Endocytosis triggers V-ATPase-SYK-mediated priming of cGAS activation and innate immune response.

The current view of nucleic acid-mediated innate immunity is that binding of intracellular sensors to nucleic acids is sufficient for their activation. Here, we report that endocytosis of virus or foreign DNA initiates a priming signal for the DNA sensor cyclic GMP-AMP synthase (cGAS)-mediated innate immune response. Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H+ pump (V-ATPase), where SYK is activated and then phosphorylates human cGASY214/215 (mouse cGasY200/201) to prime its activation. Upon binding to DNA, the primed cGAS initiates robust cGAMP production and mediator of IRF3 activation/stimulator of interferon genes-dependent innate immune response. Consistently, blocking the V-ATPase-SYK axis impairs DNA virus- and transfected DNA-induced cGAMP production and expression of antiviral genes. Our findings reveal that V-ATPase-SYK-mediated tyrosine phosphorylation of cGAS following endocytosis of virus or other cargos serves as a priming signal for cGAS activation and innate immune response.

AND-Logic Cascade Rolling Circle Amplification for Optomagnetic Detection of Dual Target SARS-CoV-2 Sequences.

DNA logic operations are accurate and specific molecular strategies that are appreciated in target multiplexing and intelligent diagnostics. However, most of the reported DNA logic operation-based assays lack amplifiers prior to logic operation, resulting in detection limits at the subpicomolar to nanomolar level. Herein, a homogeneous and isothermal AND-logic cascade amplification strategy is demonstrated for optomagnetic biosensing of two different DNA inputs corresponding to a variant of concern sequence (containing spike L452R) and a highly conserved sequence from SARS-CoV-2. With an "amplifiers-before-operator" configuration, two input sequences are recognized by different padlock probes for amplification reactions, which generate amplicons used, respectively, as primers and templates for secondary amplification, achieving the AND-logic operation. Cascade amplification products can hybridize with detection probes grafted onto magnetic nanoparticles (MNPs), leading to hydrodynamic size increases and/or aggregation of MNPs. Real-time optomagnetic MNP analysis offers a detection limit of 8.6 fM with a dynamic detection range spanning more than 3 orders of magnitude. The accuracy, stability, and specificity of the system are validated by testing samples containing serum, salmon sperm, a single-nucleotide variant, and biases of the inputs. Clinical samples are tested with both quantitative reverse transcription-PCR and our approach, showing highly consistent measurement results.

Comparison of approaches to control for intracranial volume in research on the association of brain volumes with cognitive outcomes.

Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain-wide association approach in the MRI substudy of UK Biobank (N = 41,964; mean age = 64.5 years), we used regression models to estimate the associations of 58 regional brain volumetric measures with eight cognitive outcomes, comparing no correction and four ICV correction approaches. Approaches evaluated included: no correction; dividing regional volumes by ICV (proportional approach); including ICV as a covariate in the regression (adjustment approach); and regressing the regional volumes against ICV in different normative samples and using calculated residuals to determine associations (residual approach). We used Spearman-rank correlations and two consistency measures to quantify the extent to which associations were inconsistent across ICV correction approaches for each possible brain region and cognitive outcome pair across 2320 regression models. When the association between brain volume and cognitive performance was close to null, all approaches produced similar estimates close to the null. When associations between a regional volume and cognitive test were not null, the adjustment and residual approaches typically produced similar estimates, but these estimates were inconsistent with results from the crude and proportional approaches. For example, when using the crude approach, an increase of 0.114 (95% confidence interval [CI]: 0.103-0.125) in fluid intelligence was associated with each unit increase in hippocampal volume. However, when using the adjustment approach, the increase was 0.055 (95% CI: 0.043-0.068), while the proportional approach showed a decrease of -0.025 (95% CI: -0.035 to -0.014). Different commonly used methods to correct for ICV yielded inconsistent results. The proportional method diverges notably from other methods and results were sometimes biologically implausible. A simple regression adjustment for ICV produced biologically plausible associations.

