Brush-like Co/CoSe nanoheterostructures embedded in N-doped carbon for rechargeable Zn-air batteries.

Rational design and preparation of high-performance bifunctional oxygen electrocatalysts with effective sites and excellent mass/electron transfer structures are in demand for Zn-air batteries to overcome the sluggish oxygen reduction/evolution kinetics. Herein, a scalable and facile strategy is proposed to obtain brush-like Co/CoSe nanoheterostructures embedded in N-doped carbon catalysts with optimized active sites and hierarchical nanostructures. Systematic investigation indicates that nanoheterogeneous interfaces with appropriate composition deliver significantly improved electrochemical activity. As a result, a zinc-air battery assembled with the obtained Co/CoSe nanoheterostructures embedded in the N-doped carbon (CoSe/Co@NC-1) catalyst exhibits outstanding electrochemical performance with a peak power density of 215 mW cm-2 and excellent stability for 475 hours (2850 cycles). These results indicate that this strategy is an effective method for fabricating multicomponent and hierarchically nanostructured materials with enhanced catalytic efficiency for advanced energy devices.

Effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine on pregnancy outcomes in intrahepatic cholestasis.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes. The condition is typically marked by pruritus (itching) and elevated levels of liver enzymes and bile acids. The standard treatment for ICP has generally been ursodeoxycholic acid and ademetionine 1,4-butanedisulfonate, but the efficacy of this approach remains less than optimal. Recently, polyene phosphatidylcholine has emerged as a promising new therapeutic agent for ICP due to its potential hepatoprotective effects. AIM: To evaluate the effect of polyene phosphatidylcholine/ursodeoxycholic acid/ ademetionine 1,4-butanedisulfonate on bile acid levels, liver enzyme indices, and pregnancy outcomes in patients with ICP. METHODS: From June 2020 to June 2021, 600 patients with ICP who were diagnosed and treated at our hospital were recruited and assigned at a ratio of 1:1 via random-number table method to receive either ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate (control group, n = 300) or polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate (combined group, n = 300). Outcome measures included bile acids levels, liver enzyme indices, and pregnancy outcomes. RESULTS: Prior to treatment, no significant differences were observed between the two groups (P > 0.05). Post-treatment, patients in both groups had significantly lower pruritus scores, but the triple-drug combination group had lower scores than the dual-drug combination group (P < 0.05). The bile acid levels decreased significantly in both groups, but the decrease was more significant in the triple-drug group (P < 0.05). The triple-drug group also exhibited a greater reduction in the levels of certain liver enzymes and a lower incidence of adverse pregnancy outcomes compared to the dual-drug group (P < 0.05). CONCLUSION: Polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate effectively relieves pruritus and reduces bile acid levels and liver enzyme indices in patients with ICP, providing a positive impact on pregnancy outcome and a high safety profile. Further clinical trials are required prior to clinical application.

Antioxidant Polyphenols from Lespedeza bicolor Turcz. Honey: Anti-Inflammatory Effects on Lipopolysaccharide-Treated RAW 264.7 Macrophages.

Although the honey produced by Lespedeza bicolor Turcz. is precious because of its medicinal value, its pharmacological mechanism is still unclear. Here, its anti-inflammatory and antioxidant functions on lipopolysaccharide (LPS)-treated murine RAW 264.7 macrophages were analyzed using targeted and non-targeted metabolomics. Results showed that twelve polyphenols were identified in L. bicolor honey using UHPLC-QQQ-MS/MS. L. bicolor honey extract could scavenge the free radicals DPPH• and ABTS+ and reduce Fe3+. Furthermore, pretreatment with L. bicolor honey extract significantly decreased NO production; suppressed the expression of COX-2, IL-10, TNF-α, and iNOS; and upregulated HO-1's expression in the cells with LPS application. UHPLC-Q-TOF-MS/MS-based metabolomics results revealed that L. bicolor honey extract could protect against inflammatory damage caused by LPS through the reduced activation of sphingolipid metabolism and necroptosis pathways. These findings demonstrate that L. bicolor honey possesses excellent antioxidant and anti-inflammatory activities.

