Comorbidity of white matter lesions in parkinson's disease: a study on risk factors and phenotypic differences.

BACKGROUND: Comorbidity of white matter lesions (WMLs) in idiopathic Parkinson's disease (PD) is becoming increasingly common. OBJECTIVE: To analyze the risk factors and phenotypic differences for the occurrence and severity of WMLs in patients with PD. METHODS: A total of 123 PD patients underwent clinical, laboratory, and magnetic resonance imaging (MRI) evaluations. RESULTS: PD patients with WMLs were found to have a higher association with age, Modified Hoehn & Yahr stage (H-Y stage), and hypertension. There was a certain correlation between the severity of WMLs and PD phenotypes. 89% of PD patients had periventricular hyperintensities (PVH). Additionally, the score of the modified version of the Scheltens visual rating scale of PVH in the postural instability gait difficulty (PIGD) phenotype of PD was significantly higher than that in the tremor-dominant (TD) phenotype. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in the PIGD group were significantly lower than those in the TD group. Furthermore, compared with the TD group, the serum homocysteine level was significantly higher in the PIGD group. CONCLUSIONS: Age, H-Y stage, and hypertension are independent risk factors for WMLs in PD, and the severity of WMLs is related to the phenotype of PD patients. Our study found that PVH is the most common occurrence of WMLs in Parkinson's disease, and the burden of PVH is significantly higher in the PIGD phenotype compared to the TD phenotype of PD. Additionally, the PIGD phenotype is associated with more severe cognitive decline and elevated homocysteine levels.

Switching CO2 Electroreduction Pathways between Ethylene and Ethanol via Tuning Microenvironment of the Coating on Copper Nanofibers.

Engineering the microenvironment of electrode surface is one of the effective means to tune the reaction pathways in CO2RR. In this work, we prepared copper nanofibers with conductive polypyrrole coating by polymerization of pyrrole using polyvinyl pyrrolidone (PVP) as template. As a result, the obtained copper nanofibers Cu/Cu2+1O/SHNC, exhibited a superhydrophobic surface, which demonstrated very high selectivity for ethanol with a Faraday efficiency (FE) of 66.5 % at -1.1 V vs reversible hydrogen electrode (RHE) in flow cell. However, the catalyst Cu/Cu2+1O/NC, which was prepared under the same conditions but without PVP, possessed a hydrophobic surface and exhibited high selectivity towards ethylene at the given potentials. The mechanism for switch of reaction pathways from ethylene to ethanol in CO2RR was studied. Incorporating pyrrolidone groups into the polymer coating results in the formation of a superhydrophobic surface. This surface weakens the hydrogen bonding interaction between interfacial water molecules and facilitates the transfer of CO2, thereby enhancing the local CO2/H2O ratio. The high coverage of *CO promotes the coupling of *CO and *CHO to form C2 intermediates, and reduces the reaction energy for the formation of *CHCHOH (ethanol path) at the interface. This ensures that the reaction pathway is directed towards ethanol.

Single Unit-Cell Layered Bi2 Fe4 O9 Nanosheets: Synthesis, Formation Mechanism, and Anisotropic Thermal Expansion.

As an important multiferroic material, pure and low-dimensional phase-stable bismuth ferrite has wide applications. Herein, one-pot hydrothermal method was used to synthesize bismuth ferrite. Almost pure Bi2 Fe4 O9 , BiFeO3 , and their mixture were successfully obtained by controlling the KOH concentration in the hydrothermal solutions. The as-prepared Bi2 Fe4 O9 products were crystalline with Pbam space group, had nanosheet morphology, and tended to aggregate into nanofloret or random stacking. Each Bi2 Fe4 O9 nanosheet was a single crystal with (001) plane as its exposed surface. Single unit-cell layered Bi2 Fe4 O9 nanosheets had a uniform thickness of 1 nm. The surface energies of various (100), (010), and (001) planes were 3.6-4.0, 5.6-15.1, and 1.7-3.0 J m-2 , respectively, in the Bi2 Fe4 O9 crystal. The formation mechanism and structural model of the as-prepared single unit-cell layered Bi2 Fe4 O9 nanosheets have been given. The growth of Bi2 Fe4 O9 nanosheets was discussed. Thermal analysis showed that the Bi2 Fe4 O9 phase was stable up to 1260 K. The thermal expansion behavior of the Bi2 Fe4 O9 nanosheet was nonlinear. The thermal expansion coefficients of the ultrathin Bi2 Fe4 O9 nanosheets on the a-, b-, c-axes, and on the unit-cell volume V were determined, showing an anisotropic thermal expansion behavior. This study is helpful for the controllable synthesis of ultrathin Bi2 Fe4 O9 nanosheets.

