Poly(ethylene oxide)- and Polyzwitterion-Based Thermoplastic Elastomers for Solid Electrolytes.

In this article, ABA triblock copolymer (tri-BCP) thermoplastic elastomers with poly(ethylene oxide) (PEO) middle block and polyzwitterionic poly(4-vinylpyridine) propane-1-sulfonate (PVPS) outer blocks were synthesized. The PVPS-b-PEO-b-PVPS tri-BCPs were doped with lithium bis-(trifluoromethane-sulfonyl) imide (LiTFSI) and used as solid polyelectrolytes (SPEs). The thermal properties and microphase separation behavior of the tri-BCP/LiTFSI hybrids were studied. Small-angle X-ray scattering (SAXS) results revealed that all tri-BCPs formed asymmetric lamellar structures in the range of PVPS volume fractions from 12.9% to 26.1%. The microphase separation strength was enhanced with increasing the PVPS fraction (fPVPS) but was weakened as the doping ratio increased, which affected the thermal properties of the hybrids, such as melting temperature and glass transition temperature, to some extent. As compared with the PEO/LiTFSI hybrids, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids could achieve both higher modulus and higher ionic conductivity, which were attributed to the physical crosslinking and the assistance in dissociation of Li+ ions by the PVPS blocks, respectively. On the basis of excellent electrical and mechanical performances, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids can potentially be used as solid electrolytes in lithium-ion batteries.

Does it reasonable to include grid-side energy storage costs in transmission and distribution tariffs? Benefit evaluation based on economic externality.

Grid-side energy storage has become a crucial part of contemporary power systems as a result of the rapid expansion of renewable energy sources and the rising demand for grid stability. This study aims to investigate the rationality of incorporating grid-side energy storage costs into transmission and distribution (T&D) tariffs, evaluating this approach using economic externality theory. We first develop a comprehensive benefit evaluation framework based on economic externality theory considering system stability, renewable energy integration, end-user, and environmental impacts. Then, using the CPLEX solver, an operating model of grid-side energy storage is constructed with the goal of reducing substation load variations. Through a case study, it is found that grid-side energy storage has significant positive externality benefits, validating the rationale for including grid-side energy storage costs in T&D tariffs. Sensitivity analysis suggests that with cost reduction and market development, the proportion of grid-side energy storage included in the T&D tariff should gradually recede. As a result, this study offers important information about whether it is reasonable to include grid-side energy storage costs in T&D tariffs in China.

Effectiveness and safety of community-led assisted partner service among HIV-diagnosed men who have sex with men: a multicentre, randomized controlled trial in China.

Background: No randomized controlled trials have involved established HIV-diagnosed men who have sex with men (MSM) diagnosed for more than 6 months into the assisted partner service (aPS). We compared voluntary aPS involving community-based organizations (CBOs) and HIV self-testing (aPSST) with regular partner service (rPS) in HIV-diagnosed MSM irrespective of diagnosis time. Methods: In this unblinded, multicentre trial, we enrolled HIV-diagnosed MSM irrespective of diagnosis time in three cities in northern China. Index patients were randomly assigned to aPSST or rPS. Index patients in the aPSST group were additionally provided a comprehensive intervention package including HIV self-testing and CBO-based aPS compared with rPS group. The primary outcome was the number of index patients whose any sexual partner tested for HIV during the 6-month study. Completion of HIV testing was defined as sexual partners taking a clinic-based HIV test or HIV self-testing. Safety was assessed preliminary at the end of the 6-month follow-up. This study has been registered at chictr.org.cn (ChiCTR2000038784). Findings: From March to December 2021, 325 of HIV-diagnosed MSM were enrolled (90⋅2% were established HIV-diagnosed MSM) and randomly assigned to receive aPSST (n = 167) or rPS (n = 158). At 6 months, 110 (65⋅9%) index patients in the aPSST group had at least one sexual partner tested for HIV compared with 50 (31⋅6%) in the rPS group (hazard ratio 2⋅86; 95% confidence interval 2⋅03-4⋅03; p < 0⋅001). No significant difference was observed in effects of aPSST on HIV testing promotion between established and newly HIV-diagnosed MSM. Self-reported harms were infrequently observed in both groups (approximately 2⋅0%). Interpretation: Among HIV-diagnosed MSM regardless of diagnosis time, voluntary aPS involving CBOs and HIV self-testing was effective and safe for promoting partner HIV testing. Funding: This work was supported by the Mega-Projects of National Science Research, the National Natural Science Foundation of China and the Liaoning Revitalization Talents Program, China.

