Robust High-performance Bifunctional Porous Cobalt MOF-Based Catalysts for Overall Water Splitting.

MOF-based materials, as bifunctional catalysts for electrocatalytic water splitting, play an important role in the application and development of clean fuel hydrogen energy. This study presents a series of novel 3D Co-based MOFs with layered networks, including [Co(4,4'-bipy)0.5(aip)(CH3OH)·H2O]n (Co-MOF 1), [Co2(1,3'-bit)(aip)2(CH3OH)·H2O]n (Co-MOF 2), [Co(4,4'-bipb)(aip)]n (Co-MOF 3), and [Co2(4,4'-bipe)(aip)2·1.5H2O]n (Co-MOF 4). Their single-crystal structures of Co-MOFs 1-4 are characterized and analyzed before being applied in alkaline solutions for water decomposition (OER and HER). The electrocatalytic tests indicate that Co-MOFs 1-4 exhibit a good performance. Notably, Co-MOF 4 exhibits great behavior which has low overpotentials of 94 and 188 mV (OER) as well as 185 and 352 mV (HER) at the currents of 10 and 100 mA cm-2, respectively. In comparison with Co-MOFs 1-3, Co-MOF 4 has the lowest Tafel slopes, highest ECSA, and smallest resistance. The immanent qualities, such as distinct interwoven long chain layered structure, unsaturated coordination modes, and synergistic catalytic qualities among Co ions, contribute to explaining the results. The fundamentals provide valuable information for the investigation of innovative MOF-based bifunctional electrocatalysts for overall water splitting.

Pillar-Layered Porous Metal-Organic Frameworks with Co2N2O8 Clusters and Tetragonal Ligands for CO2 Conversion.

Converting CO2 to valuable chemicals and fuels is a viable method to establish a carbon-neutral energy cycle in the environment. Metal-organic frameworks (MOFs), characterized by dispersed active sites, high porosity, etc., have displayed a great application prospect in the electrochemical/chemical CO2 reduction reaction (CO2RR) process. Herein, we proposed a one-step production to establish a series of pillar-layered porous MOFs, [Co2(L)(bimb)]n (MOF 1) and [Co4(L)2(bidpe)2]n (MOF 2) [H4L = 5'-(4-carboxyphenyl)-(1,1':2',1″-terphenyl)-4,4',4″-tricarboxylic, bimb = 1,4-bis(imidazol-1-yl)-butane, bidpe = 4'-bis(imidazolyl) diphenyl ether], for preferential conversion of CO2 via ligand adjustment and increase of active sites' density. According to single-crystal X-ray diffraction studies, [Co2(L)(bimb)]n exhibits pillar-layered binuclear 3D frameworks with a 2,4,6-linked 3-nodes new topology structure, while [Co4(L)2(bidpe)2]n displays pillar-layered tetranuclear interspersed networks with a 4,6-linked 2-nodes fsc topology structure through a ligand adjustment strategy. Meanwhile, the pillar-layered structure of the MOFs with abundant active sites is conducive to mass diffusion and benefits the conversion of CO2. MOFs 1-2 exhibit good electrocatalytic activity for CO2RR in 0.5 M KHCO3 solution. Especially, the current density of MOF 2 generated at -0.90 V (vs. RHE) reaches -81.6 mA·cm-2, which is 3.1 times higher than that under an Ar atmosphere. In addition, MOFs 1-2 can be used as a heterogeneous catalyst for chemical conversion of CO2. The results are expected to provide inspiration for rational design to develop stable and high-efficiency MOF-based electrocatalysts for CO2RR.

Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis.

