was 70.7% (95% confidence interval [CI]: 66.3-76.8%), patients aged 65 years and older were more likely to have coexisting comorbidities. Participants who received the BPHS showed significant blood pressure (BP) control with two comorbidities (odds ratio [OR] = 2.414, 95% CI: 1.276–4.570), three or more (OR = 5.500, 95%CI: 1.174–25.756). Patients with dyslipidemia and DM also benefited from BPHS in controlling BP (OR = 2.169, 95% CI: 1.430–3.289) and (OR = 2.785, 95%CI: 1.242–6.246), respectively. In certain high-income urban survey centers, there was sex differences in the HTN management provided by BPHS, with men having better BP control rates than women. Conclusions: Perhaps this is the first study in China to succinctly show the effectiveness and sex disparity regarding “management of hypertensive comorbidities”. This supports that the BPHS program plays a pivotal role in controlling BP, therefore should recommend the national healthcare system to give women a foremost priority in BPHS, especially to those from low-socioeconomic and low-scientific literacy regions.</p

    Design of non-fragile state estimators for discrete time-delayed neural networks with parameter uncertainties

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    This paper is concerned with the problem of designing a non-fragile state estimator for a class of uncertain discrete-time neural networks with time-delays. The norm-bounded parameter uncertainties enter into all the system matrices, and the network output is of a general type that contains both linear and nonlinear parts. The additive variation of the estimator gain is taken into account that reflects the possible implementation error of the neuron state estimator. The aim of the addressed problem is to design a state estimator such that the estimation performance is non-fragile against the gain variations and also robust against the parameter uncertainties. Sufficient conditions are presented to guarantee the existence of the desired non-fragile state estimators by using the Lyapunov stability theory and the explicit expression of the desired estimators is given in terms of the solution to a linear matrix inequality. Finally, a numerical example is given to demonstrate the effectiveness of the proposed design approach

    Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors

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    BackgroundIt remains not well known whether skeletal muscle mass (SMM) loss has any impact on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer. We aimed to evaluate the association between SMM and clinical outcome of patients with advanced lung cancer receiving ICIs as first line or second line.Materials and MethodsFrom March 1st, 2019 to March 31st, 2021 at our hospital, 34 patients with advanced lung cancer treated with first-line or second-line ICIs were enrolled retrospectively. The estimation of skeletal muscle index (SMI) for sarcopenia was assessed at the level of the third lumbar vertebra (L3) on computed tomography (CT) images obtained within 4 weeks before initiation of ICIs treatment. The impact of sarcopenia (low SMI) on progression free survival (PFS) was analyzed using Kaplan-Meier method and log-rank tests. The effect of various variables on PFS was evaluated using Cox proportional hazards regression model with univariate and multivariate analysis. The impact on treatment response including objective response rate (ORR) and disease control rate (DCR) and immunotherapy related adverse events (irAEs) between patients with and without sarcopenia was compared by the chi-squared test. The comparison of SMI value between patients with objective response (OR), disease control (DC) and those without OR and DC was used student t-test or Mann-Whitney U test.ResultsBoth in univariate and multivariate analysis, sarcopenia and treatment lines were the predictive factors for PFS (p &lt; 0.05). Patients with sarcopenia had significantly shorter PFS than that of non-sarcopenic ones [6.57 vs. 16.2 months, hazard ratios (HR) = 2.947 and 3.542, and 95% confidence interval (CI): 1.123–13.183 and 1.11–11.308, p = 0.022 and 0.033]. No significant difference in ORR and irAEs was found. Patients with sarcopenia had lower DCR than those without sarcopenia. The mean SMI value of DCR group and non-DCR group was 32.94 ± 5.49 and 44.77 ± 9.06 cm2/m2, respectively (p = 0.008).ConclusionSarcopenia before immunotherapy might be a significant predictor for poor prognosis including shorter PFS and lower DCR in patients with advanced lung cancer treated with ICIs as first line or second line

    Isolation and Characterization of a Chinese Hamster Ovary Heparan Sulfate Cell Mutant Defective in Both Met Receptor Binding and Hepatocyte Growth Factor NK1/Met Signaling