Overexpression of sirtuin 1 attenuates calcium oxalate-induced kidney injury by promoting macrophage polarization.

Sirtuin 1 (SIRT1) protein is involved in macrophage differentiation, while NOTCH signaling affects inflammation and macrophage polarization. Inflammation and macrophage infiltration are typical processes that accompany kidney stone formation. However, the role and mechanism of SIRT1 in renal tubular epithelial cell injury caused by calcium oxalate (CaOx) deposition and the relationship between SIRT1 and the NOTCH signaling pathway in this urological disorder are unclear. This study investigated whether SIRT1 promotes macrophage polarization to inhibit CaOx crystal deposition and reduce renal tubular epithelial cell injury. Public single-cell sequencing data, RT-qPCR, immunostaining approaches, and Western blotting showed decreased SIRT1 expression in macrophages treated with CaOx or exposed to kidney stones. Macrophages overexpressing SIRT1 differentiated towards the anti-inflammatory M2 phenotype, significantly inhibiting apoptosis and alleviating injury in the kidneys of mice with hyperoxaluria. Conversely, decreased SIRT1 expression in CaOx-treated macrophages triggered Notch signaling pathway activation, promoting macrophage polarization towards the pro-inflammatory M1 phenotype. Our results suggest that SIRT1 promotes macrophage polarization towards the M2 phenotype by repressing the NOTCH signaling pathway, which reduces CaOx crystal deposition, apoptosis, and damage in the kidney. Therefore, we propose SIRT1 as a potential target for preventing disease progression in patients with kidney stones.

Electrostatic crosslinking-enabled highly asymmetric lamellar nanostructures of polyzwitterionic block copolymers for lithography.

For the bulk self-assembly of traditional diblock copolymers (di-BCPs), lamellar structures only occur when two constituents have similar volume fractions (f) and two alternating layers tend to have similar thicknesses. Highly asymmetric lamellar (A-LAM) structures, in which the thickness of one layer is several times higher than the other, are hardly formed in di-BCPs, while they have potential applications in nanolithography. In this work, A-LAM structures with different dimensions were constructed using a type of simple linear di-BCP, polystyrene-b-poly(4-vinylpyridine)propane-1-sulfonate (PS-b-PVPS) with the polyzwitterionic block PVPS in minority. The origin of the A-LAM structure was ascribed to the electrostatic crosslinking and confirmed by doping PS-b-PVPS block copolymers (BCPs) with N-butyl pyridinium methane sulfonate (BPMS). The morphology of compositionally asymmetric PS-b-PVPS BCPs changed from A-LAM to cylindrical structures upon salt-doping, i.e. the phase behavior of common BCPs was recovered. In addition, the morphologies of PS-b-PVPS BCPs with similar molecular weights but varied compositions were also studied, and only two kinds of structures (lamellar or ill-defined spherical structure) were observed when the volume fraction of PVPS (fPVPS) was less than 0.5, and the composition range for the formation of the lamellar structure was found to be fPVPS ≥ 0.188.

PEO-Based Block Copolymer Electrolytes Containing Double Conductive Phases with Improved Mechanical and Electrochemical Properties.

In this work, the advanced all solid-state block copolymer electrolytes (SBCPEs) for lithium-ion batteries with double conductive phases, poly(ethylene oxide)-b-poly(trimethyl-N-((2-(dimethylamino)ethyl methacrylate)-7-propyl)-ammonium bis(trifluoromethanesulfonyl) imide) (PEO-b-PDM-dTFSI)/LiTFSI, were fabricated, in which the charged PDM-dTFSI block contained double quaternary ammonium cations and the PEO block was doped with LiTFSI. The disordered (DIS) and ordered lamellae (LAM) phase structures were achieved by adjusting the composition of the block copolymer and the doping ratio r. In addition, the presence of the hard PDM-dTFSI block and the formation of the LAM phase structure resulted in a good mechanical strength of the solid PEO-b-PDM-dTFSI/LiTFSI electrolyte, and it could maintain a high level of 104 Pa at 100 °C, which was around 10,000 times stronger than that of the PEO/LiTFSI electrolyte. Based on the good mechanical and electrochemical properties, the PEO-b-PDM-dTFSI/LiTFSI SBCPE exhibited excellent long-term galvanostatic cycle performance, indicating the strong ability to suppress lithium dendrites.

Spatial Transcriptomic Analysis Reveals Associations between Genes and Cellular Topology in Breast and Prostate Cancers.