Cholesterol biosynthetic intermediates, such as lanosterol and desmosterol, are emergent immune regulators of macrophages in response to inflammatory stimuli or lipid overloading, respectively. However, the participation of these sterols in regulating macrophage functions in the physiological context of atherosclerosis, an inflammatory disease driven by the accumulation of cholesterol-laden macrophages in the artery wall, has remained elusive. Here, we report that desmosterol, the most abundant cholesterol biosynthetic intermediate in human coronary artery lesions, plays an essential role during atherogenesis, serving as a key molecule integrating cholesterol homeostasis and immune responses in macrophages. Depletion of desmosterol in myeloid cells by overexpression of 3ß-hydroxysterol Δ24-reductase (DHCR24), the enzyme that catalyzes conversion of desmosterol to cholesterol, promotes the progression of atherosclerosis. Single-cell transcriptomics in isolated CD45+CD11b+ cells from atherosclerotic plaques demonstrate that depletion of desmosterol increases interferon responses and attenuates the expression of antiinflammatory macrophage markers. Lipidomic and transcriptomic analysis of in vivo macrophage foam cells demonstrate that desmosterol is a major endogenous liver X receptor (LXR) ligand involved in LXR/retinoid X receptor (RXR) activation and thus macrophage foam cell formation. Decreased desmosterol accumulation in mitochondria promotes macrophage mitochondrial reactive oxygen species production and NLR family pyrin domain containing 3 (NLRP3)-dependent inflammasome activation. Deficiency of NLRP3 or apoptosis-associated speck-like protein containing a CARD (ASC) rescues the increased inflammasome activity and atherogenesis observed in desmosterol-depleted macrophages. Altogether, these findings underscore the critical function of desmosterol in the atherosclerotic plaque to dampen inflammation by integrating with macrophage cholesterol metabolism and inflammatory activation and protecting from disease progression.

Genetic dissection of the impact of lncRNA AI662270 during the development of atherosclerosis.

BACKGROUND: Atherosclerosis is driven by synergistic interactions between pathological biomechanical and lipid metabolic factors. Long noncoding RNAs (LncRNAs) have been implicated in atherogenesis. The purpose of this study was to investigate the potential mechanism of lncRNA AI662270 on macrophage cholesterol transport in atherosclerosis. METHODS: Apolipoprotein E deficiency (ApoE-/-) mice were fed a high fat diet for 16 weeks to construct atherosclerotic model, and the mice were injected with recombinant lentivirus carrying AI662270 gene to overexpress AI662270. Macrophages were cleared by liposomal clondronate in vivo. Fundamental experiments and functional assays, hematoxylin and eosin staining, oil red O staining and others, were performed to evaluate the function of AI662270 on atherogenesis. Peritoneal macrophages were treated with oxidized low density lipoprotein (ox-LDL) to simulate in vitro model. Mechanism assays, RNA-interacting protein immunoprecipitation, RNA-protein pulldown and others, were performed to study the regulatory mechanism of AI662270 in macrophages. RESULTS: The novel AI662270 was mainly enriched in macrophages, but not in endothelial cells, smooth muscle cells and fibroblasts of mouse atherosclerotic lesions and was upregulated by ox-LDL. Overexpression of AI662270 resulted in lipid accumulation, larger atherosclerotic plaques and cardiac dysfunction in vivo. After macrophages were removed, the pro-atherogenic effect of AI662270 disappeared. Downregulation of AI662270 in macrophages protected against foam cell formation by potentiating cholesterol efflux and reducing intracellular total cholesterol. The opposite effect was observed in macrophage-specific AI662270-overexpressed cells in vitro. AI662270 bound to adenosine triphosphate-binding cassette transporter A1 (Abca1) responsible for regulating cholesterol efflux in macrophages. Forced expression of AI662270 in macrophages decreased Abca1 expression. The reverse occurred when expression of AI662270 was repressed. CONCLUSION: These findings reveal an essential role for AI662270 in atherosclerosis progression by regulating cholesterol efflux from macrophages.

Prostate Health Index Density Outperforms Prostate-specific Antigen Density in the Diagnosis of Clinically Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging of the Prostate: A Multicenter Evaluation.

PURPOSE: We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy. MATERIALS AND METHODS: This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer). RESULTS: A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively. CONCLUSIONS: Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.

Designed Construction of 2D Honeycomb Cationic MOF Materials for Selective Removal of Sulfonic Anionic Dyes.

