Atorvastatin-induced intracerebral hemorrhage is inhibited by berberine in zebrafish.

Intracerebral hemorrhage (ICH), for which there are currently no effective preventive or treatment methods, has a very high fatality rate. Statins, such as atorvastatin (ATV), are the first-line drugs for regulating blood lipids and treating hyperlipidemia-related cardiovascular diseases. However, ATV-associated ICH has been reported, although its incidence is rare. In this study, we aimed to investigate the protective action and mechanisms of berberine (BBR) against ATV-induced brain hemorrhage. We established an ICH model in zebrafish induced by ATV (2 µM) and demonstrated the effects of BBR (10, 50, and 100 µM) on ICH via protecting the vascular network using hemocyte staining and three transgenic zebrafish. BBR was found to reduce brain inflammation and locomotion injury in ICH-zebrafish. Mechanism research showed that ATV increased the levels of VE-cadherin and occludin proteins but disturbed their localization at the cell membrane by abnormal phosphorylation, which decreased the number of intercellular junctions between vascular endothelial cells (VECs), disrupting the integrity of vascular walls. BBR reversed the effects of ATV by promoting autophagic degradation of phosphorylated VE-cadherin and occludin in ATV-induced VECs examined by co-immunoprecipitation (co-IP). These findings provide crucial insights into understanding the BBR mechanisms involved in the maintenance of vascular integrity and in mitigating adverse reactions to ATV.

Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside.

The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), are complex and multifaceted. A growing body of evidence suggests that the gut microbiome plays crucial roles in the development and progression of neurodegenerative diseases. Clinicians have come to realize that therapeutics targeting the gut microbiome have the potential to halt the progression of neurodegenerative diseases. This narrative review examines the alterations in the gut microbiome in AD, PD, ALS and HD, highlighting the close relationship between the gut microbiome and the brain in neurodegenerative diseases. Processes that mediate the gut microbiome-brain communication in neurodegenerative diseases, including the immunological, vagus nerve and circulatory pathways, are evaluated. Furthermore, we summarize potential therapeutics for neurodegenerative diseases that modify the gut microbiome and its metabolites, including diets, probiotics and prebiotics, microbial metabolites, antibacterials and faecal microbiome transplantation. Finally, current challenges and future directions are discussed.

Effect of the type of brewing water on the sensory and physicochemical properties of light-scented and strong-scented Tieguanyin oolong teas.

Variations in the quality of brewing water profoundly impact tea flavor. This study systematically investigated the effects of four common water sources, including pure water (PW), mountain spring water (MSW), mineral water (MW) and natural water (NW) on the flavor of Tieguanyin tea infusion. Brewing with MW resulted in a flat taste and turbid aroma, mainly due to the low leaching of tea flavor components and complex interactions with mineral ions (mainly Ca2+, Mg2+). Tea infusions brewed with NW exhibited the highest relative contents of total volatile compounds, while those brewed with PW had the lowest. NW and MSW, with moderate mineralization, were conducive to improving the aroma quality of tea infusion and were more suitable for brewing both aroma types of Tieguanyin. These findings offer valuable insights into the effect of brewing water on the sensory and physicochemical properties of oolong teas.

Bridging Component Strategy in Phosphomolybdate-Based Sensors for Electrochemical Determination of Trace Cr(VI).