Enhancing the Catalytic Activity of Laccase@Copper-Metal-Organic Framework Nanofractal Microspheres: Synergistic Contribution of the Mass Transfer and Electron Transfer Pathway.

Metal-organic frameworks (MOFs) are limited by small pores and buried active sites, and their enzyme-like catalytic activity is still very low. Herein, laccase was employed as the organic component to construct laccase@Cu3(BTC)2 nanofractal microspheres. During the preparation process, laccase adsorbed Cu2+ by electrostatic attractive interaction, then combined with Cu2+ by coordination interaction, and finally induced the in situ growth of H3BTC2 in multiple directions by electrostatic repulsion. Interestingly, electrostatic repulsion was tuned efficiently by adjusting the Cu2+ concentration to obtain laccase@Cu3(BTC)2 nanofractal microspheres (nanosheet microspheres, nanorod microspheres, and nanoneedle microspheres). Laccase@Cu3(BTC)2 nanorod microspheres exhibited the highest catalytic efficiency, which was 14-fold higher than that of smooth microspheres. The mechanism of the improvement of catalytic activity in the degradation of BPA was proposed for the first time. The enhanced catalytic activity depended on the adsorption effect of the nanorod framework and dual cycle synergistic catalysis of Cu+/Cu2+ active sites, which accelerated substrate diffusion and electron transfer. The catalytic mechanism of enzyme@MOF nanofractal microspheres not only deepens our understanding of enzyme and MOF synergistic catalysis but also provides new insights into the design of catalysts.

Effects of different modalities of transcranial magnetic stimulation on post-stroke cognitive impairment: a network meta-analysis.

OBJECTIVE: The study aimed to evaluate, using a network meta-analysis, the effects of different transcranial magnetic stimulation (TMS) modalities on improving cognitive function after stroke. METHODS: Computer searches of the Cochrane Library, PubMed, Web of Science, Embass, Google Scholar, CNKI, and Wanfang databases were conducted to collect randomized controlled clinical studies on the use of TMS to improve cognitive function in stroke patients, published from the time of database construction to November 2023. RESULTS: A total of 29 studies and 2123 patients were included, comprising five interventions: high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS), intermittent theta rhythm stimulation (iTBS), sham stimulation (SS), and conventional rehabilitation therapy (CRT). A reticulated meta-analysis showed that the rankings of different TMS intervention modalities in terms of the Montreal Cognitive Assessment (MoCA) scores, Mini-Mental State Examination scores (MMSE), and Modified Barthel Index (MBI) scores were: HF-rTMS > LF-rTMS > iTBS > SS > CRT; the rankings of different TMS intervention modalities in terms of the event-related potential P300. amplitude scores were HF-rTMS > LF-rTMS > iTBS > CRT > SS; the rankings of different TMS intervention modalities in terms of the P300 latency scores were: iTBS > HF-rTMS > LF-rTMS > SS > CRT. Subgroup analyses of secondary outcome indicators showed that HF-rTMS significantly improved Rivermead Behavior Memory Test scores and Functional Independence Measurement-Cognitive scores. CONCLUSIONS: High-frequency TMS stimulation has a better overall effect on improving cognitive functions and activities of daily living, such as attention and memory in stroke patients.

Research on predicting hematoma expansion in spontaneous intracerebral hemorrhage based on deep features of the VGG-19 network.