Various carcinogenic dyes in water bodies are difficult to degrade due to their stability to light and oxidants, causing extended pollution. In this study, MOF 1 ({[Co(tib)2]·(H2O)2·SO4}n) and MOF 2 ({[Cu(tib)2]·(H2O)2·SO4}n) (tib = 1,3,5-tirs(1-imidazolyl)benzene) were synthesized by the solvothermal method. MOFs 1 and 2 were successfully characterized by single-crystal X-ray diffraction (XRD) and powder X-ray diffraction (PXRD). Based on the structural characteristics of MOFs 1 and 2, we designed two cationic MOF material skeletons, namely, MOFs I and II ([Co(tib)22+]n and [Cu(tib)22+]n), which were obtained by calcination in combination with the thermogravimetric curve to remove the free components in the lattice. As expected, MOFs I and II showed an excellent adsorption effect on sulfonic anionic dyes. Notably, the adsorption capacity of MOF I can reach 2922.8 mg g-1 for Congo Red (CR) at room temperature (RT). The adsorption process fits the pseudo-second-order kinetic model and Freundlich isotherm model. Moreover, zeta potential tests and quantum chemical calculations indicate that electrostatic interactions and hydrogen bond between the hydroxyl group on the sulfonic acid group and the N atom on the imidazole ring mainly promote the adsorption of CR dyes on MOF I. MOFs I and II are revealed as a promising novel adsorption material to remove hazardous organic aromatic pollutants with high efficiency in future endeavors.

Influence of preoperative body mass index on prognosis for patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: The impact of body mass index (BMI) on patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) is controversial. Increasing evidence suggests an age-dependent relationship between obesity and outcomes for some solid organ tumors. Herein, we aimed to assess the prognostic value of preoperative BMI in UTUC patients treated with RNU in Taiwan. METHODS: This was a retrospective single-center study of 468 UTUC patients undergoing RNU during January 2010-December 2017, with preoperative BMI classification and subgroup analysis based on ages of < or ≥ 70 years. All UTUC patients underwent RNU and bladder cuff excision. Overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were analyzed. Fisher's exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model were used for data analysis. RESULTS: The median follow-up duration was 36 months. Patients with higher versus lower BMI (cutoff: 25 kg/m2) showed no differences in OS; older patients had poor OS (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.24-2.40; p < 0.001). Older age was an independent predictor of poor OS in multivariate Cox regression analysis (p = 0.001). Younger patients with higher BMI (p = 0.02) had better DFS than older patients with no BMI-related survival differences. Higher BMI was an independent predictor of favorable DFS in younger patients in multivariate Cox regression analysis (HR, 0.53; 95% CI 0.28-0.99; p = 0.043). CONCLUSION: Younger UTUC patients with higher BMI were independently associated with a favorable DFS.

Three-Dimensional Cadmium-Organic Framework with Dual Functions of Oxygen Evolution in Water Splitting and Fenton-like Photocatalytic Removal of Organic Pollutants.

Metal-organic frameworks (MOFs) have exhibited appreciable potential as catalytic agents in the field of material science. The research of new MOFs with dual functions in electrocatalysis and photocatalysis under ultraviolet (UV) irradiation is extremely pivotal for renewable energy applications. Hence, we synthesized a series of three-dimensional MOFs, namely, [Cd(bimb)2(HITA)2]n (Cd-MOF 1), {[Cd(bimb)6](NO3)2}n (Cd-MOF 2), and [Cd(bimb)4(ONO2)2]n (Cd-MOF 3) (bimb = 1,4-bis(imidazol-1-ylmethyl)benzene; H2ITA = 5-hydroxyisophthalic acid), with applicability in the oxygen evolution reaction process and Fenton-like photocatalysis. The obtained results show that Cd-MOF 1 exhibited the most remarkable catalytic performance, affording a current density of 10 mA cm-2 at a very low overpotential of 279 mV and the smallest Tafel slope of 85.13 mV dec-1. Meanwhile, these MOFs can generate hydroxyl radicals (•OH) under UV light irradiation with the existence of H2O2, enabling the rapid degradation of organic pollutants. This study provides a valuable direction for producing multifunctional and environmentally friendly catalysts.

Nurses' Willingness and Demand for Internet+Home Care Services and the Associated Factors in Municipal Hospitals in China: Cross-Sectional Survey.