Rapid and sensitive electrochemical determination of trace carcinogenic Cr(VI) pollutants remains an urgent and important task, which requires the development of active sensing materials. Herein, four cases of reduced phosphomolybdates with formulas of the (H2bib)3[Zn(H2PO4)]2{Mn[P4Mo6O31H7]2}·6H2O (1), (H2bib)2[Na(H2O)]2[Mn(H2O)]2{Mn[P4Mo6O31H6]2}·5H2O (2), (H2bib)3[Mo2(µ2-O)2(H2O)4]2{Ni[P4Mo6O31H2]2}·4H2O (3), and (H2bib)2{Ni[P4Mo6O31H9]2}·9H2O (4) (bib = 4,4'-bis(1-imidazolyl)-biphenyl) were hydrothermally synthesized under the guidance of a bridging component strategy, which function as effective electrochemical sensors to detect trace Cr(VI). The difference of hybrids 1-4 is in the inorganic moiety, in which the reduced phosphomolybdates {M[P4MoV6O31]2} (M{P4Mo6}2) exhibited different arrangements bridged by different cationic components ({Zn(H2PO4)} subunit for 1, [Mn2(H2O)2]4+ dimer for 2, and [MoV2(µ2-O)2(H2O)4]6+ for 3). As a result, hybrids 1 and 3 display noticeable Cr(VI) detection activity with low detection limits of 14.3 nM (1.48 ppb) for 1 and 6.61 nM (0.69 ppb) for 3 and high sensitivities of 97.3 and 95.3 µA·mM-1, respectively, which are much beyond the World Health Organization's detection threshold (0.05 ppm) and superior to those of the contrast samples (inorganic Mn{P4Mo6}2 salt and hybrid 4), even the most reported noble-metal catalysts. This work supplies a prospective pathway to build effective electrochemical sensors based on phosphomolybdates for environmental pollutant treatment.

Perfect cubic metallo-borospherenes TM8B6 (TM = Ni, Pd, Pt) as superatoms following the 18-electron rule.

Transition-metal (TM)-doped metallo-borospherenes exhibit unique structures and bonding in chemistry which have received considerable attention in recent years. Based on extensive global minimum searches and first-principles theory calculations, we predict herein the first and smallest perfect cubic metallo-borospherenes Oh TM8B6 (TM = Ni (1), Pd (2), Pt (3)) and Oh Ni8B6- (1-) which contain eight equivalent TM atoms at the vertexes of a cube and six quasi-planar tetra-coordinate face-capping boron atoms on the surface. Detailed canonical molecular orbital and adaptive natural density partitioning bonding analyses indicate that Oh TM8B6 (1/2/3) as superatoms possess nine completely delocalized 14c-2e bonds following the 18-electron principle (1S21P61D10), rendering spherical aromaticity and extra stability to the complex systems. Furthermore, Ni8B6 (1) can be used as building blocks to form the three-dimensional metallic binary crystal NiB (4) (Pm3̄m) in a bottom-up approach which possesses a typical CsCl-type structure with an octa-coordinate B atom located exactly at the center of the cubic unit cell. The IR, Raman, UV-vis and photoelectron spectra of the concerned clusters are computationally simulated to facilitate their experimental characterization.

Time-dependent impact of type 2 diabetes mellitus on incident prodromal Alzheimer disease: A longitudinal study in 1395 participants.

BACKGROUND AND PURPOSE: This study was undertaken to investigate the longitudinal impact of type 2 diabetes mellitus (T2DM) on the prodromal and dementia stages of Alzheimer disease (AD), focusing on diabetes duration and other comorbidities. METHODS: A total of 1395 dementia-free individuals aged 55-90 years with maximum 15-year follow-up data were enrolled from the Alzheimer's Disease Neuroimaging Initiative database. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of the incidence of prodromal or dementia stages of AD. RESULTS: Longer T2DM duration (≥5 years; multiadjusted HR = 2.19, 95% confidence interval [CI] = 1.05-4.58), but not shorter T2DM duration (<5 years), was associated with a significantly increased risk of incident prodromal AD over a mean follow-up of 4.8 years. APOE ε4 allele (HR = 3.32, 95% CI = 1.41-7.79) and comorbid coronary artery disease (CAD; HR = 3.20, 95% CI = 1.29-7.95) further increased the risk of incident prodromal AD in patients with T2DM. No significant association was observed between T2DM and the risk of progression from prodromal AD to AD dementia. CONCLUSIONS: T2DM, which is characterized by a longer duration, increases the incidence risk of prodromal AD but not AD dementia. APOE ε4 allele and comorbid CAD strengthen the relationship between T2DM and prodromal AD. These findings highlight T2DM characteristics and its comorbidities as predictors for accurate prediction of AD and screening of at-risk populations.