FRET-Modulated Fluorescence Lifetime-Traceable Nanocarriers for Multidrug Release Monitoring and Synergistic Therapy.

In situ monitoring multidrug release in complex cellular microenvironments is significant, and currently, it is still a great challenge. In this work, a smart nanocarrier with the capability of codelivery of small molecules and gene materials as well as with Förster resonance energy transfer (FRET)-modulated fluorescence lifetime is fabricated by integrating gold nanoparticles (the acceptor) into dual-mesoporous silica loaded with multiple drugs (the donor). Once internalized into tumor cells, in weakly acidic environments, the conformation switch of the polymer grafted on nanocarriers causes its shedding from the mesopores, triggering the release of drugs. Simultaneously, based on the strong overlap between the emission spectrum of donors and the absorption spectrum of the acceptors, any slight fluctuation of the dissociation of the drugs from nanocarriers can result in a change in the FRET-modulated lifetime signal due to the extraordinarily sensitive FRET signal to the separation distance between donors and acceptors. All these implied the potential applications of this nanoplatform in various biomedical fields that require the codelivery and real-time monitoring of multidrug-based synergistic therapy.

Study on the detection of anthrax by ICP-MS based on gold nanoparticle labeling.

BACKGROUND: In recent years, inductively coupled plasma mass spectrometry (ICP-MS) has been widely used in the field of molecular biology because of its unique advantages. Anthrax is a widespread and long-standing infectious disease, which affects and restricts people's work and life seriously. OBJECTIVE: The study goal is to develop a new method for the detection of anthrax. METHODS: A rapid, sensitive and accurate method for the detection of anthrax characteristic DNA was proposed by combing gold nanoparticles (AuNPs) and inductively coupled plasma mass spectrometry. RESULTS: The linear range of this method is 100-2500 pmol/L and the limit of detection of 16.61 pmol/L. CONCLUSION: The proposed method has numerous advantages, including simplicity of operation, high sensitivity, and specificity, which provides a new idea for the detection of anthrax. Importantly, this methodology has good potential for the detection of other biological substances such as bacteria and viruses by changing the modification sequence on the nanoparticle probe.

Solid-state self-catalyzed growth of N-doped carbon tentacles on an M(Fe, Co)Se surface for rechargeable Zn-air batteries.

A scalable and facile solid-catalyzed growth approach is reported to integrate N-doped carbon tentacles with metal selenide nanoparticles, showing great potential for mass production of non-precious metal catalysts for rechargeable Zn-air batteries.

Furan-Extended Helical Rylenes with Fjord Edge Topology and Tunable Optoelectronic Properties.

Lateral furan-expansion of polycyclic aromatics, which enables multiple O-doping and peripheral edge evolution of rylenes, is developed for the first time. Tetrafuranylperylene TPF-4CN and octafuranylquaterrylene OFQ-8CN were prepared as model compounds bearing unique fjord edge topology and helical conformations. Compared to TPF-4CN, the higher congener OFQ-8CN displays a largely red-shifted (≈333 nm) and intensified absorption band (λmax =829 nm) as well as a narrowed electrochemical band gap (≈1.08 eV) due to its pronounced π-delocalization and emerging of open-shell diradicaloid upon the increase of fjord edge length. Moreover, strong circular dichroism signals in a broad range until 900 nm are observed for open-shell chiral OFQ-8CN, owing to the excellent conformational stability of its central bis(tetraoxa[5]helicene) fragments. Our studies provide insights into the relationships between edge topologies and (chir)optoelectronic properties for this novel type of O-doped PAHs.

Kaempferol-3-O-galactoside as a marker for authenticating Lespedeza bicolor Turcz. monofloral honey.