Crystalline Structure and Thermal Stability of an Unknown ZIF-L300 Phase.

In recent years, the synthesis, crystalline structure, and applications of zeolite imidazole frameworks (ZIFs) have attracted extensive attention. Since the ZIF-L phase was synthesized, a new phase was observed during the heating process, but its crystal structure is unknown. The unknown new phase, which was named ZIF-L300 in this study, was confirmed again. In this study, the X-ray powder diffraction technique and Rietveld refinement were used to solve the crystalline structure of the unknown ZIF-L300 phase. The results demonstrate that ZIF-L300 has the same chemical formula (ZnC8N4H10) as in ZIF-8 and belongs to a hexagonal structure with a space group of P61. The lattice parameters have been determined as follows: a = b = 8.708(7) Å, c = 24.195(19) Å, α = ß = 90°, and γ = 120°. The X-ray absorption fine structure (XAFS) technique was also used to extract the local atomic structures. The in situ X-ray diffraction (XRD) technique was used to monitor the structural evolution of the as-prepared ZIF-L in a temperature range from room temperature to 600 °C. The results show that the sample experiences a change process from the initial ZIF-L orthorhombic phase (<210 °C), to the ZIF-L300 hexagonal phase (∼300 °C), then to an amorphous phase (∼390 °C), and finally to a zincite ZnO phase (>420 °C). These sorts of structural information are helpful to the application of ZIF materials and enrich the knowledge of the thermal stability of ZIF materials.

Sleep disorders in Wilson's disease: a questionnaire study.

OBJECTIVE: To examine the clinical characteristics and influencing factors related to sleep disorders in patients with Wilson's disease (WD), and investigate its potential mechanisms. METHODS: A total of 150 patients with WD (76 hepatic, 42 neurological, 32 asymptomatic form) and 150 age- and sex-matched control subjects were investigated using 3 standardized sleep questionnaires. Differences among 3 subtypes were discussed. RESULTS: The mean Parkinson's disease sleep scale (PDSS) score of WD was lower than the controls (Z = - 4.426, P = 0.000), and their mean Epworth Sleepiness Scale (ESS) score as well as Pittsburgh sleep quality index (PSQI) score of WD was higher than that of the controls (t = 2.005, P = 0.048; t = 3.342, P = 0.001). The incidence of excessive daytime sleepiness (EDS) in WD group were significantly higher than the controls (X2 = 6.064, P = 0.014). Further analysis showed that total PDSS score of neurologic presentation group was lower than others (X2 = 6.131, P = 0.047), while the ESS score was higher (F = 3.817, P = 0.029). UWDRS showed a negative correlation with PDSS (r = - 0.440, P = 0.022) and has a higher negative correlation with PDSS in neurologic presentation group (r = - 0.732, P = 0.000). CONCLUSIONS: Patients with WD often suffer from sleep disturbances, mainly characterized by difficulty falling asleep, difficulty staying asleep, nocturnal motor symptoms (numbness, cramps, tremor), and daytime dozing. And the incidence of EDS is significantly higher than that of the controls. Sleep quality is worse in patients with WD of neurologic presentation than the other two groups. Furthermore, the worse of the symptoms, patients with WD suffer more serious of the sleep disorders especially in neurologic presentation group.

Long-Range Cationic Disordering Induces two Distinct Degradation Pathways in Co-Free Ni-Rich Layered Cathodes.