Bio-Inspired FeMo2S4 Microspheres as Bifunctional Electrocatalysts for Boosting Hydrogen Oxidation/Evolution Reactions in Alkaline Solution.

Developing robust and effectual nonprecious electrocatalysts for the bifunctional hydrogen oxidation and evolution reactions (HOR and HER) in alkaline electrolyte is of critical significance for the realization of future hydrogen economy but challenging. Herein, this work demonstrates a new routine for the preparation of bio-inspired FeMo2S4 microspheres via the one-step sulfuration of Keplerate-type polyoxometalate {Mo72Fe30}. The bio-inspired FeMo2S4 microspheres feature potential-abundant structural defects and atomically precise iron doping and act as an effective bifunctional electrocatalyst for hydrogen oxidation/reduction reactions. The FeMo2S4 catalyst presents an impressive alkaline HOR activity compared to FeS2 and MoS2 with the high mass activity of 1.85 mA·mg-1 and high specific activity as well as excellent tolerance to carbon monoxide poisoning. Meanwhile, FeMo2S4 electrocatalyst also displayed prominent alkaline HER activity with a low overpotential of 78 mV at a current density of 10 mA·cm-2 and robust long-term durableness. Density functional theory (DFT) calculations indicate that the bio-inspired FeMo2S4 with a unique electron structure possesses the optimal hydrogen adsorption energy and enhanced adsorption of hydroxyl intermediates, which accelerates the potential-determining Volmer step, thus promoting the HOR and HER performance. This work provides a new pathway for designing efficient noble-metal-free electrocatalysts for the hydrogen economy.

Heptacoordinate transition-metal-decorated metallo-borospherenes and multiple-helix metallo-boronanotubes.

The recent discovery of lanthanide-metal-decorated metallo-borospherenes LM3B18- (LM = La, Tb) marks the onset of a new class of boron-metal binary nanomaterials. Using the experimentally observed or theoretically predicted borospherenes as ligands and based on extensive first-principles theory calculations, we predict herein a series of novel chiral metallo-borospherenes C2 Ni6 ∈ B39- (1), C1 Ni6 ∈ B41+ (3), C2 Ni6 ∈ B422+ (4), C2 Ni6 ∈ B42 (5), and C2 Ni8 ∈ B56 (6) as the global minima of the systems decorated with quasi-planar heptacoordinate Ni (phNi) centers in η7-B7 heptagons on the cage surfaces, which are found to be obviously better favoured in coordination energies than hexacoordinate Ni centers in previously reported D2d Ni6 ∈ B40 (2). Detailed bonding analyses indicate that these phNi-decorated metallo-borospherenes follow the σ + π double delocalization bonding pattern, with two effective (d-p)σ coordination bonds formed between each phNi and its η7-B7 ligand, rendering spherical aromaticity and extra stability to the systems. The structural motif in elongated axially chiral Ni6 ∈ B422+ (4), Ni6 ∈ B42 (5), and Ni8 ∈ B56 (6) can be extended to form the metallic phNi-decorated boron double chain (BDC) double-helix Ni4 ∈ B28 (2, 0) (P4̄m2) (8), triple-helix Ni6 ∈ B42 (3, 0) (P3̄m1) (9), and quadruple-helix Ni8 ∈ B56 (4, 0) (P4mm) (10) metallo-boronanotubes, which can be viewed as quasi-multiple-helix DNAs composed of interconnected BDCs decorated with phNi centers in η7-B7 heptagons on the tube surfaces in the atomic ratio of Ni : B = 1 : 7.

Correlation analysis of self-directed learning ability, self-efficacy and academic burnout of junior nursing college students in closed management colleges.

AIMS: To understand the status quo of self-directed learning ability, self-efficacy and academic burnout of junior nursing college students, since the closed management mode was implemented during COVID-19 pandemic disease. DESIGN: Cross-sectional study. METHODS: Participants came from 3,051 junior nursing college students of a college in Zhengzhou City, Henan Province, China. Data were collected by online questionnaire and analysed by SPSS25.0 (a statistical package for social science) and AMOS24.0 software. RESULTS: High self-directed learning ability and self-efficacy were related to low levels of academic burnout (p < .01). In addition, the analysis of mediation effect indicated that the influence of self-directed learning ability on academic burnout was not mediated by self-efficacy.