Honey produced from Lespedeza bicolor Turcz. (L. bicolor) is highly valued and relatively rare, leading to adulterated or ersatz substitutes in the marketplace, with no reliable authentication methods available for enforcement of regulations. Here, we characterize the physicochemical parameters (water content, pH, sugar content, amylase activity, and 5-hydroxymethylfurfural content) in L. bicolor honey and palynological characteristics of L. bicolor pollen as reference for assessment of quality and monoflorality. Mass spectrometry with Orthogonal Partial Least Square Discriminant Analysis of chemical constituent data from L. bicolor, chaste, acacia, jujube, and linden honeys, all commonly sold in China, identified kaempferol-3-O-galactoside as a candidate chemical marker of L. bicolor honey. We validated this screening method and quantified kaempferol-3-O-galactoside in L. bicolor, but not other honeys, at concentrations between 90.2 and 430.1 µg/kg, with high sensitivity (LOD = 0.002 mg/kg), linearity (R2 ≥ 0.99), and recovery (90.2%-110.6%), supporting its use in authenticating L. bicolor honey.

Perylene-Based Linear Nonalternant Nanoribbons with Bright Emission and Ambipolar Redox Behavior.

Here we report stepwise solution-synthesis of linear nonalternant nanoribbons (NNRs), featuring pentagonal rings peri-fused onto the repeating perylene unit. The X-ray single-crystal structures demonstrated their π-backbones as a twisted ribbon, with the longest crystalline length of the nanoribbon up to 3.9 nm. NNRs exhibited an orange to deep-red photoluminescence even under the room light, with absolute ΦF up to 82 %, most likely due to ring-strain induced molecular stiffness. Benefiting from the enlarged size and the antiaromatic character of pentagons, all of NNRs possessed ambipolar redox properties, especially for longer nanoribbons showing multiple reversible reductions and oxidations. In addition, experimental and theoretical results indicated a ground state open-shell singlet diradicaloid for the dication of longer NNRs. Our studies reveal the intriguing nonalternant structures and physical properties of this type of nanoribbons, involving the striking effects of the multiple annulated pentagons, and also provide fundamental insights into their electronic structures.

The Association Between Lysosomal Storage Disorder Genes and Parkinson's Disease: A Large Cohort Study in Chinese Mainland Population.

Background: Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson's disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal storage disorder (LSD) genes and Chinese mainland PD. Methods: We explored the association between rare variants of 69 LSD genes and PD in 3,879 patients and 2,931 controls from Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) using next-generation sequencing, which were analyzed by using the optimized sequence kernel association test. Results: We identified the significant burden of rare putative LSD gene variants in Chinese mainland patients with PD. This association was robust in familial or sporadic early-onset patients after excluding the GBA variants but not in sporadic late-onset patients. The burden analysis of variant sets in genes of LSD subgroups revealed a suggestive significant association between variant sets in genes of sphingolipidosis deficiency disorders and familial or sporadic early-onset patients. In contrast, variant sets in genes of sphingolipidoses, mucopolysaccharidoses, and post-translational modification defect disorders were suggestively associated with sporadic late-onset patients. Then, SMPD1 and other four novel genes (i.e., GUSB, CLN6, PPT1, and SCARB2) were suggestively associated with sporadic early-onset or familial patients, whereas GALNS and NAGA were suggestively associated with late-onset patients. Conclusion: Our findings supported the association between LSD genes and PD and revealed several novel risk genes in Chinese mainland patients with PD, which confirmed the importance of lysosomal mechanisms in PD pathogenesis. Moreover, we identified the genetic heterogeneity in early-onset and late-onset of patients with PD, which may provide valuable suggestions for the treatment.

Preclinical Pharmacokinetics, Tissue Distribution, and Primary Safety Evaluation of Indo5, a Novel Selective Inhibitor of c-Met and Trks.