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    Background/Aims: The up-regulation of hepatocyte growth factor/receptor, HGF/Met, signal transduction is observed in most of human cancers. Specific heparan sulfate structures enhance the HGF/Met signaling at both cell and animal-based model systems. Biochemical studies indicate that heparan sulfate interacts with HGF and a natural occurring splicing variant NK1 of HGF with similar affinity. However, it is currently unknown if cell surface heparan sulfate binds to Met at physiological conditions and if specific cell surface heparan sulfate structures are required for effective HGF/Met or NK1/Met signaling. Methods: An established flow sorting strategy was used to isolate a soluble Met recombinant protein-binding positive or negative CHO cell clones different only in specific heparan sulfate structures. The cell surface bindings were imaged by confocal microscopy and flow cytometry analysis. Glucosamine vs. galactosamine contents from media-, cell surface-, and cell association glycosaminoglycans were quantified by HPLC. 35S-sulfate labeled glycosaminoglycans were characterized by anion exchange and size-exclusion HPLC. Heparan sulfate disaccharide compositions were determined by HPLC-MS analysis. Western blot analyses of MAPK-p42/44 were used to monitor HGF- and NK1-facillated Met signaling. Results: CHO-Positive but not CHO-Negative cell surface heparan sulfate bound to Met recombinant protein and HGF/NK1 further promoted the binding. Overall glycosaminoglycan analysis results indicated that the CHO-Negative cells had reduced amount of heparan sulfate, shorter chain length, and less 6-O-sulfated disaccharides compared to that of CHO-Positive cells. Moreover, CHO-Negative cells were defective in NK1/Met but not HGF/Met signaling. Conclusions: This study demonstrated that soluble Met recombinant protein bound to cell surface HS at physiological conditions and a Met /HGF or NK1/HS ternary signaling complex might be involved in Met signaling. Shorter HS chains and reduced 6-O-sulfation might be responsible for reduced Met binding and the diminished NK1-initiated signaling in the CHO-Negative cells. The unique CHO-Positive and CHO-Negative cell clones established in current study should be effective tools for studying the role of specific glycosaminoglycan structures in regulating Met signaling. Such knowledge should be useful in developing glycosaminoglycan-based compounds that target HGF/Met signaling

    Pre-pandemic psychiatric disorders and risk of COVID-19 : a UK Biobank cohort analysis

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    This work is supported by the National Natural Science Foundation of China (81971262 to HS), West China Hospital COVID-19 Epidemic Science and Technology Project (HX-2019-nCoV-014 to HS), Sichuan University Emergency Grant (2020scunCoVyingji10002 to HS), and EU Horizon 2020 Research and Innovation Action Grant (847776 to UAV and FF). We thank the team members involved in West China Biomedical Big Data Center for Disease Control and Prevention for their support. Publisher Copyright: © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: Psychiatric morbidities have been associated with a risk of severe infections through compromised immunity, health behaviours, or both. However, data are scarce on the association between multiple types of pre-pandemic psychiatric disorders and COVID-19. We aimed to assess the association between pre-pandemic psychiatric disorders and the subsequent risk of COVID-19 using UK Biobank. Methods: For this cohort analysis, we included participants from UK Biobank who were registered in England and excluded individuals who died before Jan 31, 2020, (the start of the COVID-19 outbreak in the UK) or had withdrawn from UK Biobank. Participants diagnosed with a psychiatric disorder before Jan 31 were included in the group of individuals with pre-pandemic psychiatric disorders, whereas participants without a diagnosis before the outbreak were included in the group of individuals without pre-pandemic psychiatric disorders. We used the Public Health England dataset, UK Biobank hospital data, and death registers to collect data on COVID-19 cases. To examine the relationship between pre-pandemic psychiatric disorders and susceptibility to COVID-19, we used logistic regression models to estimate odds ratios (ORs), controlling for multiple confounders and somatic comorbidities. Key outcomes were all COVID-19, COVID-19 specifically diagnosed in inpatient care, and COVID-19-related deaths. ORs were also estimated separately for each psychiatric disorder and on the basis of the number of pre-pandemic psychiatric disorders. As a positive disease control, we repeated analyses for hospitalisation for other infections. Findings: We included 421 014 UK Biobank participants in our study and assessed their COVID-19 status between Jan 31 and July 26, 2020. 50 809 participants were diagnosed with psychiatric disorders before the outbreak, while 370 205 participants had no psychiatric disorders. The mean age at outbreak was 67·80 years (SD 8·12). We observed an elevated risk of COVID-19 among individuals with pre-pandemic psychiatric disorders compared with that of individuals without such conditions. The fully adjusted ORs were 1·44 (95% CI 1·28–1·62) for All COVID-19 cases, 1·55 (1·34–1·78) for Inpatient COVID-19 cases, and 2·03 (1·59–2·59) for COVID-19-related deaths. We observed excess risk, defined as risk that increased with the number of pre-pandemic psychiatric disorders, across all diagnostic categories of pre-pandemic psychiatric disorders. We also observed an association between psychiatric disorders and elevated risk of hospitalisation due to other infections (OR 1·74, 95% CI 1·58–1·93). Interpretation: Our findings suggest that pre-existing psychiatric disorders are associated with an increased risk of COVID-19. These findings underscore the need for surveillance of and care for populations with pre-existing psychiatric disorders during the COVID-19 pandemic. Funding: National Natural Science Foundation of China.Peer reviewe

    Enhanced CO 2

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    A new NbO-type metal-organic framework ZJNU-40 incorporating highly polarized benzothiadiazole moieties exhibits a high CO2 uptake of 108 cm(3) g(-1) at 296 K and 1 atm, as well as good adsorption selectivities of CO2 over CH4 and N-2 at room temperature, which is superior to that of the analogous MOF NOTT-101
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