Ni-rich layered oxides are one of the most attractive cathode materials in high-energy-density lithium-ion batteries, their degradation mechanisms are still not completely elucidated. Herein, we report a strong dependence of degradation pathways on the long-range cationic disordering of Co-free Ni-rich Li1-m (Ni0.94 Al0.06 )1+m O2 (NA). Interestingly, a disordered layered phase with lattice mismatch can be easily formed in the near-surface region of NA particles with very low cation disorder (NA-LCD, m≤0.06) over electrochemical cycling, while the layered structure is basically maintained in the core of particles forming a "core-shell" structure. Such surface reconstruction triggers a rapid capacity decay during the first 100 cycles between 2.7 and 4.3 V at 1 C or 3 C. On the contrary, the local lattice distortions are gradually accumulated throughout the whole NA particles with higher degrees of cation disorder (NA-HCD, 0.06≤m≤0.15) that lead to a slow capacity decay upon cycling.

A polycrystalline diamond micro-detector for X-ray absorption fine-structure measurements.

The microminiaturization of detectors used to record the intensity of X-ray beams is very favorable for combined X-ray experimental techniques. In this paper, chemical-vapor-deposited (CVD) polycrystalline diamond film was used to fabricate a micro-detector owing to its well controlled size, good thermostability, and appropriate conductivity. The preparation process and the main components of the CVD diamond micro-detector are described. The external dimensions of the packaged CVD diamond micro-detector are 15 mm × 7.8 mm × 5.8 mm. To demonstrate the performance of the detector, K-edge X-ray absorption fine-structure (XAFS) spectra of Cr, Fe, Cu, and Se foils were collected using the CVD diamond micro-detector and routine ion chamber. These XAFS measurements were performed at beamline 1W2B of Beijing Synchrotron Radiation Facility, covering an energy range from 5.5 to 13.5 keV. By comparison, it can be seen that the CVD diamond micro-detector shows a more excellent performance than the routine ion-chamber in recording these XAFS spectra. The successful application of the CVD diamond micro-detector in XAFS measurements shows its feasibility in recording X-ray intensity.

Comparison of vacuum suction ureteroscopic laser lithotripsy and traditional ureteroscopic laser lithotripsy for impacted upper ureteral stones.

PURPOSE: To compare a novel vacuum suction ureteroscopic laser lithotripsy (VS-URS) with traditional ureteroscopic laser lithotripsy (T-URS) for impacted upper ureteral stones and to better define the potential benefits of VS-URS. METHODS: Between May 2019 and March 2021, 158 patients with impacted upper ureteral stones underwent ureteroscopic holmium-YAG laser lithotripsy. Of these, 76 underwent VS-URS and 82 underwent T-URS. In VS-URS procedures, the vacuum suction device is composed of a 5F ureteral catheter and a tee joint. The ureteral catheter is linked to the vacuum aspirator by the sidearm of the tee joint, and a 200 µm fiber is inserted through the tee joint and the ureteral catheter into the stone site for lithotripsy. RESULTS: When compared to the T-URS group, the VS-URS group had a shorter mean operation time (38.18 ± 6.37 min vs. 46.65 ± 5.66 min; P = 0.000), lower fever rate (3.9% vs. 14.6%; P < 0.022), less stone retropulsion (5.3% vs. 18.3%; P = 0.012), lower extra management rate (6.58% vs. 21.95%; P = 0.006), and a higher stone-free rate of the first postoperative day (88.2% vs. 72.0%; P = 0.011). There were no significant differences in stone-free rates 1 month after surgery between groups (94.7% vs. 92.7%; P = 0.748). CONCLUSIONS: VS-URS is an effective modality for impacted upper ureteral stones, and has a shorter operating time, lower fever rate, less stone retropulsion, and a higher primary stone-free rate compared with T-URS.

Hydrothermal Synthesis and Formation Mechanism of Self-Assembled Strings of CoOOH Nanodiscs.

The formation and self-assembly mechanisms of nanomaterials are of great significance for the preparation and application of materials. In this study, the orientationally aggregated CoOOH nanosheets and the self-assembled strings of CoOOH nanodiscs were prepared by hydrothermal method. The formation and self-assembly mechanisms of CoOOH nanodiscs were investigated by XRD, XPS, DLS, TEM, and SEM techniques, as well as DFT calculations. The results show that the formation process of the stacked CoOOH nanodiscs was driven by surface energy and can be divided into four steps: nucleation and growth of CoOOH primary nanosheets; oriented attachment of CoOOH nanosheets; self-assembly of CoOOH nanodiscs; and aggregation of strings of CoOOH nanodiscs. This study contributes meaningfully to the controllable preparation of CoOOH nanomaterials.