BACKGROUND: Cancer is the leading cause of death worldwide with breast and prostate cancer the most common among women and men, respectively. Gene expression and image features are independently prognostic of patient survival; but until the advent of spatial transcriptomics (ST), it was not possible to determine how gene expression of cells was tied to their spatial relationships (i.e., topology). METHODS: We identify topology-associated genes (TAGs) that correlate with 700 image topological features (ITFs) in breast and prostate cancer ST samples. Genes and image topological features are independently clustered and correlated with each other. Themes among genes correlated with ITFs are investigated by functional enrichment analysis. RESULTS: Overall, topology-associated genes (TAG) corresponding to extracellular matrix (ECM) and Collagen Type I Trimer gene ontology terms are common to both prostate and breast cancer. In breast cancer specifically, we identify the ZAG-PIP Complex as a TAG. In prostate cancer, we identify distinct TAGs that are enriched for GI dysmotility and the IgA immunoglobulin complex. We identified TAGs in every ST slide regardless of cancer type. CONCLUSIONS: These TAGs are enriched for ontology terms, illustrating the biological relevance to our image topology features and their potential utility in diagnostic and prognostic models.

Facile Synthesis of a Long Afterglow Calcium-Organic Framework in Water.

Presented here is a water-stable Ca-MOF that has been facilely synthesized from the metastable 3D framework in water and exhibits room-temperature phosphorescence with second scale long afterglow.

Patterns of Sexually Transmitted Co-infections and Associated Factors Among Men Who Have Sex With Men: A Cross-Sectional Study in Shenyang, China.

Background: Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infections (STIs). We sought to describe patterns of sexually transmitted co-infections and explore factors associated with increased acquisition of STIs among MSM. Methods: We enrolled MSM in Shenyang, China, between July and December 2020 to test for four STIs, including human papillomavirus (HPV), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Treponema pallidum (TP). Data regarding demographic and behavioral characteristics of participants were collected through a self-administered digital questionnaire. We adopted the ordinal logistic regression model to identify factors associated with acquiring more STIs. Results: Overall, 177 participants with completed test results for all four STIs were analyzed. These participants had a median age of 29.0 (interquartile range: 23.0-38.0) years. The prevalence of STI co-infections was 23.7% [42/177; 95% confidence interval (CI), 17.8%-30.8%], among which HPV/CT (47.1%) and HPV/CT/NG (50.0%) co-infection were the predominant types among participants with dual and multiple infections, respectively. Participants who had a higher educational background [adjusted odds ratio (aOR), 0.46; 95% CI, 0.24-0.85; P = 0.014] and had a history of STIs (aOR, 2.53; 95% CI, 1.24-5.18; P = 0.011) were positively associated with acquiring more STIs. Conclusions: MSM in Shenyang suffer a substantial burden of sexually transmitted co-infections. An optimized multi-STI integration strategy targeting prevention, surveillance, screening, and treatment is warranted to reduce the prevalence of sexually transmitted co-infections, especially in less-educated MSM.

Atmospheric particulate matter aggravates cns demyelination through involvement of TLR-4/NF-kB signaling and microglial activation.

Atmospheric Particulate Matter (PM) is one of the leading environmental risk factors for the global burden of disease. Increasing epidemiological studies demonstrated that PM plays a significant role in CNS demyelinating disorders; however, there is no direct testimony of this, and yet the molecular mechanism by which the occurrence remains unclear. Using multiple in vivo and in vitro strategies, in the present study we demonstrate that PM exposure aggravates neuroinflammation, myelin injury, and dysfunction of movement coordination ability via boosting microglial pro-inflammatory activities, in both the pathological demyelination and physiological myelinogenesis animal models. Indeed, pharmacological disturbance combined with RNA-seq and ChIP-seq suggests that TLR-4/NF-kB signaling mediated a core network of genes that control PM-triggered microglia pathogenicity. In summary, our study defines a novel atmospheric environmental mechanism that mediates PM-aggravated microglia pathogenic activities, and establishes a systematic approach for the investigation of the effects of environmental exposure in neurologic disorders.

Probiotic Therapy (BIO-THREE) Mitigates Intestinal Microbial Imbalance and Intestinal Damage Caused by Oxaliplatin.