An in silico and in vitro integrated analysis method to reveal the curative mechanisms and pharmacodynamic substances of Bufei granule on chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high disability and mortality. Clinical studies have shown that the Traditional Chinese Medicine Bufei Granule (BFG) has conspicuous effects on relieving cough and improving lung function in patients with COPD and has a reliable effect on the treatment of COPD, whereas the therapeutic mechanism is vague. In the present study, the latent bronchodilators and mechanism of BFG in the treatment of COPD were discussed through the method of network pharmacology. Then, the molecular docking and molecular dynamics simulation were performed to calculate the binding efficacy of corresponding compounds in BFG to muscarinic receptor. Finally, the effects of BFG on bronchial smooth muscle were validated by in vitro experiments. The network pharmacology results manifested the anti-COPD effect of BFG was mainly realized via restraining airway smooth muscle contraction, activating cAMP pathways and relieving oxidative stress. The results of molecular docking and molecular dynamics simulation showed alpinetin could bind to cholinergic receptor muscarinic 3. The in vitro experiment verified both BFG and alpinetin could inhibit the levels of CHRM3 and acetylcholine and could be potential bronchodilators for treating COPD. This study provides an integrating network pharmacology method for understanding the therapeutic mechanisms of traditional Chinese medicine, as well as a new strategy for developing natural medicines for treating COPD.

Three-Dimensional Silver-Containing Polyoxotungstate Frameworks for Photocatalytic Aerobic Oxidation of Benzyl Alcohol.

Photocatalytic organic transformation derived by functionalized polyoxometalate (POM)-based metal-organic frameworks provides a feasible route for fine chemical synthesis. Herein, three kinds of photoactive three-dimensional silver-containing polyoxotungstate frameworks are synthesized with the formulas [Ag3L2(OH)][Na(H2O)0.5][PW12O40]·H2O (1), [Ag4L3][SiW12O40] (2), and [Ag(H2O)][Ag4L3][BW12O40]·9H2O (3) (L = 1,4-di(4H-1,2,4-triazol-4-yl)benzene). In compounds 1-3, the cationic Ag-triazole clusters with diverse nuclei serve as nodes to assemble with rigid bridging ligands (L) and polyoxoanions to extend into stable three-dimensional frameworks, in which Keggin-type anions act as guests or pendants. When using them as heterogeneous photocatalysts, compounds 1-3 show high catalytic activity and selectivity for the photocatalytic aerobic oxidation of benzyl alcohol to benzoic acid under 10 W 365 nm light irradiation. Among them, compound 1 exhibits the highest performance with ca. 99% benzyl alcohol conversion and 99% selectivity of benzoic acid in 9 h. Compounds 2 and 3 show ca. 79 and 88% conversions of benzyl alcohol, respectively, which are higher than those of the individual Keggin-type precursors. Moreover, mechanism investigation suggests that the synergistic cooperation occurring between cationic Ag-triazole clusters and Keggin-type polyoxoanions modulates the energy band structures of compounds 1-3, resulting in the efficient separation of photogenerated carriers and accelerating the aerobic oxidation of benzyl alcohol. This work provides some important guidance for the design and development of efficient POM-based photocatalysts for practical organic transformation.

Bifunctional Sensors Based on Phosphomolybdates for Detection of Inorganic Hexavalent Chromium and Organic Tetracycline.