The compound [3-(1H-benzimidazol-2-methylene)-5-(2-methylphenylaminosulfo)-2-indolone], known as Indo5, is a novel selective inhibitor of c-Met and Trks, and it is a promising anticancer candidate against hepatocellular carcinoma (HCC). Assessing the pharmacokinetic properties, tissue distribution, and toxicity of Indo5 is critical for its medicinal evaluation. A series of sensitive and specific liquid chromatography-tandem mass spectrometry methods were developed and validated to determine the concentration of Indo5 in rat plasma and tissue homogenates. These methods were then applied to investigate the pharmacokinetics and tissue distribution of Indo5 in rats. After intravenous injection of Indo5, the maximum concentration (Cmax) and the time at which Cmax was reached (Tmax) were 1,565.3 ± 286.2 ng/ml and 1 min, respectively. After oral administration, Cmax and Tmax were 54.7 ± 10.4 ng/ml and 2.0 ± 0.48 h, respectively. We calculated the absolute oral bioavailability of Indo5 in rats to be 1.59%. Following intravenous injection, the concentrations of Indo5 in various tissues showed the following order: liver > kidney ≈ heart > lung ≈ large intestine ≈ small intestine ≈ stomach > spleen > brain ≈ testes; hence, Indo5 distributed highest in the liver and could not cross the blood-brain or blood-testes barriers. Continuous injection of Indo5 for 21 days did not lead to liver injury, considering unchanged ALT and AST levels, normal histological architecture of the liver, and normal number and frequencies of immune cells in the liver, indicating a very low toxicity of Indo5 in vivo. Collectively, our findings provide a comprehensive understanding of the biological actions of Indo5 in vivo and further support its development as an antitumor treatment for HCC patients.

Lifetime Division Multiplexing by Multilevel Encryption Algorithm.

Asymmetric, multilevel, switchable, and reversible encryption is realized by algorithm encryption, which plays an important role in encryption technology. Fluorescence lifetime encryption is currently not executed by an algorithm. It is well-known that the short fluorescence lifetime (τ1), long fluorescence lifetime (τ2), amplitude-weighted average fluorescence lifetime (τm), and intensity-weighted average fluorescence lifetime (τi) can be obtained using a double exponential fitting, and then these four lifetime parameters can be considered as four lifetime algorithms. Therefore, we propose that the acquisition of these four fluorescence lifetimes can be regarded as further dividing the lifetime by different algorithms and optimizing lifetime multiplexing. Moreover, the four lifetime algorithms of τ1, τm, τ2, and τi can be switched between each other and can be used to perform asymmetric, multilevel, and reversible lifetime encryption to effectively increase the difficulties of anticounterfeiting.

A Fluorogenic and Chromogenic Probe Distinguishes Fluoride Anions and Thiols: Implications for Discrimination of Fluoride-Containing G Series and Sulfur-Containing V Series Nerve Agents.

A coumarin-based probe, FP2, was designed for the differential detection of fluoride anions and thiols, i.e., the corresponding nucleophilic substitution products from fluorine-containing G agents and sulfur-containing V agents, thus having the potential to discriminate between these two nerve agents. FP2 with two functional reaction groups, α, ß-unsaturated ketone and silyl groups, can react selectively with fluoride anions and thiols at the µM level respectively. Intriguingly, in the THF solution, FP2 reacts with the fluoride anion but not with the thiol, whereas in the EtOH/HEPES solution, FP2 reacts with the thiol but not with the fluoride anion. As a result, FP2 can produce different fluorophores in the two detection solutions, thus displaying significant fluorescence changes. In addition, the FP2 detection system can show a significant color change from colorless to yellow within seconds when detecting fluoride anions in THF detection solutions, and from yellow to light blue when detecting thiols in EtOH/HEPES solutions, which will facilitate visual detection by emergency responders at the scene of an incident involving a nerve agent.

Photo-activated chemo-immunotherapy for metastatic cancer using a synergistic graphene nanosystem.

