A Small-Molecule Ratiometric Photoacoustic Probe for the High-Spatiotemporal-Resolution Imaging of Copper(II) Dynamics in the Mouse Brain.

Copper dysmetabolism is associated with various neurodegenerative disorders, making high-spatiotemporal-resolution imaging of Cu2+ in the brain essential for understanding the underlying pathophysiological processes. Nevertheless, the current probes encounter obstacles in crossing the blood-brain barrier (BBB) and providing high-spatial-resolution in deep tissues. Herein, we present a photoacoustic probe capable of imaging Cu2+ dynamics in the mouse brain with high-spatiotemporal-resolution. The probe demonstrates selective ratiometric and reversible responses to Cu2+ , while also efficiently crossing the BBB. Using the probe as the imaging agent, we successfully visualized Cu2+ in the brain of Parkinson's disease (PD) model mouse with a remarkable micron-level resolution. The imaging results revealed a significant increase in Cu2+ levels in the cerebral cortex as PD progresses, highlighting the close association between Cu2+ alternations in the region and the disease. We also demonstrated that the probe can be used to monitor changes in Cu2+ distribution in the PD model mouse brain during L-dopa intervention. Mechanism studies suggest that the copper dyshomeostasis in the PD mouse brain was dominated by the expression levels of divalent metal transporter 1. The application of our probe in imaging Cu2+ dynamics in the mouse brain offers valuable insights into the copper-related molecular mechanisms underlying neurodegenerative diseases.

A NIR-II Photoacoustic Probe for High Spatial Quantitative Imaging of Tumor Nitric Oxide in Vivo.

Nitric oxide (NO) exhibits both pro- and anti-tumor effects. Therefore, real-time in vivo imaging and quantification of tumor NO dynamics are essential for understanding the conflicting roles of NO played in pathophysiology. The current molecular probes, however, cannot provide high-resolution imaging in deep tissues, making them unsuitable for these purposes. Herein, we designed a photoacoustic probe with an absorption maximum beyond 1000 nm for high spatial quantitative imaging of in vivo tumor NO dynamics. The probe exhibits remarkable sensitivity, selective ratiometric response behavior, and good tumor-targeting abilities, facilitating ratiometric imaging of tumor NO throughout tumor progression in a micron-resolution level. Using the probe as the imaging agent, we successfully quantified NO dynamics in tumor, liver and kidney. We have pinpointed an essential concentration threshold of around 80 nmol/cm3 for NO, which plays a crucial role in the "double-edged-sword" function of NO in tumors. Furthermore, we revealed a reciprocal relationship between the NO concentration in tumors and that in the liver, providing initial insights into the possible NO-mediated communication between tumor and the liver. We believe that the probe will help resolve conflicting aspects of NO biology and guide the design of imaging agents for tumor diagnosis and anti-cancer drug screening.

Blood-Brain Barrier Permeable Photoacoustic Probe for High-Resolution Imaging of Nitric Oxide in the Living Mouse Brain.

Alternations in the brain nitric oxide (NO) homeostasis are associated with a variety of neurodegeneration diseases; therefore, high-resolution imaging of NO in the brain is essential for understanding pathophysiological processes. However, currently available NO probes are unsuitable for this purpose due to their poor ability to cross the blood-brain barrier (BBB) or to image in deep tissues with spatial resolution. Herein, we developed a photoacoustic (PA) probe with BBB crossing ability to overcome this obstacle. The probe shows a highly selective ratiometric response toward NO, which enables the probe to image NO with micron resolution in the whole brain of living mice. Using three-dimensional PA imaging, we demonstrated that the probe could be used to visualize the detailed NO distribution in varying depth cross-sections (0-8 mm) of the living Parkinson's disease (PD) mouse brain. We also investigated the therapeutic properties of natural polyphenols in the PD mouse brain using the probe as an imaging agent and suggested the potential of the probe for screening therapeutic agents. This study provides a promising imaging agent for imaging of NO in the mouse brain with high resolution. We anticipate that these findings may open up new possibilities for understanding the biological functions of NO in the brain and the development of new imaging agents for the diagnosis and treatment of brain diseases.