PURPOSE: To construct a clinical noncontrastive computed tomography (NCCT) deep learning joint model for predicting early hematoma expansion (HE) after cerebral hemorrhage (sICH) and evaluate its predictive performance. METHODS: All 254 patients with primary cerebral hemorrhage from January 2017 to December 2022 in the General Hospital of the Western Theater Command were included. According to the criteria of hematoma enlargement exceeding 33% or the volume exceeding 6 ml, the patients were divided into the HE group and the hematoma non-enlargement (NHE) group. Multiple models and the 10-fold cross-validation method were used to screen the most valuable features and model the probability of predicting HE. The area under the curve (AUC) was used to analyze the prediction efficiency of each model for HE. RESULTS: They were randomly divided into a training set of 204 cases in an 8:2 ratio and 50 cases of the test set. The clinical imaging deep feature joint model (22 features) predicted the area under the curve of HE as follows: clinical Navie Bayes model AUC 0.779, traditional radiology logistic regression (LR) model AUC 0.818, deep learning LR model AUC 0.873, and clinical NCCT deep learning multilayer perceptron model AUC 0.921. CONCLUSION: The combined clinical imaging deep learning model has a high predictive effect for early HE in sICH patients, which is helpful for clinical individualized assessment of the risk of early HE in sICH patients.

Regulating Crystallization and Lead Leakage of Perovskite Solar Cell Via Novel Polyoxometalate-Based Metal-Organic Framework.

Despite the unprecedented progress in lead-based perovskite solar cells (PSCs), the toxicity and leakage of lead from degraded PSCs triggered by deep-level defects and poor crystallization quality increase environmental risk and become a critical challenge for eco-friendly PSCs. Here, a novel 2D polyoxometalate (POM)-based metal-organic framework (MOF) (C5 NH5 )4 (C3 N2 H5 )2 Zn3 (H8 P4 Mo6 O31 )2 ·2H2 O (POMOF) is ingeniously devised to address these issues. Note that the integration of POM endows POMOF with great advantages of electrical conductivity and charge mobility. Ordered POMOF induces the crystallization of high-quality perovskite film and eliminates lead-based defects to improve internal stability. The resultant PSCs achieve a superior power conversion efficiency (23.3%) accompanied by improved stability that maintains ≈90% of its original efficiency after 1600 h. Meanwhile, POMOF with phosphate groups effectively prevents lead leakage through in situ chemical anchoring and adsorption methods to reduce environmental risk. This work provides an effective strategy to minimize lead-based defects and leakage in sustainable PSCs through multi-functional POM-based MOF material.

Molecular subtypes predict therapeutic responses and identifying and validating diagnostic signatures based on machine learning in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a hematological tumor derived from hematopoietic stem cells. The aim of this study is to analyze the biological characteristics and identify the diagnostic markers of CML. We obtained the expression profiles from the Gene Expression Omnibus (GEO) database and identified 210 differentially expressed genes (DEGs) between CML and normal samples. These DEGs are mainly enriched in immune-related pathways such as Th1 and Th2 cell differentiation, primary immunodeficiency, T cell receptor signaling pathway, antigen processing and presentation pathways. Based on these DEGs, we identified two molecular subtypes using a consensus clustering algorithm. Cluster A was an immunosuppressive phenotype with reduced immune cell infiltration and significant activation of metabolism-related pathways such as reactive oxygen species, glycolysis and mTORC1; Cluster B was an immune activating phenotype with increased infiltration of CD4 + and CD8 + T cells and NK cells, and increased activation of signaling pathways such as interferon gamma (IFN-γ) response, IL6-JAK-STAT3 and inflammatory response. Drug prediction results showed that patients in Cluster B had a higher therapeutic response to anti-PD-1 and anti-CTLA4 and were more sensitive to imatinib, nilotinib and dasatinib. Support Vector Machine Recursive Feature Elimination (SVM-RFE), Least Absolute Shrinkage Selection Operator (LASSO) and Random Forest (RF) algorithms identified 4 CML diagnostic genes (HDC, SMPDL3A, IRF4 and AQP3), and the risk score model constructed by these genes improved the diagnostic accuracy. We further validated the diagnostic value of the 4 genes and the risk score model in a clinical cohort, and the risk score can be used in the differential diagnosis of CML and other hematological malignancies. The risk score can also be used to identify molecular subtypes and predict response to imatinib treatment. These results reveal the characteristics of immunosuppression and metabolic reprogramming in CML patients, and the identification of molecular subtypes and biomarkers provides new ideas and insights for the clinical diagnosis and treatment.