We developed a novel treatment strategy for metastatic cancer by synergizing photothermal therapy (PTT), chemotherapy, and immunotherapy through a nanosystem to trigger host antitumor immunity. The nanosystem was constructed by loading mitoxantrone (MTX), a chemotherapeutic agent, and SB-431542 (SB), a transforming growth factor beta (TGF-ß) inhibitor, onto reduced graphene oxide (rGO). Intratumoral administration of rGO/MTX/SB, followed by non-invasive irradiation of a near-infrared laser, destroyed local primary tumors and inhibited distant metastases in 4T1 mouse mammary tumor model, which is poorly immunogenic and highly metastatic. After treatment, 70% of the tumor-bearing mice became long-term survivors and developed a tumor type-specific immunity to resist rechallenged tumor cells. We found that rGO-based PTT provided an immunogenic antigen source, forming in situ vaccination with rGO as an immune-adjuvant. The use of SB changed the tumor microenvironment and improved the therapeutic effect of MTX-generated chemotherapy and rGO-based PTT. The immunological functions of MTX, SB, and rGO acted synergistically to induce an effective tumor vaccination, as evidenced by the increased infiltration of tumor-specific cytotoxic CD8+ T lymphocytes and decreased infiltration of regulatory T cells (Tregs) in distal tumors. Collectively, we demonstrated that rGO/MTX/SB combined with laser irradiation provided a synergistic chemo-immuno-photothermal effect against tumors by in situ vaccination and inhibition of immunosuppressive microenvironment. This unique combination embodies a promising approach to treat metastatic cancers by inducing a systemic antitumor response through a local intervention.

Classification of typical hot springs and their relationship with health in Guizhou, China.

Aim to classify typical hot springs in Guizhou, China and their relevance to health. Assessing geochemical characters of typical hot springs of Guizhou and classifying through hierarchical cluster analysis, an epidemiologic study was conducted to analyze the correlation between hot spring types and health, which showed typical hot springs in Guizhou can be divided into two types, A and B. Type A is rich in fluorine, metasilicic acid, radon components and a large number of essential elements, such as Na, that the human body needs, with trace elements, such as Cr and V, that are essential or possibly essential. Type B is rich in fluorine, metasilicate, strontium components and a large number of essential elements, Ca, Mg, and S, with trace elements, Cu, Mn, Mo, Co, and Ni, that are essential or possibly essential. These hot springs' effects on the health of those bathing in them showed both types were associated with bone and joint diseases. Having bathed in hot springs during the past year was associated with skin symptoms and bone and joint symptoms, and having bathed within the past two weeks was linked to sleep quality and levels of appetite and energy. However, differences do exist between the correlation between the two types and some chronic diseases, with Type A hot springs significantly related to cardiovascular and cerebrovascular diseases and diabetes and Type B to hypertension. This classification of Guizhou's hot springs can guide the future development and use of hot spring physiotherapy.

Photocatalytic H2 Production from Water by Metal-free Dye-sensitized TiO2 Semiconductors: The Role and Development Process of Organic Sensitizers.

The utilization of solar energy to produce hydrogen from water is showing increased importance and desirability in the field of artificial photosynthesis to produce clean and sustainable fuels. In a typical three-component dye-sensitized semiconductor system for photocatalysis, the dye sensitizer plays an essential role of energy antenna for harvesting visible light and promoting the reduction reaction to generate hydrogen. In recent decades, a lot of attention has focused on metal-free organic sensitizers, which have the advantages of low cost, high molar extinction coefficient, good modifiability and, most importantly, ability to avoid the use of noble metal ions. This Review enumerates the design strategies, specific properties and photocatalytic performances of metal-free sensitizers in the past 30 years and concludes their evolution process. The advantages of different types of metal-free sensitizers are highlighted and the instructively enlightening experiences are systematic summarized.

EDAG mediates Hsp70 nuclear localization in erythroblasts and rescues dyserythropoiesis in myelodysplastic syndrome.

During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of Hsp70 to localize to the nucleus was found in Myelodysplastic syndrome (MDS) erythroblasts and can induce dyserythropoiesis, with arrest of maturation and death of erythroblasts. However, the mechanism of the nuclear trafficking of Hsp70 in erythroblasts remains unknown. Here, we found the hematopoietic transcriptional regulator, EDAG, to be a novel binding partner of Hsp70 that forms a protein complex with Hsp70 and GATA-1 during human normal erythroid differentiation. EDAG overexpression blocked the cytoplasmic translocation of Hsp70 induced by EPO deprivation, inhibited GATA-1 degradation, thereby promoting erythroid maturation in an Hsp70-dependent manner. Furthermore, in myelodysplastic syndrome (MDS) patients with dyserythropoiesis, EDAG is dramatically down-regulated, and forced expression of EDAG has been found to restore the localization of Hsp70 in the nucleus and elevate the protein level of GATA-1 to a significant extent. In addition, EDAG rescued the dyserythropoiesis of MDS patients by increasing erythroid differentiation and decreasing cell apoptosis. This study demonstrates the molecular mechanism of Hsp70 nuclear sustaining during erythroid maturation and establishes that EDAG might be a suitable therapeutic target for dyserythropoiesis in MDS patients.