Gastrointestinal mucositis associated with the use of chemotherapeutic drugs can seriously affect the quality of life of patients. In this study, a probiotic mixture, BIO-THREE, was used to alleviate intestinal damage caused by oxaliplatin in mice and human patients. Kunming mice were injected with 15 mg/kg of oxaliplatin twice, and BIO-THREE tablets were administered to mice for 12 days. Patients with gastric cancer undergoing oxaliplatin treatment took BIO-THREE tablets for 2 weeks. The changes in the composition of fecal microbiota both in patients and mice were analyzed using 16S rRNA high-throughput sequencing. In mice, oxaliplatin caused a drop in body weight and produced lesions in the liver and small intestines. Probiotic therapy successfully mitigated the damage caused by oxaliplatin to the intestinal tract, but it was not very effective for the liver damage and weight loss caused by oxaliplatin. The sequencing of the gut microflora indicated that oxaliplatin treatment increased the abundance of Bacteroidetes and decreased the abundance of Prevotella in mice. After taking probiotics, the feces of mice and human patients both had a higher abundance of Plovitella and a lower abundance of Bacteroides. The increase in Bacteroidetes and decrease in Prevotella in the gut community might be associated with oxaliplatin-induced intestinal damage. Probiotics appeared to be beneficial, decreasing intestinal damage by restoring the abundance of Bacteroidetes and Prevotella.

Corrigendum: Combination therapy with fingolimod and neural stem cells promotes functional myelination in vivo through a non-immunomodulatory mechanism.

[This corrects the article DOI: 10.3389/fncel.2019.00014.].

High Human Papillomavirus Vaccine Acceptability and Cost-Effectiveness of the Chinese 2-Valent Vaccine Among Men Who Have Sex With Men: A Cross-Sectional Study in Shenyang, China.

Background: Despite the insupportable burden caused by the human papillomavirus (HPV) and high vaccine acceptability, vaccination programs are not currently available for men who have sex with men (MSM). We aimed to assess HPV infection by examining the willingness for vaccination among MSM and cost-effectiveness of the Chinese 2-valent HPV vaccine. Methods: We recruited MSM in Shenyang, China between July and December 2020 to conduct anal HPV testing and an online survey regarding HPV-related knowledge and vaccine acceptability. We performed a cost-effectiveness analysis to evaluate the incremental cost-effectiveness ratios (ICERs) of the Chinese 2-valent HPV vaccine. Results: A total of 234 participants completed the online survey; of those, 203 were successfully tested for HPV. The median age was 30 years [interquartile range (IQR): 23-38 years]. Most participants had at least undergraduate education (136/234, 58.1%). The acceptability rate for the free HPV vaccine was 57.7% (135/234). The prevalence of HPV types 16 and 18 was 14.9% (18/121) and 26.8% (22/82) in the willing and unwilling to vaccinate groups, respectively (P > 0.05). The prevalence of high-risk HPV among participants aged <30 and ≥50 years was 48.6 and 38.9%, respectively. Using the Chinese per capita gross domestic product (GDP) as a threshold, the Chinese 2-valent HPV vaccine would be a "very cost-effective" strategy, with an ICER value of USD 4,411. This evidence showed that the Chinese 2-valent HPV vaccine was more cost-effective than other imported vaccines. Conclusions: Targeted strategies should be utilized in MSM with different rates of vaccine acceptability. A pilot HPV vaccination program based on the Chinese 2-valent HPV vaccine for MSM is urgently warranted to reduce the burden of HPV and anal cancer.

Limosilactobacillus fermentum JL-3 isolated from "Jiangshui" ameliorates hyperuricemia by degrading uric acid.

Recent studies into the beneficial effects of fermented foods have shown that this class of foods are effective in managing hyperuricemia and gout. In this study, the uric acid (UA) degradation ability of Limosilactobacillus fermentum JL-3 strain, isolated from "Jiangshui" (a fermented Chinese food), was investigated. In vitro results showed that JL-3 strain exhibited high degradation capacity and selectivity toward UA. After oral administration to mice for 15 days, JL-3 colonization was continuously detected in the feces of mice. The UA level in urine of mice fed with JL-3 was similar with the control group mice. And the serum UA level of the former was significantly lower (31.3%) than in the control, further confirmed the UA-lowering effect of JL-3 strain. Limosilactobacillus fermentum JL-3 strain also restored some of the inflammatory markers and oxidative stress indicators (IL-1ß, MDA, CRE, blood urea nitrogen) related to hyperuricemia, while the gut microbial diversity results showed that JL-3 could regulate gut microbiota dysbiosis caused by hyperuricemia. Therefore, the probiotic Limosilactobacillus fermentum JL-3 strain is effective in lowering UA levels in mice and could be used as a therapeutic adjunct agent in treating hyperuricemia.

Montelukast alleviates inflammation in experimental autoimmune encephalomyelitis by altering Th17 differentiation in a mouse model.