Multilateral Passivation Strategy in Post-Synthetic Flexible Metal-Organic Frameworks for Enhancing Perovskite Solar Cells.

The photovoltaic performance of perovskite solar cells is severely limited by the innate defects of perovskite films. Metal-organic framework (MOF)-based additives with luxuriant skeleton structures and tailored functional groups show a huge potential to solve these problems. Here, a multilateral passivation strategy is performed by introducing two alkyl-sulfonic acid functionalized MOFs, MIL-88B-1,3-SO3H and MIL-88B-1,4-SO3H, respectively, obtained from MIL-88B-NH2 through a post-synthetic process, for coordinating the lead defects and inhibiting non-radiative recombination. The flexible MIL-88B-type frameworks endow both functionalized MOFs with excellent electrical conductivity and preferable carrier transport in the hole-transport materials. Compared with the original MIL-88B-NH2 and MIL-88B-1,4-SO3H, MIL-88B-1,3-SO3H exhibits optimal steric hindrance and multiple passivation groups (-NH2, -NH-, and -SO3H), achieving the champion doped device with an enhanced power conversion efficiency (PCE) of 22.44% and excellent stability, which maintains 92.8% of the original PCE under ambient conditions (40% humidity and 25 °C) for 1200 h.

3D chrysanthemum-like g-C3N4/TiO2 as an efficient visible-light-driven Z-scheme hybrid photocatalyst for tetracycline degradation.

Utilization of a solar-driven semiconductor as a photocatalyst to degrade antibiotic pollutants is a feasible and environmentally friendly technology. In this paper, 3D chrysanthemum-like g-C3N4/TiO2 as a visible-light-driven hybrid photocatalyst with a Z-scheme heterostructure was firstly synthesized by the in situ hydrothermal synthesis method. Experiments proved that this 3D chrysanthemum-like g-C3N4/TiO2 had better degradation performance toward tetracycline than TiO2 and g-C3N4. In particular, when optimized g-C3N4/TiO2-2 was applied for tetracycline removal (200 ml, 10 mg L-1), the corresponding degradation efficiency could reach nearly 100% within 60 min. The improved photocatalytic activity was the result of better utilization of the heterostructure-induced visible light, more efficient charge transfer in the Z-scheme heterojunction as well as stronger redox capability. The Z-scheme degradation mechanism was supported by the trapping experiments of active species and ESR radical detection, and the whole photocatalytic process was controlled by the combined action of ˙O2-, h+ and ˙OH radicals. This study may be beneficial for the design of more efficient sunlight-driven hybrid photocatalysts and their applications in wastewater treatment.

SGLT2 inhibitors can reduce the incidence of abnormal blood glucose caused by statins in non-diabetes patients with HFrEF after PCI.

BACKGROUND: Taking statins for a long time is associated with an increased risk of new-onset diabetes mellitus. Sodium-glucose cotransporter-2 (SGLT2) inhibitors can reduce insulin resistance and improve pancreatic ß-cell function. METHODS AND RESULTS: In total, 333 non-diabetes patients with heart failure with reduced ejection fraction (HFrEF) after percutaneous coronary intervention (PCI) are included. The enrolled patients are divided into a matched group (n = 198) and an SGLT2 inhibitors group (n = 135). There are no statistical differences in general information between the two groups before treatment. After a mean follow-up time of 13 months, abnormal blood glucose levels are significantly higher in the matched group than in the SGLT2 inhibitors group (6.06 vs. 0.74%, P < 0.05). There are no statistically significant differences in the alanine aminotransferase (ALT), uric acid (UA), and estimated glomerular filtration (eGFR) levels between the two groups. CONCLUSION: SGLT2 inhibitors play a significant protective role in reducing the risk of statins-induced abnormal blood glucose in non-diabetes patients with HFrEF after PCI, without increasing the burden on the heart, kidneys, and liver.