Exploring effective sensors for detecting possible hazards in a water system are greatly significant. This work proposed a strategy for stable and effective bifunctional sensors via incorporating hourglass-type phosphomolybdates into metal-organic fragments to construct a high-dimensional framework. Two hourglass-type phosphomolybdate-based electrochemical sensors toward heavy metal ion Cr(VI) and tetracycline (TC) detection were designed with the formula [CoII2(H2O)4NaI2][CoII(Hbpe)][NaI(bpe)1.5]{CoII[PV4MoV6O31H6]2}·9H2O (1) and [CoII(H2O)4NaI3][CoII(Hbpe)][CoII(bpe)]{CoII[PV4MoV6O31H6]2}·9H2O (2) [bpe = 1,2-di(4-pyridyl)ethylene]. Structural analysis showed that hybrids 1 and 2 possess three-dimensional POM-supported network features with favorable stability and exhibit reversible redox properties. Experiments found that this kind of hybrids as efficient sensors have excellent electrochemical performance toward Cr(VI) detection with high sensitivities of 0.111 µA·µM-1 for 1 and 0.141 µA·µM-1 for 2, fast response time of 1 s, and low detection limits of 30 nM for 1 and 27 nM for 2, which far meet the standard of WHO for drinking water. Moreover, hybrids 1-2 also exhibit fast responses to TC detection with sensitivities of 0.0073 and 0.022 µA·mM-1 and detection limits of 0.426 and 0.084 mM. This work offers a novel strategy for the purposeful design of efficient POM-based electrochemical sensors for accurate determination of contaminants in a practical water system.

A bottom-up approach from medium-sized bilayer boron nanoclusters to bilayer borophene nanomaterials.

Inspired by the experimentally observed bilayer B48-/0 and theoretically predicted bilayer B50-B72 and based on extensive density functional theory calculations, we report herein a series of novel medium-sized bilayer boron nanoclusters C1 B84 (I), C2v B86 (II), C1 B88 (III), C1 B90 (IV), C1 B92 (V), C1 B94 (VI), C2v B96 (VII), and C1 B98 (VIII) which are the most stable isomers of the systems reported to date effectively stabilized by optimum numbers of interlayer B-B σ bonds between the inward-buckled atoms on top and bottom layers. Detailed bonding analyses indicate that these bilayer species follow the universal bonding pattern of σ + π double delocalization, rendering three-dimensional aromaticity in the systems. More interestingly, the AA-stacked bilayer structural motif in B96 (VII) with a B72 bilayer hexagonal prism at the center can be extended to form bilayer C2 B128 (IX), D2h B214 (X), C2v B260 (XI), D2h B372 (XII), and D2 B828 (XIII) which contain one or multiple conjoined B72 bilayer hexagonal prisms sharing interwoven zig-zag boron triple chains between them. Such bilayer species or their close-lying AB isomers can be viewed as embryos of the newly reported most stable freestanding BL-α+ bilayer borophenes and quasi-freestanding bilayer borophenes on Ag(111) which are composed of interwoven zig-zag boron triple chains shared by conjoined BL B72 hexagonal prisms, presenting a bottom-up approach from medium-sized bilayer boron nanoclusters to two-dimensional bilayer borophene nanomaterials.

Polyoxometalate-Incorporated Metal-Organic Network as a Heterogeneous Catalyst for Selective Oxidation of Aryl Alkenes.

Selective oxidation of aryl alkenes is important for chemical synthesis reactions, in which the key lies in the rational design of efficient catalysts. Herein, four polyoxometalate (POM)-incorporated metal-organic networks, with the formulas of [Co(ttb)(H2O)3]2[SiMo12O40]·2H2O (1), [Co(ttb)(H2O)2]2[SiW12O40]·8H2O (2), [Zn(Httb)(H2ttb)][BW12O40]·9H2O (3) and {[Zn(H2O)3(ttb)]4[Zn3(H2O)6]}[H3SiW10.5Zn1.5O40]2·24H2O (4) (ttb = 1,3,5-tri(1,2,4-triazol-1-ylmethyl)-2,4,6-trimethylbenzene), were hydrothermally synthesized and structurally characterized. Structural analysis showed that compound 1 consists of a POM-encapsulated three-dimensional (3-D) supramolecular framework; compound 2 is composed of a POM-supported 3-D coordination network; and compounds 3-4 show POM-incorporated 3-D supramolecular networks. Using selective catalytic oxidation of styrene as the model reaction, compounds 1-4 as heterogeneous catalysts display excellent performance with the double advantages of high styrene conversion and benzaldehyde selectivity owing to the synergistic effect among POM anions and transition metal (TM) centers. Among them, compound 1 exhibits the highest performance with ca. 96% styrene conversion and ca. 99% benzaldehyde selectivity in 3 h. In addition, compound 1 also displays excellent substrate compatibility, good reusability, and structural stability. Thus, a plausible reaction pathway for the selective oxidation of styrene is proposed. This study on the structure-function relationship paves a way for the rational design of POM-based heterogeneous catalysts for important catalysis applications.