Montelukast is a leukotriene receptor antagonist that is known to prevent allergic rhinitis and asthma. Blocking the Cysteinyl leukotriene receptor (CysLTR1), one of the primary receptors of leukotrienes, has been demonstrated to be efficacious in ameliorating experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through disrupting chemotaxis of infiltrating T cells. However, the role of CysLTR1 in the pathogenesis of MS is not well understood. Here, we show that MS patients had higher expression of CysLTR1 in the circulation and central nervous system (CNS). The majority of CD4+ T cells expressed CysLTR1 in MS lesions. Among T-cell subsets, Th17 cells had the highest expression of CysLTR1, and blocking CysLTR1 signalling abrogated their development in vitro. Inhibition of CysLTR1 by montelukast suppressed EAE development in both a prophylactic and therapeutic manner and inhibited myelin loss in EAE mice. Similarly, the in vivo results showed that montelukast inhibited Th17 response in EAE mice and that Th17 cells treated with montelukast had reduced encephalitogenic in adoptive EAE. Our findings strongly suggest that targeting Th17 response by inhibiting CysLTR1 signalling could be a promising therapeutic strategy for the treatment of MS and CNS inflammatory diseases.

Fabrication of High χ-Low N Block Copolymers with Thermally Stable Sub-5 nm Microdomains Using Polyzwitterion as a Constituent Block.

In this work, we used zwitterionic poly(4-vinylpyridine) propane-1-sulfonate (PVPS) as a constituent block to construct high χ-low N block copolymers (BCPs) with different neutral polymers as the other block, including polystyrene (PS), poly(ethylene oxide) (PEO), and poly(l-lactide) (PLLA). Lamellar structures with sub-5 nm microdomains were observed in all three types of BCPs. Due to the tendency of self-aggregation induced by electrostatic interaction in polyzwitterion, the Flory-Huggins parameters (χ) between PVPS and most neutral polymers are relatively high, which provides a facile and efficient way to fabricate high χ-low N BCPs. In addition, the dimension of the sub-5 nm structures formed in PVPS-containing BCPs showed high thermal stability with a small fluctuation (±0.1 nm) of domain spacings upon heating.

Neural network-based fault detection for nonlinear networked systems with uncertain medium access constraint: Application to motor systems.

The fault detection for a class of continuous-time nonlinear networked control systems with medium access constraint is concerned in this paper, where the occurring probability of transition from one sensor to another is allowed to be partially unknown and uncertain. First of all, a Markovian system approach is adopted to describe the access process of sensors, in which only one sensor is allowed to access the communication channel. A robust filter based residual generator is proposed to generate the residual signal such that it can be used to indicate whether the fault has occurred or not. The nonlinear term is approximated by a neural network, and the Lyapunov-Krasovskii functional is introduced to analyze the fault detection system, three sufficient conditions for the stochastic stability of fault detection error system are given, and the fault detection filter gains are calculated via solving some matrix inequalities. In the simulation, a second-order DC motor system is used to validate of the main results, which shows the effectiveness of the fault detector design.

Tibet plateau probiotic mitigates chromate toxicity in mice by alleviating oxidative stress in gut microbiota.

Heavy metal contamination in food endangers human health. Probiotics can protect animals and human against heavy metals, but the detoxification mechanism has not been fully clarified. Here, mice were supplemented with Pediococcus acidilactici strain BT36 isolated from Tibetan plateau yogurt, with strong antioxidant activity but no chromate reduction ability for 20 days to ensure gut colonization. Strain BT36 decreased chromate accumulation, reduced oxidative stress, and attenuated histological damage in the liver of mice. 16S rRNA and metatranscriptome sequencing analysis of fecal microbiota showed that BT36 reversed Cr(VI)-induced changes in gut microbial composition and metabolic activity. Specifically, BT36 recovered the expressions of 788 genes, including 34 inherent Cr remediation-relevant genes. Functional analysis of 10 unannotated genes regulated by BT36 suggested the existence of a new Cr(VI)-reduction gene in the gut microbiota. Thus, BT36 can modulate the gut microbiota in response to Cr(VI) induced oxidative stress and protect against Cr toxicity.

Probing exosome internalization pathways through confocal microscopy imaging.

We developed a novel fluorescence labelling method to track exosome internalization pathways in cells by confocal microscopy. The proposed method allows evaluation and comparison of the uptake pathways of exosomes originating from different cells, which would offer the potential for understanding the functions of exosomes in intercellular communication and their applications in drug delivery.

Corrigendum: Scopoletin Suppresses Activation of Dendritic Cells and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling.

[This corrects the article DOI: 10.3389/fphar.2019.00863.].