The telehealth program of occupational therapy among older people: an up-to-date scoping review.

BACKGROUND: The average life expectancy of older people is increasing, and most seniors desire to age at home and are capable of living independently. Occupational therapy (OT) is client-centered and uses patients' meaningful activities, or occupations, as treatment methods, thus playing an important role in later adulthood. Telemedicine removes the constraints of time and space, and the combination of OT and telemedicine can greatly improve medical efficiency and clinical effectiveness. AIMS: The purpose of this scoping review was to examine the scope and effectiveness of telehealth OT for older people. METHODS: This scoping review was conducted following the methodological framework proposed by Arksey and O'Malley. We searched the literature in five databases following the PICOS (Population, Intervention, Comparison, Outcome, Study design) guideline, from inception to April 2022. Two trained reviewers independently retrieved, screened, and extracted data, and used a descriptive synthesizing approach to summarize the results. RESULTS: The initial search yielded 1249 studies from databases and manual searches, of which 20 were eligible and were included in the final review. A thematic analysis revealed five main themes related to telehealth OT: occupational assessment, occupational intervention, rehabilitation counseling, caregiver support, and activity monitoring. CONCLUSIONS: Telehealth OT has been used widely for older people, focusing primarily on occupational assessment and intervention provided conveniently for occupational therapists and older clients. In addition, telehealth OT can monitor patients' activities and provide rehabilitation counseling and health education for the elderly and their caregivers, thus improving the security of their home life and the efficacy of OT. During the COVID-19 pandemic, telehealth will be an effective alternative to face-to-face modalities.

The effect of perioperative pelvic floor muscle exercise on urinary incontinence after radical prostatectomy: a meta-analysis.

BACKGROUND: Pelvic floor muscle exercise (PFME) is the most common conservative management for urinary incontinence (UI) after radical prostatectomy (RP). We performed this meta-analysis to investigate whether PFME during the entire perioperative period, including before and after RP, can significantly improve the recovery of postoperative UI. METHODS: We systematically reviewed randomized controlled trials (RCT) from PubMed, Medline, web of science, Cochrane library, and clinicalitrials.com prior to October 2022. Efficacy data were pooled and analyzed using Review Manager Version 5.3. Pooled analyses of urinary incontinence rates 1, 3, 6, and 12 months postoperatively were conducted, using odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: We included a total of 15 RCT studies involving 2178 patients received RP. Postoperative UI could be improved after 1 month, 3 months and 6 months, and the OR were 0.26 (95%CI:0.15-0.46) 0.30 (95%CI: 0.11-0.80) 0.20 (95%CI: 0.07- 0.56) in postoperative PFME group compared to no PFME group. However, there was no significant difference between the two groups in 12 months after surgery, and the OR was 0.85(95%CI: 0.48,1.51). There were similar results in perioperative PFME group compared to no PFME group with the OR of 0.35 (95%CI: 0.12, 0.98) and 0.40 (95%CI: 0.21, 0.75) in 1 and 3 months after surgery. Our results indicated no significant difference between perioperative PFME group and postoperative PFME group. The OR was 0.58 (95%CI: 0.20-1.71) 0.58 (95%CI:0.20-0.71) and 0.66 (95%CI: 0.32-1.38) in 1, 3 and 6 months after surgery. CONCLUSION: Application of PFME after RP significantly reduced the incidence of early postoperative UI, and additional preoperative PFME had no significant improvement on the recovery of UI.

Adult Child Schooling and Older Parents' Cognitive Outcomes in the Survey of Health, Aging and Retirement in Europe (SHARE): A Quasi-Experimental Study.