BACKGROUND: Developing Internet+home care (IHC) services is a promising way to address the problems related to population aging, which is an important global issue. However, IHC services are in their infancy in China. Limited studies have investigated the willingness and demand of nurses in municipal hospitals to provide IHC services. OBJECTIVE: This study aims to investigate the willingness and demand of nurses in municipal hospitals in China to provide IHC services and analyze the factors to promote IHC development in China. METHODS: This cross-sectional study used multistage sampling to recruit 9405 nurses from 10 hospitals in 5 regions of China. A self-designed questionnaire with good reliability and validity was used to measure nurses' willingness and demand for providing IHC services. Data analysis used the chi-square test, Welch t test, binary logistic regression analysis, and multiple linear regression analysis. RESULTS: Nurses were highly willing to provide IHC services and preferred service distances of <5 km and times from 8 AM to 6 PM. An individual share >60% was the expected service pay sharing. Job title, educational level, monthly income, and marital status were associated with nurses' willingness to provide IHC services in binary logistic regression analysis. Supervising nurses were 1.177 times more likely to express a willingness to provide IHC services than senior nurses. Nurses with a bachelor's degree had a 1.167 times higher likelihood of expressing willingness to provide IHC services than those with a junior college education or lower. Married nurses were 1.075 times more likely to express a willingness than unmarried nurses. A monthly income >¥10,000 increased the likelihood of nurses' willingness to provide IHC services, by 1.187 times, compared with an income <¥5000. Nurses' total mean demand score for IHC services was 17.38 (SD 3.67), with the highest demand being privacy protection. Multiple linear regression analysis showed that job title, monthly income, and educational level were associated with nurses' demand for IHC services. Supervising nurses (B=1.058, P<.001) and co-chief nurses or those with higher positions (B=2.574, P<.001) reported higher demand scores than senior nurses. Monthly incomes of ¥5000 to ¥10,000 (B=0.894, P<.001) and >¥10,000 (B=1.335, P<.001), as well as a bachelor's degree (B=0.484, P=.002) and at least a master's degree (B=1.224, P=.02), were associated with higher demand scores compared with a monthly income <¥5000 and junior college education or lower, respectively. CONCLUSIONS: Nurses in municipal hospitals showed a high willingness and demand to provide IHC services, with differences in willingness and demand by demographic characteristics. Accordingly, government and hospitals should regulate the service period, service distance, and other characteristics according to nurses' willingness and demand and establish relevant laws and regulations to ensure the steady and orderly development of IHC services.

Type D Personality Independently Predicts Erectile Dysfunction in Taiwanese Young Men.

BACKGROUND: Studies have demonstrated that erectile dysfunction has a well-established bidirectional relationship with depression and have indicated an independent association of type D personality (TDP) with depression. Nevertheless, the relationship of erectile dysfunction with TDP has not been sufficiently examined. AIM: To examine the associations among depression symptoms, TDP, and erectile dysfunction. METHODS: The cross-sectional study recruited 1740 sexually active Taiwanese men (age: 20-40 years) with erectile dysfunction. Participants completed an online questionnaire collecting general demographic information and containing the International Index of Erectile Function-5, Type D Scale-14, and Depression and Somatic Symptom Scale. Pearson's chi squared or Student's t'test was conducted for comparisons between participants with vs without TDP. We conducted multivariate and univariate logistic regression analysis to investigate the predictors of moderate/severe erectile dysfunction. OUTCOMES: The prevalence of TDP and moderate/severe erectile dysfunction, the associations between TDP and the severities of depression symptoms and erectile dysfunction, and independent risk factors for moderate/severe erectile dysfunction. RESULTS: A total of 360 (15.9%) and 941 (54.08%) men had moderate/severe erectile dysfunction and TDP, respectively. Men with TDP reported significantly higher total and subscale scores in the International Index of Erectile Function-5 and the Depression and Somatic Symptom Scale; this group also exhibited higher prevalence of moderate or severe erectile dysfunction. According to the univariate analysis, all variables significantly predicted moderate or severe erectile dysfunction except for age and body mass index. A multivariate analysis revealed TDP status and depression symptoms to be independent predictors of moderate or severe erectile dysfunction. With regard to subscales of the Type D Scale-14, we discovered that social inhibition had a greater influence on moderate or severe erectile dysfunction than had negative affectivity. A mediation analysis indicated that the relationship between TDP and erectile dysfunction was mediated by depressive symptoms. CLINICAL IMPLICATIONS: Research has suggested that compared with the general population, individuals with TDP are less willing to seek medical consultation, have lower medication adherence, and have heightened risk of depression; urologists should strive to identify patients with TDP. STRENGTHS & LIMITATIONS: This study is the first to investigate the association of TDP with erectile dysfunction in a large population of young men by using validated instruments. Conclusions on causality cannot be drawn due to the study's cross-sectional nature. CONCLUSION: This research revealed relationships among TDP, depression symptoms, and erectile dysfunction in Taiwanese young men. Fan Y-H, Liou Y-J, Cheng W-M. Type D Personality Independently Predicts Erectile Dysfunction in Taiwanese Young Men. J Sex Med 2022;19:1397-1403.