A Photoacoustic Probe with Blood-Brain Barrier Crossing Ability for Imaging Oxidative Stress Dynamics in the Mouse Brain.

Spatiotemporal assessment of the oxidative stress dynamics in the brain is crucial for understanding the molecular mechanism underlying neurodegenerative diseases. However, existing oxidative stress probes have poor blood-brain barrier permeability or poor penetration depth, making them unsuitable for brain imaging. Herein, we developed a photoacoustic probe that enables real-time imaging of oxidative stress dynamics in the mouse brain. The probe not only responds to oxidative stress in a reversible and ratiometric manner, but it can also cross the blood-brain barrier of the mouse brain. Notably, the probe displayed excellent photoacoustic imaging of oxidative stress dynamics in the brains of Parkinson's disease mouse models. In addition, we investigated the antioxidant properties of natural polyphenols in the brain of a Parkinson's disease mouse model using the probe as an imaging agent and suggested the potential of the probe for screening anti-oxidative stress agents.

Facile Controlled Synthesis of Pd-ZnO Nanostructures for Nitrite Detection.

The electrocatalytic characteristics of nanostructures are significantly affected by surface structure. The strict regulation of structural characteristics is highly beneficial for the creation of novel nanocatalysts with enhanced electrocatalytic performance. This work reports a nitrite electrochemical sensor based on novel flower-like Pd-ZnO nanostructures. The Pd-ZnO nanocatalysts were synthesized through a simple hydrothermal method, and their morphology and structure were characterized via field-emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). Their electrocatalytical performance in the nitrite oxidation reaction was studied via cyclic voltammetry (CV) and the amperometric technique. Compared to pure ZnO and Pd nanoparticles, the Pd-ZnO nanostructures exhibited enhanced electrochemical performance in the nitrite oxidation reaction. In order to investigate the relationships between the structures of Pd-ZnO nanocatalysts and the corresponding electrocatalytic performances, different surface morphologies of Pd-ZnO nanocatalysts were fabricated by altering the solution pH. It was found that the flower-like Pd-ZnO nanostructures possessed larger effective surface areas and faster electron transfer rates, resulting in the highest electrocatalytic performance in the nitrite oxidation reaction. The designed nitrite sensor based on flower-like Pd-ZnO displayed a wide concentration linear range of 1 µM-2350 µM, a low detection limit of 0.2 µM (S/N of 3), and high sensitivity of 151.9 µA mM-1 cm-2. Furthermore, the proposed sensor exhibited perfect selectivity, excellent reproducibility, and long-time stability, as well as good performance in real sample detection.

A Cyclen-Functionalized Cobalt-Substituted Sandwich-Type Tungstoarsenate with Versatility in Removal of Methylene Blue and Anti-ROS-Sensitive Tumor Cells.

Oxidative degradation by using reactive oxygen species (ROS) is an effective method to treat pollutants. The synthesis of artificial oxidase for the degradation of dyes is a hot spot in molecular science. In this study, a nanoscale sandwich-type polyoxometalate (POM) on the basis of a tetra-nuclear cobalt cluster and trivacant B-α-Keggin-type tungstoarsenate {[Co(C8H20N4)]4}{Co4(H2O)2[HAsW9O34]2}∙4H2O (abbreviated as CAW, C8H20N4 = cyclen) has been synthesized and structurally examined by infrared (IR) spectrum, ultraviolet-visible (UV-Vis) spectrum, X-ray photoelectron spectrum (XPS), single-crystal X-ray diffraction (SXRD), and bond valence sum (Σs) calculation. According to the structural analysis, the principal element of the CAW is derived from modifying sandwich-type polyanion {Co4(H2O)2 [HAsW9O34]2}8- with four [Co(Cyclen)]2+, in which 1,4,7,10-tetraazacyclododecane (cyclen) is firstly applied to modify POM. It is also demonstrated that CAW is capable of efficiently catalyzing the production of ROS by the synergistic effects of POM fragments and Co-cyclen complexes. Moreover, CAW can interfere with the morphology and proliferation of sensitive cells by producing ROS and exhibits ability in specifically eliminating methylene blue (MB) dyes from the solution system by both adsorption and catalytic oxidation.