Hydrothermal Synthesis and Structures of Unknown Intermediate Phase Zn(HCO3)2·H2O Nanoflakes and Final ZnO Nanorods.

The formation mechanism of nanoparticles is of great significance for the controllable synthesis, structural design, and performance optimization of nanomaterials. In this paper, an economical hydrothermal method was used to synthesize zinc oxide (ZnO) nanorods. X-ray diffraction, X-ray absorption fine structure, and small-angle X-ray scattering techniques were used to probe the structural changes. Scanning electron microscopy and high-resolution transmission electron microscopy were used to observe the morphologies of the products. A self-designed in situ temperature-pressure sample cell was used to control the hydrothermal conditions. The results demonstrate that an unknown intermediate phase, Zn(HCO3)2·H2O, was first formed at 50 °C, having a morphology of nanoflakes with a average thickness of about 35 nm. The intermediate phase Zn(HCO3)2·H2O was determined to have a monoclinic structure with space group P1211 and the following lattice parameters: a = 11.567 Å, b = 3.410 Å, c = 5.358 Å, ß = 96.0011°, and Z = 2. After a hydrothermal temperature of 140 °C, CO2 and H2O were evaporated from the Zn(HCO3)2·H2O intermediate product and the ZnO nanorods with a wurtzite structure were formed. The final ZnO nanorods have an average diameter of about 45 nm and an average length of about 2 µm. The axial direction of the ZnO nanorods is the [001] crystallographic direction. By virtue of understanding the formation mechanism, this work is helpful for the controllable synthesis of ZnO nanoparticles.

Double-Sheath Vacuum Suction Minimally Invasive Percutaneous Nephrolithotomy for Management of Large Renal Stones.

OBJECTIVES: This study aimed to describe a novel double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (mini-PCNL) to overcome the deficiencies of the conventional procedure. PATIENTS AND METHODS: Between March 2019 and December 2019, 65 patients (37 males and 28 females) with a mean age of 41 years (range 23-69) underwent mini-PCNL with double-sheath vacuum suction. It consisted of an F20 Y-shaped sheath as an outer sheath and an F16 Y-shaped sheath as an inner sheath, in which the inner sheath was longer than the outer sheath. The oblique arm of the outer sheath and the inner sheath was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was introduced for stone fragmentation through the working channel of the mini-nephroscope, which was no longer connected to the perfusion fluid. RESULTS: All procedures were successful. Mean operation time was 50.2 min (range 39-83). Mean hemoglobin decrease was 5.2 g/L (range 1.0-15.5), and no patient needed a blood transfusion. One patient (1.5%) with low fever (<38°C) at day 1 had returned to normal at day 2 without administration of antibiotics. There were no Clavien grade 2-4 complications. Mean postoperative hospital stay was 2.4 days (range 2-6). The initial stone-free rate of PCNL was 81.53% (53 of 65 patients). One month after surgery, the final stone-free rate increased to 90.77% (59/65 patients). CONCLUSIONS: The double-sheath vacuum suction mini-PCNL is a safe and effective modality for large renal stones, which might increase the efficiency of stone extraction with low intrapelvic pressure.

Growth and physiological responses in a submerged clonal aquatic plant and multiple-endpoint assessment under prolonged exposure to ciprofloxacin.

Ciprofloxacin is ubiquitous and poses a potential threat to aquatic ecosystems. However, the comprehensive effect of prolonged ciprofloxacin exposure on the submerged clonal plant Vallisneria natans (Lour.) Hara remains unknown. Growth and physiological responses in V. natans exposed to ciprofloxacin at concentrations of 0, 0.05, 0.25, 1.25, 2.5, 5 and 10 mg/L were repeatedly evaluated on Days 7, 14, 28, 42 and 56. V. natans maintained good growth properties under 0.05-0.25 mg/L ciprofloxacin treatments, while the inhibition effect on plant growth induced by higher-concentration treatments increased over time. The IC50 values of ciprofloxacin for growth endpoints ranged from 1.6 mg/L to 5.3 mg/L and displayed time-dependent decreases. Pigment contents were significantly stimulated by ciprofloxacin on Day 7 but decreased to varying degrees as the exposure time was extended. Soluble protein and hydrogen peroxide content rose significantly over the first 14 days of treatment with 0.25-10 mg/L ciprofloxacin but decreased under 1.25-10 mg/L ciprofloxacin treatments since Day 28. Antioxidants including superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase and proline functioned well in mitigating oxidative stress under different ciprofloxacin concentrations, lowering the comprehensive toxic effects of ciprofloxacin on V. natans during the period from Day 14 to Day 42, as evidenced by decreased IBR (integrated biomarker response) values. However, the toxic pressure of ciprofloxacin on V. natans peaked on Day 56. These findings suggest that exposure time can influence the responses of V. natans exposed to ciprofloxacin and that IBR can be employed to evaluate the integrated impacts of prolonged ciprofloxacin contamination in aquatic settings.