Method to improve the tunable capacity of time-resolved encoding to a xanthene dye.

Conventional organic dye encoding is limited by photo-bleaching and spectral overlap, thus restricting the number of distinguishable codes that can be used in practice. The utility of a single dye for increasing additional encoding capacity has yet to be explored. To this end, we firstly report a facile, flexible and green sustainable method to maximize the time-resolved encoding capacity of the xanthene red dye, eosin. By simply adjusting the concentration, pH and viscosity of the eosin solution, eleven distinguishable populations of fluorescence lifetimes were obtained with a short lifetime range of 1.0-3.4 ns, which in turn could increase the difficulty of duplication and provide extra high-level security protection. The results provide a facile strategy to increase the temporal multiplexing capacity, and may result in the reuse of existing organic dyes as lifetime-coded polymer microspheres in the fields of information security.

A selective c-Met and Trks inhibitor Indo5 suppresses hepatocellular carcinoma growth.

BACKGROUND: Human hepatocellular carcinoma (HCC) lacks effective curative therapy and there is an urgent need to develop a novel molecular-targeted therapy for HCC. Selective tyrosine kinase inhibitors have shown promise in treating cancers including HCC. Tyrosine kinases c-Met and Trks are potential therapeutic targets of HCC and strategies to interrupt c-Met and Trks cross-signaling may result in increased effects on HCC inhibition. METHODS: The effects of Indo5 on c-Met and Trks activity were determined with in vitro kinase activity assay, cell-based signaling pathway activation, and kinases-driven cell transformation. The in vivo anti-tumor activity was determined with xenograft mice and liver orthotopic mice models. The co-expression of c-Met and TrkB in 180 pairs of HCC and adjacent normal tissues were detected using immunohistochemical staining. RESULTS: Indo5, a novel lead compound displayed biochemical potency against both c-Met and Trks with selectivity over 13 human kinases. Indo5 abrogated HGF-induced c-Met signaling activation and BDNF/NGF-induced Trks signal activation, c-Met or TrkB-mediated cell transformation and migration. Furthermore, Indo5 significantly decreased the growth of HCC cells in xenograft mice and improved the survival of mice with liver orthotopic tumors. In addition, co-expression of c-Met and TrkB in HCC patients was a predictor of poor prognosis, and combined inhibition of c-Met and TrkB exerted a synergistic suppressive effect on HCC. CONCLUSIONS: These findings indicate that Indo5 is associated with marked suppression of c-Met and Trks co-expressing HCC, supporting its clinical development as an antitumor treatment for HCC patients with co-active c-Met and Trks signaling.

Identification and characterization of different tissues in blood vessel by multiplexed fluorescence lifetimes.

Herein, fluorescence lifetime imaging microscopy (FLIM) was used to directly measure eosin fluorescence lifetimes from H&E-stained umbilical artery, and a further utilization of eosin for high-content and multi-target analysis was proposed for the first time. Smooth muscles, collagens, and elastic fibers can be distinguished by eosin fluorescence lifetimes (P < 0.001). Erythrocytes, smooth muscles, elastic fibers, and type I and III collagen from the H&E-stained umbilical artery can be simultaneously identified by multiplexed fluorescence lifetimes of eosin. Use of eosin and lifetime-based separation is a potential method to simplify the special staining for clinicopathologic examination. Multiplexed eosin fluorescence lifetimes may be a newly developed method that can directly determine the relative content of elastic fiber and collagens from the H&E-stained sections. FLIM may have potential applications as an assisted tool in the assessment of the severity and complexity of cardiovascular diseases.