A growing body of research suggests that adult child educational attainment benefits older parents' cognitive outcomes via financial (e.g., direct monetary transfers) and nonfinancial (e.g., psychosocial) mechanisms. Quasi-experimental studies are needed to circumvent confounding bias. No such quasi-experimental studies have been completed in higher-income countries, where financial transfers from adult children to aging parents are rare. Using data on 8,159 adults aged ≥50 years in the Survey for Health, Aging and Retirement in Europe (2004/2005), we leveraged changes in compulsory schooling laws as quasi-experiments. Each year of increased schooling among respondents' oldest children was associated with better verbal fluency (ß = 0.07, 95% CI: 0.02, 0.12) scores; overall associations with verbal memory scores were null, with mixed and imprecise evidence of association in models stratified by parent gender. We also evaluated associations with psychosocial outcomes as potentially important mechanisms. Increased schooling among respondents' oldest children was associated with higher quality-of-life scores and fewer depressive symptoms. Our findings present modest albeit inconsistent evidence that increases in schooling may have an "upward" influence on older parents' cognitive performance even in settings where financial transfers from adult children to their parents are uncommon. Associations with parents' psychosocial outcomes were more robust.

Smart MOF-on-MOF Hydrogel as a Simple Rod-shaped Core for Visual Detection and Effective Removal of Pesticides.

The immoderate use of pesticides in the modern agricultural industry has led to the pollution of water resources and ultimately threatens the human body. Herein, two metal-organic frameworks (MOFs), namely {[Zn(tpt)2 ·2H2 O]}n (Zn1) and {[Zn2 (tpt)2 (bdc)]}n (Zn2), (Htpt = 5-[4(1H-1,2,4-triazol-1-yl)]phenyl-2H-tetrazole), respectively, are constructed as smart materials for visual and on-site detection of pesticides and their removal from water. The exposed nitrogen-rich sites and high chemical stability make Zn2 a self-assembly core to further fabricate MOF-on-MOF-sodium alginate (ZIF-8-on-Zn2@SA) composite by wrapping ZIF-8 on the outside surface. Inheriting the excellent fluorescent emission of Zn2, the rod-like ZIF-8-on-Zn2@SA module exhibits naked-eye detection of thiophanate-methyl (TM) in real fruits and vegetables with a broad linear range (10-100 × 10-6  m), a low limit of detection (LOD = 0.14 × 10-6  m), and satisfactory recoveries (98.30-102.70%). In addition, carbendazim (CBZ), the metabolite of TM after usage in crops, can be efficiently removed from water by the ZIF-8-on-Zn2@SA (qmax  = 161.8 mg g-1 ) with a high correlation coefficient (R2  > 0.99). Therefore, the portable ZIF-8-on-Zn2@SA sensing platform presents a promising candidate for monitoring and removal of pesticides, especially suitable for regions with serious pesticide environmental pollution.

The Relationship Between Pain and Psychological Distress During the COVID-19 Pandemic: Is Social Technology Use Protective?

OBJECTIVES: The COVID-19 pandemic and resulting shelter-in-place orders have profoundly changed the everyday social environment. This study examines the relationship between pain and psychological distress (depression, anxiety, and loneliness) among U.S. adults ages 54 and older during the pandemic. We also test whether use of technology for social purposes moderates the association between pain severity and psychological distress. METHODS: Using cross-sectional data on 1,014 adults ages 54 and older (pain free, n = 637; mild pain, n = 106; moderate pain, n = 227; and severe pain, n = 64) from the 2020 Health and Retirement Study COVID-19 Project (Early, Version 1.0), we conducted regression analyses to test the association between pain severity and psychological outcomes and to assess social technology use frequency as a moderator. RESULTS: Compared with their pain-free peers, participants with mild-to-moderate pain reported more depressive symptoms and greater loneliness; those with severe pain reported higher levels of depression, anxiety, and loneliness. Social technology use was associated with lower levels of depression and loneliness. However, interaction analyses show that social technology use predicted an increase in depression for individuals with pain but a decrease in depression among pain-free individuals. For anxiety and loneliness, no significant effects of social technology use were observed. CONCLUSION: Older adults with pain are at high risk of depression, anxiety, and loneliness during the pandemic. Although social technologies have become a common alternative to face-to-face interactions during the COVID-19 crisis, and overall they can provide mental health benefits, our results suggest that social technologies can be detrimental to psychological well-being among people with pain. These findings can inform technology-based interventions aiming to promote well-being among older adults with pain.