Trace elements in public drinking water in Chinese cities: Insights from their health risks and mineral nutrition assessments.

The trace elements in the public drinking water have a duality: on the one hand, trace elements play an important role in maintaining human metabolism; on the other hand, high trace elements levels lead to significant health risks. To determine the impacts of trace elements in the public drinking water on physical health in China, water samples were collected from 314 Chinese cities to analyze the concentrations and spatial distributions of trace elements on a national scale. On this basis, the non-carcinogenic health risk assessments and the nutrient-based scores of trace elements (NSTEs) were applied to evaluate the public drinking water quality in terms of safety and nutrition. Most of the water samples were weakly alkaline: pH values fell in the range of 6.62-8.54, with a mean of 7.80. The results indicated that Sr and F- had the highest concentrations in public drinking water, with averages of 0.3604 mg/L and 0.2351 mg/L, respectively. Moreover, hazard index (HI) values in different regions followed the order: northwest China (NWC) > northern China (NC) > Qinghai-Tibetan Plateau (QT) > southern China (SC). The percentages of water samples with HI > 1 in SC, NC, NWC, and QT were 5.49%, 16.82%, 25.81%, and 16.67%, respectively, indicating that the public drinking water in some cities had significant non-carcinogenic health risks. In addition, the intakes of Mn, Fe, Cu, and Rb through public drinking water made negligible contributions to their recommended nutrient intakes. In contrast, trace elements like Sr, F, B, Li, Mo, etc., contributed a lot. The NSTEs in NWC and most parts of NC were relatively high with averages of 8.0300 and 11.2082, respectively; however, the NSTEs in SC and the northeast part of NC were low with averages of 3.3284 and 5.2106, respectively. The results from this study provide a reference for establishing the public drinking water standards and improving drinking water quality.

The Determination Method of Satisfactory Consistency of the Interval Number Pairwise Comparisons Matrix Based on Submatrix.

The decision-maker obtains the pairwise comparisons matrix by comparing two entities. In the process of comparing the two entities, the relationship between the two entities and other entities is not considered. In this way, the judgment may be illogical. This paper mainly studies the satisfactory consistency of the interval number pairwise comparisons matrix based on cyclic matrix. Firstly, the illogical judgment entity in the process of the decision-maker's judgment is expressed by the cyclic matrix. There are three entities and four entities to form the cyclic matrix. The relationship and various forms of the cyclic cycle formed by the four entities and the three entities are discussed; then, the satisfactory consistency of the interval number pairwise comparisons matrix is determined by judging whether there is a cyclic matrix in the submatrix of the interval number pairwise comparisons matrix. Finally, two examples are given to verify the rationality and effectiveness of the method.