H-Bonding Room Temperature Phosphorescence Materials via Facile Preparation for Water-Stimulated Photoluminescent Ink.

Pure organic room-temperature phosphorescence (RTP) materials built upon noncovalent interactions have attracted much attention because of their high efficiency, long lifetime, and stimulus-responsive behavior. However, there are limited reports of noncovalent RTP materials because of the lack of specific design principles and clear mechanisms. Here, we report on a noncovalent material prepared via facile grinding that can emit fluorescence and RTP emission differing from their components' photoluminescent behavior. Exciplex can be formed during the preparation process to act as the minimum emission unit. We found that H-bonds in the RTP system provide restriction to nonradiative transition but also enhance energy transformation and energy level degeneracy in the system. Moreover, water-stimulated photoluminescent ink is produced from the materials to achieve double-encryption application with good resolution.

Activity-Based Fluorescent Molecular Logic Gate Probe for Dynamic Tracking of Mitophagy Induced by Oxidative Stress.

Visualizing and modulating the mitophagy process is essential for understanding the role of mitophagy in cellular homeostasis, physiology, and pathology. To overcome the sensing limitation of available mitophagy probes to only lysosome fusion or degradation, a molecular logic gate probe showing multiple fluorescence responses to different mitophagy stages was proposed in this study to sense the oxidative stress-induced mitophagy via a dual-channel mode. This new fluorescent molecular logic gate probe, Mito-PN, was composed by integrating a peroxynitrite-responsive 1,8-naphthalimide with an acidity-activatable rhodamine spirolactam and possesses the mitochondria-targeting capability due to its triphenylphosphonium group. This probe is able to sense both the mitophagy initiation triggered by peroxynitrite and lysosome fusion at different fluorescence wavelengths. It can be rapidly activated by mitochondrial peroxynitrite to turn on the green fluorescence of naphthalimide, and subsequent lysosome/mitophagosome fusion activates the probe with protons to generate red fluorescence. Moreover, our preliminary results demonstrate that the fluorescence response of Mito-PN to peroxynitrite-induced mitophagy can be discriminated from the mitophagy stimulated by carbonyl cyanide m-chlorophenyl hydrazone, which further proves the specific mitophagy tracking ability of Mito-PN. Overall, this research offers a potentially powerful tool for studying the role played by peroxynitrite in mitophagy and provides a versatile strategy for monitoring oxidative stress-related pathological processes.

Tracking Labile Copper Fluctuation In Vivo/Ex Vivo: Design and Application of a Ratiometric Near-Infrared Fluorophore Derived from 4-Aminostyrene-Conjugated Boron Dipyrromethene.

Specimen differences, tissue-dependent background fluorescence and scattering, and deviated specimen position and sensor concentration make optical imaging for labile copper fluctuation in animals questionable, and a signal comparison between specimens is infeasible. We proposed ratiometric optical imaging as an alternative to overcome these disadvantages, and a near-infrared (NIR) ratiometric sensor, BDPS1, was devised therefore by conjugating boron dipyrromethene (BODIPY) with 4-aminostyrene and modifying the 4-amino group as a Cu+ chelator. BDPS1 possessed an excitation ratiometric copper-sensing ability to show the ratio of NIR emission (710 nm) upon excitation at 600 nm to that at 660 nm, Fex600/Fex660, increasing from 2.8 to 10.7. This sensor displayed still the opposite copper response of its internal charge transfer (ICT; 670 nm) and local (581 nm) emission bands. Ratiometric imaging with this sensor disclosed a higher labile copper region near the nucleus apparatus, and HEK-293T cells were more sensitive to copper incubation than MCF-7 cells. Dual excitation ratiometric imaging with this sensor realized tracking of labile copper fluctuation in mice, and the whole-body imaging found that tail intravenous injection of CUTX-101, a therapeutical agent for Menkes disease, led to a distinct labile copper increase in the upper belly. The ex vivo imaging of the resected viscera of mice revealed that CUTX-101 injection enhanced the labile copper level in the liver, intestine, lung, and gall bladder in sequence, yet the kidney, heart, and spleen showed almost no response. This study indicated that modifying BODIPY as an extended ICT fluorophore, with its electron-donating group being derived as a metal chelator, is an effective design rationale of NIR ratiometric sensors for copper tracking in vivo/ex vivo.