Association between periodic limb movements during sleep and neuroimaging features of cerebral small vessel disease: A preliminary cross-sectional study.

Evidence on the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease is lacking. This study aimed to assess the association between the PLMS index and the neuroimaging features of cerebral small vessel disease on magnetic resonance imaging. Consecutive patients diagnosed with cerebral small vessel disease were enrolled. Data on the clinical characteristics, polysomnography, and brain magnetic resonance imaging were collected. The Accubrain software was used to calculate automatically the volume of white matter hyperintensities, the number of lacunar infarctions, and cerebral microbleeds. The severity of white matter hyperintensities, enlarged basal ganglia perivascular spaces, and the total cerebral small vessel disease scores were also rated visually using semiquantitative scales. The severity of PLMS was measured using the PLMS index, and the patients were divided into two groups using an established cut-off value of ≥15 per hour. Logistic regression was used to examine the association between PLMS and the neuroimaging features of cerebral small vessel disease. In total, 37 patients were included in the final analyses. The mean age was 66.49 ± 11.31 years, and 73.0% were males. The mean PLMS index was 19.30 ± 10.18. In univariate analyses, it was found that patients with cerebral small vessel disease with a PLMS index ≥15 had increased enlarged basal ganglia perivascular spaces (OR 6.136, 95%CI 1.101-34.214) and increased total cerebral small vessel disease scores (OR 6.0, 95%CI 1.253-28.742). Only the association between the PLMS index and the total cerebral small vessel disease burden score remained statistically significant after adjusting for age, sex, and the presence of moderate to severe obstructive sleep apnea syndrome. In conclusion, an elevated PLMS index is likely to be associated with a greater cerebral small vessel disease burden. PLMS might be a novel potential marker of cerebral small vessel disease.

Prevalence of lower urinary tract symptoms in children with early-treated infantile-onset Pompe disease: A single-centre cross-sectional study.

AIM: To evaluate lower urinary tract symptoms (LUTS) in children with infantile-onset Pompe disease (IOPD) who received early treatment. METHODS: Pompe disease (PD), or glycogen storage disease II is a rare autosomal recessive lysosomal storage disease that affects multiple organ systems. To our knowledge, only one study has focused on the relationship between LUTS and incontinence in children with PD. This cross-sectional study was conducted from August 2019 through March 2021 and children with IOPD, who had received early and regular enzyme replacement therapy, were enrolled. Participants or their parents completed the Dysfunctional Voiding Scoring System (DVSS) questionnaire. All children underwent uroflowmetry and postvoid residual urine measurements. Fourteen children (age, 4-9 years) with IOPD were enrolled. RESULTS: Ten patients (71.4%) had abnormal uroflow curves. In addition, results of the DVSS revealed that approximately half (42.9%) of our IOPD patients had voiding dysfunction, with urinary incontinence as the most common symptom (64.3%, 9/14). No significant correlations were found between LUTS and uroflow curves in children with IOPD. CONCLUSIONS: The frequency of LUTS and lower urinary tract dysfunction noted on uroflowmetry should encourage pediatricians to actively identify IOPD patients with LUTS, regardless of the timing and frequency of their treatments, and refer them to a urologist for further evaluation and appropriate treatment.