M2a macrophage can rescue proliferation and gene expression of benign prostate hyperplasia epithelial and stroma cells from insulin-like growth factor 1 knockdown.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in elderly men and is often accompanied by chronic inflammation. Macrophages (several subtypes) are the main inflammatory cells that infiltrate the hyperplastic prostate and are found to secrete cytokines and growth factors. The current study aims to explore the effect of M2a macrophages on the development of BPH via insulin-like growth factor 1 (IGF-1). METHODS: Human prostate tissues, prostate, and monocyte cell lines (WPMY-1, BPH-1, and THP-1) were used. THP-1 was polarized into several subtypes with cytokines. The expression and localization of IGF-1 and M2 macrophages were determined via immunofluorescent staining, quantitative real-time polymerase chain reaction, and Western blot analysis. Flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to investigate the effects of different subtypes of macrophages on prostate cells. IGF-1 in WPMY-1 and BPH-1 cells was silenced and cocultured with or without M2a macrophages. Cell proliferation, apoptosis, cell cycle, epithelial-mesenchymal transition (EMT), and fibrosis processes were examined. RESULTS: The polarized subtypes of macrophages were verified by amplifying their specific markers. M2a macrophages enhanced prostate cell proliferation more significantly and CD206 was more expressed in hyperplastic prostate. IGF-1 was localized in both epithelial and stromal components of prostate and upregulated in BPH tissues. M2a macrophages expressed more IGF-1 than other subtypes. Knockdown of IGF-1 in WPMY-1 and BPH-1 cells attenuated cell proliferation, promoted cell apoptosis, retarded cell cycle at the G0/G1 phase, and suppressed the EMT process in BPH-1 cells as well as the fibrotic process in WPMY-1 cells, which was reversible when cocultured with M2a macrophages. CONCLUSION: These data demonstrated that knockdown of IGF-1 expression in cultured BPH epithelial and stromal cells reduces proliferation and increases apoptosis. These effects are reversed by coculture with M2a macrophages.

Double-sheath vacuum suction versus vacuum-assisted sheath minimally invasive percutaneous nephrolithotomy for management of large renal stones: single-center experience.

PURPOSE: To compare double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (DS-mini-PCNL) with vacuum-assisted mini-PCNL (VS-mini-PCNL) and to better define the potential benefits of DS-mini-PCNL. METHODS: Between July 2019 and May 2020, 117 patients with large radiopaque renal stones underwent mini-PCNL. Of these, 63 underwent DS-mini-PCNL and 54 underwent VS-mini-PCNL. For VS-mini-PCNL, a F20 Y-shaped sheath was used and the oblique arm of the sheath was connected to the vacuum suction. For DS-mini-PCNL, the oblique arm of a F20 Y-shaped sheath (the outer sheath) and a F16 Y-shaped sheath (the inner sheath) was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was used for stone fragmentation. RESULTS: Compared with VS-mini-PCNL group, DS-mini-PCNL group had significantly shorter operative time (35.78 ± 7.77 min vs. 44.56 ± 13.19 min; P = 0.000) and significantly lower fever rate (1.6% vs. 11.1%; P = 0.048). It was not significantly different between the two groups despite the higher initial stone-free rate seen for DS-mini-PCNL group relative to VS-mini-PCNL group (87.7% vs. 81.5%, P = 0.346). Auxiliary procedure rates were 4.8% (three patients) in DS-mini-PCNL group and 16.7% (nine patients) in VS-mini-PCNL group, with a significant difference (P = 0.034). The difference in the final stone-free rate between the two groups was rendered insignificant (93.8% vs. 89.1%, P = 0.510). CONCLUSIONS: DS-mini-PCNL is a safe and effective modality for large renal stones, which could increase the efficiency of stone extraction and decrease infectious complications compared with VS-mini-PCNL.

Changes in the expression and function of the PDE5 pathway in the obstructed urinary bladder.

Our study aims to explore changes in bladder contractility and the phosphodiesterase type 5 (PDE5) signalling pathway in response to partial bladder outlet obstruction (PBOO). A surgically induced male rat PBOO model and human obstructed bladder tissues were used. Histological changes were examined by H&E and Masson's trichrome staining. Bladder strip contractility was measured via organ bath. The expressions of nitric oxide synthase (NOS) isoforms, PDE5, muscarinic cholinergic receptor (CHRM) isoforms and PDE4 isoforms in bladder were detected by RT-PCR and Western blotting. The immunolocalization of the PDE5 protein and its functional activity were also determined. PBOO bladder tissue exhibited significant SM hypertrophy and elevated responsiveness to KCl depolarization and the muscarinic receptor agonist carbachol. NOS isoforms, PDE5, CHRM2, CHRM3 and PDE4A were up-regulated in obstructed bladder tissue, whereas no change in PDE4B and PDE4D isoform expression was observed. With regard to PDE5, it was expressed in the SM bundles of bladder. Interestingly, obstructed bladder exhibited less relaxation responsiveness to sodium nitroprusside (SNP), but an exaggerated PDE5 inhibition effect. The up-regulation of PDE5 could contribute to the lack of effect on Qmax for benign prostatic hyperplasia/lower urinary tract symptom (BPH/LUTS) patients treated with PDE5 inhibitors. Moreover, PDE5 (with presence of NO) and PDE4 may serve as new therapeutic targets for bladder diseases such as BPH-induced LUTS and overactive bladder (OAB).