Antioxidant Activity Evaluation of Oviductus Ranae Protein Hydrolyzed by Different Proteases.

As nutrition and a health tonic for both medicine and food, the protein content of Oviductus Ranae is more than 40%, making it an ideal source to produce antioxidant peptides. This work evaluated the effects of six different proteases (pepsin, trypsin, papain, flavourzyme, neutral protease and alcalase) on the antioxidant activity of Oviductus Ranae protein, and analyzed the relationship between the hydrolysis time, the degree of hydrolysis (DH) and the antioxidant activity of the enzymatic hydrolysates. The results showed that the antioxidant activity of Oviductus Ranae protein was significantly improved and the optimal hydrolysis time was maintained between 3-4 h under the action of different proteases. Among them, the protein hydrolysate which was hydrolyzed by pepsin for 180 min had the strongest comprehensive antioxidant activity and was most suitable for the production of antioxidant peptides. At this time, the DH, the DPPH radical scavenging activity, the absorbance value of reducing power determination and the hydroxyl radical scavenging activity corresponding to the enzymatic hydrolysate were 13.32 ± 0.24%, 70.63 ± 1.53%, 0.376 ± 0.009 and 31.96 ± 0.78%, respectively. Correlation analysis showed that there was a significant positive correlation between the hydrolysis time, the DH and the antioxidant activity of the enzymatic hydrolysates, further indicating that the hydrolysates of Oviductus Ranae protein had great antioxidant potential. The traditional anti-aging efficacy of Oviductus Ranae is closely related to the scavenging of reactive oxygen species, and its hydrolysates have better antioxidant capacity, which also provides support for further development of its traditional anti-aging efficacy.

A Borondifluoride-Complex-Based Photothermal Agent with an 80 % Photothermal Conversion Efficiency for Photothermal Therapy in the NIR-II Window.

Small organic photothermal agents (SOPTAs) that absorb in the second near-infrared (NIR-II, 1000-1700 nm) window are highly desirable in photothermal therapy for their good biocompatibility and deeper tissue penetration. However, the design of NIR-II absorbing SOPTAs remains a great challenge. Herein, we report that molecular engineering of BF2 complex via strengthening the donor-acceptor conjugation and increasing the intramolecular motions is an efficient strategy to achieve NIR-II absorbing SOPTAs with high photothermal performance. Based on this strategy, a BF2 complex, BAF4, was designed and synthesized. BAF4 exhibits an intense absorption maximum at 1000 nm and negligible fluorescence. Notably, the nanoparticles of BAF4 achieve a high photothermal conversion efficiency value of 80 % under 1064 nm laser irradiation (0.75 W cm-2 ). In vitro and in vivo studies reveal the great potential of BAF4 nanoparticles in photoacoustic imaging-guided photothermal therapy in the NIR-II window.

Ubiquitin S65 phosphorylation engenders a pH-sensitive conformational switch.