The role of ipRGCs in ocular growth and myopia development.

The increasing global prevalence of myopia calls for elaboration of the pathogenesis of this disease. Here, we show that selective ablation and activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in developing mice induced myopic and hyperopic refractive shifts by modulating the corneal radius of curvature (CRC) and axial length (AL) in an opposite way. Melanopsin- and rod/cone-driven signals of ipRGCs were found to influence refractive development by affecting the AL and CRC, respectively. The role of ipRGCs in myopia progression is evidenced by attenuated form-deprivation myopia magnitudes in ipRGC-ablated and melanopsin-deficient animals and by enhanced melanopsin expression/photoresponses in form-deprived eyes. Cell subtype-specific ablation showed that M1 subtype cells, and probably M2/M3 subtype cells, are involved in ocular development. Thus, ipRGCs contribute substantially to mouse eye growth and myopia development, which may inspire novel strategies for myopia intervention.

Efficient Electrochemical Detection of Hydrogen Peroxide Based on Silver-Centered Preyssler-Type Polyoxometalate Hybrids.

Four polyoxometalate (POM)-based organic-inorganic hybrid compounds, namely, (H2bimb)6H8[((Mn(H2O)3(µ-bimb))0.5(Mn(H2O)4)(Mn(H2O)5)0.5(AgP5W30O110))2]·29H2O (1), [(Cu(Hbimb)(H2O)2(µ-bimb)Cu(Hbimb)(H2O))(Cu(H2O)2(µ-bimb)Cu(H2O)3)((Cu(H2O)2)0.5(µ-bimb)(Cu(H2O)3)0.5)H2(AgP5W30O110)]·12.5H2O (2), (H2bimb)2H[(Zn(Hbimb)(H2O)4(Zn(Hbimb)(H2O)2)0.5)2(AgP5W30O110)]·12H2O (3), and (H2bimb)3H2[(Ag(H2O)2)0.5(Ag(Hbimb)Ag(Hbimb)(µ-bimb)Ag)(Ag(H2O)2)0.5(AgP5W30O110)]·7H2O (4) (bimb = 1,4-bis(1H-imidazol-1-yl)benzene), were hydrothermally synthesized using a silver-centered Preyssler-type POM K14[AgP5W30O110]·18H2O (abbreviated as K-{AgP5W30}) as a precursor. In 1-4, {AgP5W30} clusters integrating the merits of Ag+ and {P5W30} units are modified by different transition metal (TM)-organic fragments to extend the structures into three-dimensional frameworks. As nonenzymatic electrochemical sensor materials, 1-4 show good electrocatalytic activity, high sensitivity, and a low detection limit for detecting hydrogen peroxide (H2O2); 4 possesses the highest sensitivity of 195.47 µA·mM-1·cm-2 for H2O2 detection. Most importantly, the average level of H2O2 detection of these {AgP5W30}-based materials outperforms that of Na-centered Preyssler-type {NaP5W30} and most Keggin-type POM-based materials. The performances of such {AgP5W30} materials mainly stem from the unique advantage of high-negatively charged {AgP5W30} clusters together with the good synergistic effect between {AgP5W30} and TMs. This work expands on the research of high-efficiency POM-based nonenzymatic electrochemical H2O2 sensors using Ag-containing POMs with high negative charges, which is also of great theoretical and practical significance to carry out health monitoring and environmental analysis.

Altered Retinal Dopamine Levels in a Melatonin-proficient Mouse Model of Form-deprivation Myopia.

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.