Actinide Separation Inspired by Self-Assembled Metal-Polyphenolic Nanocages.

The separation of actinides has a vital place in nuclear fuel reprocessing, recovery of radionuclides, and remediation of environmental contamination. Here we propose a new paradigm of nanocluster-based actinide separation, namely, nanoextraction, that can achieve efficient sequestration of uranium in an unprecedented form of giant coordination nanocages using a cone-shaped macrocyclic pyrogallol[4]arene as the extractant. The U24-based hexameric pyrogallol[4]arene nanocages with distinctive [U2(PG)2] binuclear units (PG = pyrogallol) that rapidly assembled in situ in monophasic solvent were identified by single-crystal X-ray diffraction, MALDI-TOF mass spectrometry, NMR spectroscopy, and small-angle X-ray and neutron scattering. Comprehensive biphasic extraction studies showed that this novel separation strategy has enticing advantages such as fast kinetics, high efficiency, and good selectivity over lanthanides, thereby demonstrating its potential for efficient separation of actinide ions.

Quality assessment for the putative intrinsic disorder in proteins.

MOTIVATION: While putative intrinsic disorder is widely used, none of the predictors provides quality assessment (QA) scores. QA scores estimate the likelihood that predictions are correct at a residue level and have been applied in other bioinformatics areas. We recently reported that QA scores derived from putative disorder propensities perform relatively poorly for native disordered residues. Here we design and validate a general approach to construct QA predictors for disorder predictions. RESULTS: The QUARTER (QUality Assessment for pRotein inTrinsic disordEr pRedictions) toolbox of methods accommodates a diverse set of ten disorder predictors. It builds upon several innovative design elements including use and scaling of selected physicochemical properties of the input sequence, post-processing of disorder propensity scores, and a feature selection that optimizes the predictive models to a specific disorder predictor. We empirically establish that each one of these elements contributes to the overall predictive performance of our tool and that QUARTER's outputs significantly outperform QA scores derived from the outputs generated the disorder predictors. The best performing QA scores for a single disorder predictor identify 13% of residues that are predicted with 98% precision. QA scores computed by combining results of the ten disorder predictors cover 40% of residues with 95% precision. Case studies are used to show how to interpret the QA scores. QA scores based on the high precision combined predictions are applied to analyze disorder in the human proteome. AVAILABILITY AND IMPLEMENTATION: http://biomine.cs.vcu.edu/servers/QUARTER/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association between body mass index and survival outcomes for cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been increasingly applied in the treatment of several kinds of malignancies. Some clinical demographic characteristics were reported to be associated with the ICIs efficacy. The purpose of our current meta-analysis was to clearly evaluated the relationship between BMI and ICIs efficacy for cancer patients receiving immunotherapy. METHODS: A systematic search of Pubmed, EMBASE and conference proceedings was performed to investigate the influence of BMI on ICIs efficacy. Pooled analysis for overall survival (OS), progression-free survival (PFS) and immune-related adverse effects (IRAEs) were analyzed in current study. RESULTS: A total of 13 eligible studies comprising 5279 cancer patients treated with ICIs were included in the analysis. The pooled analysis showed there is positive association between high BMI and improved OS and PFS among patients with ICIs treatment (OS: HR = 0.62, 95% CI 0.55-0.71, P < 0.0001; I2 = 26.3%, P = 0.202); PFS: HR = 0.71, 95% CI 0.61-0.83, P < 0.0001; I2 = 0%, P = 0.591). There is no significant difference between the incidence of all grade IRAEs between obese, overweight patients and normal patients (Overweight vs Normal: pooled RR = 1.28, 95% CI 0.76- 2.18, P = 0.356; Obese vs Normal: pooled RR = 1.36, 95% CI 0.85- 2.17, P = 0.207). CONCLUSION: An improved OS and PFS were observed in patients with high BMI after receiving ICIs treatment compared with patients of low BMI. No significant association between BMI and incidence of IRAEs was found in cancer patients after ICIs treatment.