Ubiquitin (Ub) is an important signaling protein. Recent studies have shown that Ub can be enzymatically phosphorylated at S65, and that the resulting pUb exhibits two conformational states-a relaxed state and a retracted state. However, crystallization efforts have yielded only the structure for the relaxed state, which was found similar to that of unmodified Ub. Here we present the solution structures of pUb in both states obtained through refinement against state-specific NMR restraints. We show that the retracted state differs from the relaxed state by the retraction of the last ß-strand and by the extension of the second α-helix. Further, we show that at 7.2, the pKa value for the phosphoryl group in the relaxed state is higher by 1.4 units than that in the retracted state. Consequently, pUb exists in equilibrium between protonated and deprotonated forms and between retracted and relaxed states, with protonated/relaxed species enriched at slightly acidic pH and deprotonated/retracted species enriched at slightly basic pH. The heterogeneity of pUb explains the inability of phosphomimetic mutants to fully mimic pUb. The pH-sensitive conformational switch is likely preserved for polyubiquitin, as single-molecule FRET data indicate that pH change leads to quaternary rearrangement of a phosphorylated K63-linked diubiquitin. Because cellular pH varies among compartments and changes upon pathophysiological insults, our finding suggests that pH and Ub phosphorylation confer additional target specificities and enable an additional layer of modulation for Ub signals.

An Optical/Photoacoustic Dual-Modality Probe: Ratiometric in/ex Vivo Imaging for Stimulated H2S Upregulation in Mice.

Tracking signaling H2S in live mice demands responsive imaging with fine tissue imaging depth and low interferences from tissue scattering/autofluorescence and probe concentration. With complementary advantages of fluorescence and photoacoustic (PA) imaging, optical/PA dual-modality imaging was suggested for in/ex vivo H2S imaging. Therefore, a meso-benzoyloxyltricarboheptamethine cyanine, HS-CyBz, was prepared as the first ratiometric optical/PA dual-modality probe for H2S, profiting from a keto-enol transition sensing mechanism. Tail intravenous injection of this probe leads to probe accumulation in the liver of mice, and the endogenous H2S upregulation triggered by S-adenosyl-l-methionine has been verified by ratiometric optical/PA imaging, suggesting the promising potential of this ratiometric dual-modality imaging.

Phosphorescence Lifetime Imaging of Labile Zn2+ in Mitochondria via a Phosphorescent Iridium(III) Complex.

Phosphorescence lifetime Zn2+ imaging possesses the advantage over normal fluorescence imaging in offering the more accurate temporal-spatial Zn2+ information. Herein, we report a new phosphorescent cyclometalated Ir(III) complex with a Zn2+-chelator bearing 1,10-phenanthrolin acting as ancillary ligand, Zin-IrDPA, which displays the specific Zn2+-induced enhancement of phosphorescence and phosphorescence lifetime, and the mitochondria-targeting ability. Moreover, its Zn2+-induced phosphorescence lifetime enhancement factor is not affected by medium lipophilicity, viscosity, polarity, and especially ambient oxygen. The reversible tracking of introduced exogenous labile Zn2+ in MCF-7 and HeLa cells via phosphorescence imaging and phosphorescence lifetime imaging (PLIM) have been realized with Zin-IrDPA. Moreover, PLIM with Zin-IrDPA is able to track the SNOC-stimulated endogenous Zn2+ release in mitochondria.

A Potential Bone-Targeting Hypotoxic Platinum(II) Complex with an Unusual Cytostatic Mechanism toward Osteosarcoma Cells.

Osteosarcoma (OS) is the most common primary pediatric bone tumor lethal to children and adolescents. Chemotherapeutic agents such as cisplatin are not effective for OS because of their poor accessibility to this cancer and severe systemic toxicity. In this study, a lipophilic platinum(II) complex bearing a bisphosphonate bone-targeting moiety, cis-[PtL(NH3)2Cl]NO3 {BPP; L = tetraethyl [2-(pyridin-2-yl)ethane-1,1-diyl]bisphosphonate}, was prepared and characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray crystallography. The cytotoxicity of BPP toward OS cell lines U2OS and MG-63 was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. BPP exhibits moderate inhibition against U2OS cells through a mechanism involving both DNA binding and a mevalonate pathway. The acute toxicity of BPP to mice is 7-fold lower than that of cisplatin. The relative low systemic toxicity may result from the steric hindrance of the ligand, which blocks BPP approaching the bases of DNA. The results suggest that incorporating bisphosphonates into a platinum complex not only enhances its bone-targeting property but also minimizes its reactivity toward DNA and thereby lowers the systematic toxicity of the complex. The diminished cytotoxicity of BPP could be compensated for by increasing the therapeutic dose with marginal harm. This strategy provides a new possibility for overcoming the ineffectiveness and systemic toxicity of platinum drugs in the treatment of OS.