Efficacy of intravenous hydration during extracorporeal shock wave lithotripsy in improving ureteral stone treatment success rate.

OBJECTIVE: The treatment efficacy of extracorporeal shock wave lithotripsy for urolithiasis depends on several factors. We aimed to evaluate the impact of intravenous hydration during shock wave lithotripsy on stone treatment success rate in patients with ureteral stones. METHODS: We retrospectively evaluated patients with ureteral stones <2 cm in diameter treated with extracorporeal shock wave lithotripsy at two sites. Patients from one of the sites received intravenous hydration with 500 mL of 0.9% NaCl. Stone treatment success status was defined as stone-free or residual ureteral stones <0.4 cm in diameter 1 month after the procedure. Predictive factors associated with treatment success were evaluated using univariate and multivariate logistic regression. RESULTS: Overall, 146 consecutive patients with ureteral stones were included. Eighty (54.8%) patients received intravenous hydration. The overall stone treatment success rate was 66.4%. Those with intravenous hydration during the shock wave lithotripsy had significantly smaller stone size, lower serum creatinine levels, lower rate of alpha-blockers use, and higher rate of nonsteroidal anti-inflammatory drug use. Upon multivariate analysis, stone treatment success status postprocedure was significantly associated with stone size (odds ratio 4.118, 95% confidence interval 1.920-8.832, P < 0.0001) and intravenous hydration during the procedure (odds ratio 2.475, 95% confidence interval 1.176-5.208, P = 0.017). CONCLUSION: Besides small ureteral stone size, concomitant intravenous hydration with 500 mL of normal saline during extracorporeal shock wave lithotripsy was significantly associated with subsequent stone passage. Administering 0.9% NaCl may be a simple and effective measure to improve the treatment efficacy of extracorporeal shock wave lithotripsy.

R558C NOTCH3 Mutation in a CADASIL Patient with Intracerebral Hemorrhage: A Case Report with Literature Review.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic cerebral small-vessel disease, which is characterized by migraine, recurrent ischemic strokes, psychiatric disorder, progressive cognitive decline, and occasionally intracerebral hemorrhage (ICH). ICH events have been reported in a high proportion of East Asian CADASIL patients with R544C mutation in exon 11 of NOTCH3; however, whether any other specific NOTCH3 mutation determines the ICH phenotype has yet to be explored. CASE PRESENTATION: We report the case of a 60-year-old male CADASIL patient with a novel R558C mutation in exon 11 of the NOTCH3 gene, who presented with ICH in the basal ganglia and cerebellum. Brain imaging revealed multiple confluent white matter hyperintensities and abundant cerebral microbleeds (CMBs) in the bilateral basal ganglia, thalamus, and cerebellum. The patient had been having recurrent ischemic strokes prior to this ICH event, and had taken antiplatelet and antihypertensive agents for six months. We analyzed the possible reasons for ICH onset in the patient to recommend certain guidelines for the clinic. CONCLUSIONS: Novel R558C mutation-related CADASIL vasculopathy and numerous CMBs, uncontrolled hypertension, and antiplatelet therapy could collectively contribute to ICH onset in the patient with CADASIL. These findings suggest that a diagnosis of CADASIL should also be considered when patients present with ICH, whenever MRI imaging reveals typical white matter abnormalities. Furthermore, this case report emphasizes the importance of CMB assessment, appropriate blood pressure control, and cautious assessment of the risk-benefits of antiplatelet medication in patients with CADASIL.

The genomic architectures of tumour-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is characterised by a dismal prognosis; nonetheless, limited studies have unveiled the mechanisms underlying HNSCC relapse. METHODS: Next-generation sequencing was performed to identify the somatic mutations in 188 matched samples, including primary tumours, tumour-adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. The evolutionary relationship between TATs and tumours were analysed. The dynamic changes of tumour- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis. RESULTS: Alterations were detected in 27 out of 27 and 19 out of 26 tumours and TATs, respectively. TP53 was the most prevalently mutated gene in TATs. Some TATs shared mutations with primary tumours, while some other TATs were evolutionarily unrelated to tumours. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and are indicative of worse survival (hazard ratio = 14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies and were indicative of disease relapse. CONCLUSIONS: TATs might undergo the processes of premalignant transformation, tumorigenesis and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where the tumour originated or gaining private mutations independent of primary tumours. Detection of tumour- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.