Prognostic significance of visit-to-visit variability, and maximum and minimum LDL cholesterol in diabetes mellitus.

BACKGROUND: Current guidelines for dyslipidemia management recommend that the LDL-C goal be lower than 70 mg/dL. The present study investigated the prognostic significance of visit-to-visit variability in LDL-C, and minimum and maximum LDL-C during follow-up in diabetes mellitus. METHODS: The risk of outcomes in relation to visit-to-visit LDL-C variability was investigated in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial. LDL-C variability indices were coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV). Multivariable Cox proportional hazards models were employed to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Compared with the placebo group (n=2667), the fenofibrate therapy group (n=2673) had a significantly (P<0.01) lower mean plasma triglyceride (152.5 vs. 178.6 mg/dL), and total cholesterol (158.3 vs.162.9 mg/dL) but a similar mean LDL-C during follow-up (88.2 vs. 88.6 mg/dL, P>0.05). All three variability indices were associated with primary outcome, total mortality and cardiovascular mortality both in the total population and in the fenofibrate therapy group but only with primary outcome in the placebo group. The minimum LDL-C but not the maximum during follow-up was significantly associated with various outcomes in the total population, fenofibrate therapy and placebo group. The minimum LDL-C during follow-up ≥70 mg/dL was associated with an increased risk for various outcomes. CONCLUSIONS: Visit-to-visit variability in LDL-C was a strong predictor of outcomes, independent of mean LDL-C. Patients with LDL-C controlled to less than 70 mg/dL during follow-up might have a benign prognosis. ClinicalTrials.gov number: NCT00000620.

Effect of the Early Application of Evolocumab on Blood Lipid Profile and Cardiovascular Prognosis in Patients with Extremely High-Risk Acute Coronary Syndrome.

Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors significantly reduce low-density lipoprotein cholesterol (LDL-C) and improve the prognosis of patients with acute coronary syndrome (ACS). However, the feasibility and safety of early application of PCSK9 inhibitors on the basis of statins combined with ezetimibe to strengthen lipid lowering in extremely high-risk coronary heart disease populations are still unknown.This study was a prospective, randomized controlled study. A total of 136 patients with extremely high-risk ACS with LDL-C ≥ 3.0 mmol/L after percutaneous coronary intervention (PCI) treatment were randomly assigned 1:1 to the control group (atorvastatin 40 mg/day and ezetimibe 10 mg/day) or the evolocumab group (evolocumab 140 mg every 2 weeks combined with atorvastatin 40 mg/day and ezetimibe 10 mg/day). We compared the blood lipid profiles, major adverse cardiovascular events (MACEs), and adverse reactions. MACEs included cardiogenic death, nonfatal myocardial infarction, nonfatal stroke, and readmission due to angina. Adverse reactions included allergies, myalgia, poor blood glucose control, and liver damage.Within 1 month, the average level of LDL-C in the evolocumab group decreased from 3.54 to 0.57 mmol/L and that in the control group decreased from 3.52 to 1.26 mmol/L. The LDL-C compliance (< 1.0 mmol/L) rate was significantly increased in the evolocumab group compared with the control group (82.35% versus 22.06%, P < 0.01). The average level of lipoprotein (a) (Lp (a) ) in the control group increased by 9.94 ± 51.93% from baseline after treatment, but evolocumab reduced the Lp (a) level (-38.84 ± 32.40%). Additionally, evolocumab further reduced the levels of apolipoprotein B/A1 (-70.56 ± 22.38% versus -51.29 ± 18.14%), cholesterol (-54.76 ± 18.10% versus -41.16 ± 18.14%), and apolipoprotein B (-66.47 ± 26.89% versus -46.78 ± 24.12%) compared with those in the control group, all P < 0.01. The blood lipid levels of both control and evolocumab groups stabilized after 1 month. During the 3-month follow-up, the incidence of MACEs after PCI was lower in the evolocumab group than in the control group (8.82% versus 24.59%, P = 0.015), and evolocumab combined with statins and ezetimibe did not increase the occurrence of adverse reactions (13.24% versus 11.48%, P = 0.762).In patients with extremely high-risk ACS with high levels of LDL-C, adding evolocumab to their treatment regimen as early as possible may enhance lipid lowering, increase the patient's LDL-C compliance rate in the short term, and improve cardiovascular prognosis but will not increase adverse reactions.