Modulating Conformation of Aß-Peptide: An Effective Way to Prevent Protein-Misfolding Disease.

Alzheimer's disease (AD) is a typical protein-misfolding disease. Aggregation of amyloid ß-peptide (Aß) plays a key role in the etiology of AD. The misfolding of Aß results in the formation of ß-sheet-rich aggregates and damages the function of neurons. A modified polyoxometalate (POM), [CoL(H2O)]2[CoL]2[HAsVMoV6MoVI6O40] [CAM, L = 2-(1 H-pyrazol-3-yl)pyridine], was designed to disaggregate the Aß aggregates, where L acts as an Aß-targeting group and POM as a conformational modulator. X-ray crystallography shows that CAM is composed of a ε-Keggin unit and four coordination units. CAM can disaggregate the ß-sheet-rich fibrils and metal-induced or self-aggregated Aß aggregates, and it further inhibits the production of ROS; as a result, it can protect the neurons from synaptic toxicity induced by Zn2+- or Cu2+-Aß aggregates or Aß self-aggregation. The mechanism of disaggregation involves a transformation of Aß conformation from ß-sheet to other conformers. The nature of the process is an interference of the ß-sheet conformation by CAM via hydrogen bonding. CAM specifically interacts with Aß aggregates but does not disturb the cerebral metal homeostasis and enzymatic systems. Molecular simulation suggests that the appropriate size of CAM and the cavity of ß-sheets facilitate the interaction between CAM and Aß aggregates; additionally, the H-bonding-favored amino acid residues in the cavity provide a precondition for the interaction. Moreover, CAM is lipophilic and capable of penetrating the blood-brain barrier, and it is metabolizable without causing an untoward effect to mice at high dosages. In view of the significant inhibitory effect on the Aß aggregation and related neurotoxicity, CAM represents a new type of leading compounds with a distinctive mechanism of action for the treatment of Alzheimer' disease. The conception of this study may be applied to other protein-misfolding diseases caused by conformational changes.

Factors impacting the use of antenatal care and hospital child delivery services: a case study of rural residents in the Enshi Autonomous Prefecture, Hubei Province, China.

This study was undertaken to understand the factors that impact whether rural women obtain antenatal care (ANC) and choose to use hospital delivery services in central and western China. We chose to conduct field research with the rural residents in Hubei Province through a combination of random sampling and purposive sampling methods. A mixed method approach was taken to analyze the factors impacting the use of ANC and hospital delivery services from the perspective of the villagers. Our results indicate that the quality of the available ANC services is poor. In particular, women who have special circumstances and unplanned pregnancies or who become pregnant prior to marriage are confronted with inadequate ANC and hospital child delivery services. The factors that impact whether women use or not use ANC and hospital delivery services and that cause women to choose hospital or home delivery can be understood at three levels: macro, middle, and micro. We strongly suggest that the policies and projects that promote maternal healthcare in rural areas be sustained with an added focus on including women with special circumstances. Village doctors can be enlisted to regularly visit pregnant women at home and to provide extra explanation about the ANC services available and the purpose of maternal healthcare. These findings and suggestions can be used by local health providers and decision-makers to improve the quality of ANC and hospital delivery services.

Differential efficacy of two small molecule PHLPP inhibitors to promote nucleus Pulposus cell health.