Two biologically inspired tetranuclear nickel(II) catalysts: effect of the geometry of Ni4 core on electrocatalytic water oxidation.

Two biologically inspired tetranuclear nickel complexes [Ni4(L-H)4(CH3COO)3]·Cl (1) and [Ni4(L-H)4(CH3COO)4]·2CH3OH (2) (L = di(pyridin-2-yl)methanediol) have been synthesized and investigated by a combination of X-ray crystallography, PXRD, electrochemistry, in-situ UV-Vis spectroelectrochemistry and DLS. Both of the two complexes feature a core composed of four Ni(II) ions with the same peripheral ligation provided by the anionic di(pyridin-2-yl)methanediol and MeCOO- ligands. Whereas, complex 1 possesses one distorted cubane-like [Ni4(µ3-O)4] core, while 2 has one extended butterfly-like [Ni4(µ3-O)2] core. The homogeneous electrocatalytic reactivity of the two water-soluble complexes for water oxidation have been thoroughly studied, which demonstrates that both of them can efficiently electrocatalyze water oxidation with high stability under alkaline conditions, at relatively low over-potentials (η) of 420-790 mV for 1 and 390-780 mV for 2, both in the pH range of 7.67-12.32, with the high TOF of about 139 s-1 (1) and 69 s-1 (2) at pH = 12.32, respectively. By a series of comparative experiments for complexes 1 and 2, we proposed that their crystal geometries play an important role in their electrocatalytic reactivity for water oxidation. We verified that biomimetic cubane geometry could promote OER catalysis with two very similar compounds for the first time. Compared with 2, the biomimetic cubane topology of 1 could promote OER catalysis by facilitating efficient charge delocalization and electron-transfer.

Highly Stable Acid-Induced Emission-Enhancing Cd-MOFs: Synthesis, Characterization, and Detection of Glutamic Acid in Water and Fe Ions in Acid.

Two novel 3D fluorescent metal-organic frameworks (MOFs), [Cd(L)(bbibp)]n (1) and [Cd(L)(bbibp)0.5]n (2), where H2L = 4,4'-(4,4'-bipyridine-2,6-diyl)dibenzoic acid and bbibp = 4,4'-bis(benzoimidaz-1-yl)biphenyl, were acquired through a conventional method and characterized via IR spectra, single-crystal X-ray diffraction, elemental analysis, thermogravimetric analysis, powder X-ray diffraction (PXRD), scanning electron microscopy, N2 adsorption-desorption isotherms, and X-ray photoelectron spectroscopy (XPS). The crystal framework of Cd-MOF 1 remained stable in the range of pH = 1.0-12.0. Interestingly, the emission peak of 1 showed a red shift and exhibited a fluorescence turn-on effect in an acidic environment. X-ray diffraction measurement revealed that the crystal structure of 1 remained unchanged after immersion in a pH = 1.0 solution. In addition, Cd-MOFs 1 and 2 displayed fluorescent quenching to l-glutamic acid with high sensitivity and selectivity. Meanwhile, 1 showed high selectivity in recognizing Fe3+ under acidic conditions, which made 1 capable of detecting Fe3+ in acidic industrial wastewater. Finally, the fluorescent sensing mechanism was carefully studied by PXRD, transient fluorescence lifetime, XPS, and UV spectroscopy.

Patients with preoperative asymptomatic pyuria are not prone to develop febrile urinary tract infection after ureteroscopic lithotripsy.