Structural Design of Low Toxicity Metal-Organic Frameworks for Multifunction Detection of Organic and Inorganic Contaminants from Water.

Metal-organic frameworks (MOFs)-based sensors for monitoring toxic substances in wastewater have attracted great attention due to the efficient and reliable performance. Here, we has synthesized two novel zinc-based MOFs [Zn(ttb)2(H2O)2]n (Zn1-ttb) and {[Zn(ttb)2]·0.5CH3CN}n (Zn2-ttb) through changing the polarity of reaction solvents and finally obtained target 2D MOF material [Zn(ttb)(bdc)0.5]n(Zn3-ttb-bdc) by successfully introducing an ancillary ligand H2bdc (Httb = 1-(triazo-1-ly)-4-(tetrazol-5-ylmethyl)benzene, H2bdc = 1,4-benzenedicarboxylic acid). As-prepared Zn3-ttb-bdc exhibits high water and chemical stability as well as excellent fluorescence property. Due to the -COOH binding sites from H2bdc, Zn3-ttb-bdc shows high sensitivity and a rapid luminescent response to a representative organic micropollutant trinitrophenol (TNP) and inorganic pollutants (Fe3+ and Cr2O72-) in wastewater. The mechanisms of multifunctional detection abilities of Zn3-ttb-bdc toward different types of pollutants are further studied. This work presents the structural design in preparing MOF materials for multifunctional detection performance, thus opening new perspectives for emerging MOF-based sensors as environmental monitors.

Association between halitosis and female fecundability in China: a prospective cohort study.

BACKGROUND: Periodontal diseases and poor oral hygiene are potentially associated with decreased female fecundability. Fecundability refers to the probability of conception during a given period measured in months or menstrual cycles. This study aims to examine whether halitosis is associated with female fecundability in a large sample of Chinese women who planned to be pregnant. METHODS: In 2012, a total of 6319 couples came for preconception care in eight districts in Shanghai, China and were followed by telephone contact. Three thousand nine hundred fifteen women who continued trying to be pregnant for up to 24 months remained for final statistical analyses. Halitosis was self-reported at the preconception care visit. Time to pregnancy (TTP) was reported in months and was censored at 24 months. Fecundability ratio (FR) was defined as the ratio of probability of conception among those with and without halitosis. FR and 95% confidence interval (CI) were estimated using the discrete-time Cox model. RESULTS: 80.1 and 86.1% of women had self-reported clinically confirmed pregnancy within 12 and 24 months, respectively. Halitosis was reported in 8.7% of the women. After controlling for potential confounders, halitosis was associated with a reduced probability of spontaneous conception (for an observation period of 12 months: adjusted FR 0.82, 95% CI 0.72-0.94; for an observation period of 24 months: adjusted FR 0.84, 95% CI 0.74-0.96). CONCLUSIONS: Halitosis is associated with reduced fecundability in Chinese women.