Background: Intervertebral disc (IVD) degeneration is associated with chronic back pain. We previously demonstrated that the phosphatase pleckstrin homology domain and leucine-rich repeat protein phosphatase (PHLPP) 1 was positively correlated with IVD degeneration and its deficiency decelerated IVD degeneration in both mouse IVDs and human nucleus pulposus (NP) cells. Small molecule PHLPP inhibitors may offer a translatable method to alleviate IVD degeneration. In this study, we tested the effectiveness of the two PHLPP inhibitors NSC117079 and NSC45586 in promoting a healthy NP phenotype. Methods: Tail IVDs of 5-month-old wildtype mice were collected and treated with NSC117079 or NSC45586 under low serum conditions ex vivo. Hematoxylin & eosin staining was performed to examine IVD structure and NP cell morphology. The expression of KRT19 was analyzed through immunohistochemistry. Cell apoptosis was assessed by TUNEL assay. Human NP cells were obtained from patients with IVD degeneration. The gene expression of KRT19, ACAN, SOX9, and MMP13 was analyzed via real time qPCR, and AKT phosphorylation and the protein expression of FOXO1 was analyzed via immunoblot. Results: In a mouse IVD organ culture model, NSC45586, but not NSC117079, preserved vacuolated notochordal cell morphology and KRT19 expression while suppressing cell apoptosis, counteracting the degenerative changes induced by serum deprivation, especially in males. Likewise, in degenerated human NP cells, NSC45586 increased cell viability and the expression of KRT19, ACAN, and SOX9 and reducing the expression of MMP13, while NSC117079 treatment only increased KRT19 expression. Mechanistically, NSC45586 treatment increased FOXO1 protein expression in NP cells, and inhibiting FOXO1 offset NSC45586-induced regenerative potential, especially in males. Conclusions: Our study indicates that NSC45586 was effective in promoting NP cell health, especially in males, suggesting that PHLPP plays a key role in NP cell homeostasis and that NSC45586 might be a potential drug candidate in treating IVD degeneration.

Changes and Determinants of Maternal Health Services Utilization in Ethnic Minority Rural Areas in Central China, 1991-2015: An Ecological Systems Theory Perspective.

BACKGROUND: Universal maternal health coverage is a proven, effective strategy for maternal survival. This study aimed to describe the changes and determinants of maternal health service use between 1991 and 2015 in central China. METHODS: The study was conducted in Enshi Prefecture. Women were eligible for inclusion if they were rural women who lived in villages, had live births during 1991-2015, could recall their maternal care histories, and had no communication problems. This retrospective study included 470 rural women in 9 villages and collected 770 records. The conceptual framework was designed based on the Society Ecosystem Theory. The determinants included micro-factors (individual characteristics), meso-factors (family factors, community factors, healthcare factors), and macro-factors (government-run maternal and child health programs, abbreviated as MCH programs). Multivariate logistic regressions were applied to analyze the determinants of maternal health service utilization. RESULTS: The utilization of maternal healthcare has improved in Enshi. The hospital birth rate was 98.1% in 2009 and mostly 100% in subsequent years. The prenatal examination rate, the postpartum visit rate, and the continuum of maternal health service (CMHS) rate increased to 73.3%, 67.7%, and 53.4%, respectively, in 2009-2015. The utilization of maternal health services was affected by macro-factors, meso-factors, and micro-factors, with macro-factors being the most notable contributors. CONCLUSIONS: Despite the remarkable improvements in antenatal care (ANC) use and hospital birth, gaps in postpartum visits remain. Promoting the integrated continuum of maternal and child healthcare in ethnic minority rural areas requires the joint efforts of the government, health and other sectors, communities, families, and individuals.

Fluorescent phenothiazine-fused boron complexes for ratiometric hypochlorite imaging.

Fluorescent hypochlorite probes with ratiometric imaging ability are highly desirable for imaging hypochlorite in biological systems. However, it is still challenging to develop new scaffolds for these probes. In this study, we demonstrate that phenothiazine-fused boron complexes are promising scaffolds for the design of ratiometric fluorescent hypochlorite probes. The synthesized complexes based on the scaffold show ultrafast and ratiometric absorption/fluorescence changes for hypochlorite. We also developed an endoplasmic reticulum-targeting probe and demonstrated that it has excellent real-time imaging ability for both endogenous and exogenous hypochlorite in the endoplasmic reticulum of living cells.