BACKGROUND: This study aimed to evaluate the association of asymptomatic pyuria before ureterorenoscopic lithotripsy (URSL) with postoperative febrile urinary tract infection (UTI). METHODS: This observational case-control study identified the patients undergoing URSL for ureteral stones between May 2011 and October 2015. The included patients were classified into two groups: the asymptomatic pyuria group (6-50 white blood cells [WBCs]/high-power field [HPF]) and the non-pyuria group (≤ 5 WBCs/HPF). All data were collected by reviewing medical records. Postoperative outcomes were collected in terms of febrile UTI, emergency visits, and stone-free rate. RESULTS: A total of 232 patients were included, 101 in the pyuria group, 131 in the non-pyuria group. Two (0.9%) patients developed febrile UTI after URSL and 12 (5.2%) patients visited emergency department for URSL-related symptoms. The overall stone-free rate was 90.9%. There was no significant difference between the pyuria and non-pyuria groups regarding febrile UTI, emergency visits, and stone-free rate. Multivariate analysis revealed that pyuria was neither significantly associated with postoperative febrile UTI (OR = 1.03, 95% CI = 0.06-18.10, P = 0.98), nor with emergency visits (OR = 0.48, 95% CI = 0.13-1.85, P = 0.29). CONCLUSIONS: Compared to the patients with sterile urine prior to URSL, those with asymptomatic pyuria were not prone to develop febrile UTI after URSL.

Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins.

Alterations in lipoprotein metabolism enhance the risk of cardiometabolic disorders including type-2 diabetes and atherosclerosis, the leading cause of death in Western societies. While the transcriptional regulation of lipid metabolism has been well characterized, recent studies have uncovered the importance of microRNAs (miRNAs), long-non-coding RNAs (lncRNAs) and RNA binding proteins (RBP) in regulating the expression of lipid-related genes at the posttranscriptional level. Work from several groups has identified a number of miRNAs, including miR-33, miR-122 and miR-148a, that play a prominent role in controlling cholesterol homeostasis and lipoprotein metabolism. Importantly, dysregulation of miRNA expression has been associated with dyslipidemia, suggesting that manipulating the expression of these miRNAs could be a useful therapeutic approach to ameliorate cardiovascular disease (CVD). The role of lncRNAs in regulating lipid metabolism has recently emerged and several groups have demonstrated their regulation of lipoprotein metabolism. However, given the high abundance of lncRNAs and the poor-genetic conservation between species, much work will be needed to elucidate the specific role of lncRNAs in controlling lipoprotein metabolism. In this review article, we summarize recent findings in the field and highlight the specific contribution of lncRNAs and RBPs in regulating lipid metabolism.

Stroke Outcome Prediction by Blood Pressure Variability, Heart Rate Variability, and Baroreflex Sensitivity.

Background and Purpose- Poststroke autonomic dysfunction portended an unfavorable prognosis. We investigated whether blood pressure variability (BPV), heart rate variability, and baroreflex sensitivity might predict stroke functional outcome. Methods- We calculated BPV, heart rate variability, baroreflex slope, and baroreflex effectiveness index from a 5-minute beat-to-beat blood pressure and heart rate monitoring within 7 days from the stroke onset. We compared the parameters between patients with a good outcome (modified Rankin Scale score, 0-2) and those with a poor outcome. Results- Among 142 patients (mean age, 63.9±10.2 years; 88.0% men), functional outcome was good in 112 (78.9%) and poor in 30 (21.1%). There were significant differences in admission National Institutes of Health Stroke Scale, prior stroke, high-frequency systolic BPV, low/high-frequency ratio of BPV, baroreflex sensitivity-up, and baroreflex sensitivity-total between the 2 groups (all P<0.05). In multivariate analysis, National Institutes of Health Stroke Scale (OR, 1.672 [95% CI, 1.316-2.125]; P<0.001), low/high-frequency ratio of systolic BPV (OR, 0.493 [95% CI, 0.250-0.973]; P=0.041), and baroreflex effectiveness index-down (OR, 0.958 [95% CI, 0.924-0.992]; P=0.017) independently predicted a poor functional outcome. Conclusions- A decreased low/high-frequency ratio of systolic BPV and impaired baroreflex sensitivity predicted an unfavorable stroke outcome, in addition to the established prognostic factor such as the National Institutes of Health Stroke Scale.