High-Frequency Ultrasound for Evaluation of the Pathological Invasion Level of Extramammary Paget Disease.

OBJECTIVES: Pathological invasion level of extramammary Paget disease (EMPD) is strongly related with its risk staging, treatment, and prognosis. However, the current evaluation before treatments fails to evaluate pathological invasion level of EMPD. High-frequency ultrasound (HFUS) may play a key role to solve this problem. The purpose was to explore the performance of HFUS in the evaluation of pathological invasion level of EMPD. METHODS: Sixty pathologically proven EMPD patients were retrospectively enrolled and divided into 2 groups as follows: in situ in the epidermis (IE) (n = 42) and invasion into the dermis or subcutaneous (ID) (n = 18) groups. Clinical and HFUS features were compared between the 2 groups. RESULTS: Between the 2 groups, HFUS features (lesion shape, internal echogenicity and echotexture, surface shape, epidermal hyperechoic layer on the surface, the "pseudopod sign", and color Doppler ultrasound features) and clinical features were comparable (all P >.05). Tumor growth pattern significantly differed between the 2 groups (P <.05). Infiltration depth was significantly deeper for the ID group than the IE group (P <.05). With a cutoff value of 1.55 mm for infiltration depth, the area under the receiver operating characteristic curve was 0.833. CONCLUSIONS: HFUS features of tumor growth pattern and infiltration depth may contribute to the assessment of invasion level of EMPD.

Boron-lead multiple bonds in the PbB2O- and PbB3O2- clusters.

Despite its electron deficiency, boron can form multiple bonds with a variety of elements. However, multiple bonds between boron and main-group metal elements are relatively rare. Here we report the observation of boron-lead multiple bonds in PbB2O- and PbB3O2-, which are produced and characterized in a cluster beam. PbB2O- is found to have an open-shell linear structure, in which the bond order of B☱Pb is 2.5, while the closed-shell [Pb≡B-B≡O]2- contains a B≡Pb triple bond. PbB3O2- is shown to have a Y-shaped structure with a terminal B = Pb double bond coordinated by two boronyl ligands. Comparison between [Pb≡B-B≡O]2-/[Pb=B(B≡O)2]- and the isoelectronic [Pb≡B-C≡O]-/[Pb=B(C≡O)2]+ carbonyl counterparts further reveals transition-metal-like behaviors for the central B atoms. Additional theoretical studies show that Ge and Sn can form similar boron species as Pb, suggesting the possibilities to synthesize new compounds containing multiple boron bonds with heavy group-14 elements.

Catalpol ameliorates depressive-like behaviors in CUMS mice via oxidative stress-mediated NLRP3 inflammasome and neuroinflammation.

The purpose of the present study was to investigate whether catalpol exhibited neuroprotective effects in chronic unpredictable mild stress (CUMS) mice through oxidative stress-mediated nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin-domain-containing 3 (NLRP3) inflammasome and neuroinflammation. Deficits in behavioral tests, including open field test (OFT), forced swim test (FST), and elevated plus-maze test (EPM), were ameliorated following catalpol administration. To study the potential mechanism, western blots, quantitative real-time PCR (qRT-PCR) analysis and immunofluorescence imaging were performed on the hippocampus samples. We found that the defects of behavioral tests induced by CUMS could be reversed by the absence of NLRP3 and NLRP3 inflammasome might be involved in the antidepressant effects of catalpol on CUMS mice. Similar to the NLRP3 inflammasome, the expression of interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and inducible nitride oxide synthase (iNOS) were increased after CUMS. The current study demonstrated that catalpol possessed anti-inflammatory effect on CUMS mice and inhibited microglial polarization to the M1 phenotype. In addition, the activity of mitochondrial oxidative stress might be involved in the NLRP3 activation, which was proved by the downregulation of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cleaved IL-1ß, after the administration of mitochondrion-targeted antioxidant peptide SS31. Taken together, we provided evidence that catalpol exhibited antidepressive effects on CUMS mice possibly via the oxidative stress-mediated regulation of NLRP3 and neuroinflammation.