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• A single-dose priming vaccination with the bivalent adenovirus-vectored vaccine (Ad5-nCoV/O) induced strong antibody and cellular responses against both the wild type and Omicron variants of SARS-CoV-2. • Both intramuscular and intranasal booster vaccinations using the bivalent Ad5-nCoV/O vaccine resulted in significant serum neutralizing antibody responses. • An intranasal booster, utilizing one-fifth doses of the bivalent Ad5-nCoV/O vaccine after priming with INA, elicited similar levels of neutralizing antibody titers as the intramuscular booster. • Heterologous prime-boost vaccination with Ad5-vectored vaccines after the inactivated vaccine (INA) prime demonstrated higher neutralizing antibody responses compared to homologous prime-boost with INA and INA. The emergence and rapid spread of new mutant strains of SARS-CoV-2 necessitate the development of a new generation vaccine capable of neutralizing a broad range of variants. When the SARS-CoV-2 Omicron variant emerged, individuals in China had already received an inactivated (INA) or a type 5 adenovirus-vectored (Ad5) SARS-CoV-2 vaccine targeting the wild-type virus. We have recently developed a bivalent recombinant type 5 vaccine targeting both the wild-type strain and the Omicron variant (Ad5-nCoV/O). The objectives of this study were to assess the immunogenicity of the bivalent vaccine as a booster against both the wild type and the Omicron variant. In the single immunization model, mice received one intramuscular immunization with monovalent or bivalent Ad5-vectored vaccines targeting both wild-type SARS-CoV-2 and Omicron variants. In the prime-boost model, mice were primed intramuscularly with an INA or Ad5-vectored vaccine targeting wild-type SARS-CoV-2, and then boosted intramuscularly or intranasally with heterologous or homologous INA or monovalent or bivalent Ad5-vectored vaccines targeting both wild-type SARS-CoV-2 and Omicron variants. The vaccine-induced antibody responses and cellular immune responses were measured using ELISA, pseudovirus-based neutralization assays, the intracellular cytokine staining (ICS) and ELISpot. Single-dose prime vaccination with the monovalent and bivalent vaccines elicited robust antibody responses and CD4 + and CD8 + cellular responses against the spike protein of WT and Omicron SARS-CoV-2. Both intramuscular and intranasal boost vaccination with the bivalent Ad5-nCoV/O following a prime with INA or Ad5-vectored vaccines induced strong serum neutralization antibody responses to both wild type and Omicron variants. A heterologous prime-boost vaccination elicited greater neutralization antibody responses than a homologous prime-boost vaccination when mice were boosted with Ad5-vectored vaccines following a prime with INA. Intranasal boost also resulted in significant mucosal IgA responses. The bivalent vaccine Ad5-nCoV/O exhibited robust immunogenicity, inducing broad-spectrum cross-neutralizing antibodies and cellular immune responses against both wild type and Omicron variants of SARS-CoV-2. The results demonstrated the potential of the bivalent vaccine in addressing the challenges posed by emerging SARS-CoV-2 Omicron variants. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is initiated and sustained by self-renewing leukemia stem cells (LSCs). Our recent work using AML models driven by AML-ETO9a and MLL-AF9 revealed that LSCs depend on CD99-mediated protein synthesis regulation. However, it remains unclear if LSCs from specific AML genetic subtypes exhibit distinct dependencies. In the TCGA AML cohort, CD99 was notably elevated in FLT3-ITD but not NRAS-mutated AML. To investigate if LSCs driven by FLT3-ITD or NRAS mutations differ in their dependence on CD99, we generated Cd99-/-;Mx1-Cre;Tet2fl/fl;Flt3ITD/+ (CD99 KO TET2/FLT3) and Cd99-/-;Mx1-Cre;Tet2fl/fl;NrasLSL-G12D/+ mice (CD99 KO TET2/NRAS) mice. TET2 was chosen as a cooperating allele given its frequent co-occurence with FLT3 and NRAS mutations. CD99 deletion in TET2/FLT3 leukemias reduced aberrant donor-derived Mac-1+c-kit+ cells in the peripheral blood and LSCs (LSK CD48+CD150-) in the bone marrow, also attenuating leukocytosis and thrombocytopenia. In contrast, there was no significant impact of CD99 loss in the TET2/NRAS model. In secondary transplants, CD99 loss led to decreased LSC function in the TET2/FLT3 but not the TET2/NRAS model. In vivo O-propargyl-puromycin assays showed that loss of CD99 resulted in increased protein synthesis in TET2/FLT3, but not TET2/NRAS LSCs. In sum, our data demonstrate a dependency on CD99-mediated protein synthesis regulation in FLT3-ITD-, but not NRAS-mutated AML. Given recent studies showing that AMLs harboring FLT3-ITD mutations exhibit more primitive cellular hierarchies as compared to those with NRAS mutations, and that this is associated with higher clinical risk, our results suggest a potential general association between higher-risk AML and dependence on regulated protein synthesis. Such AMLs may be particularly sensitive to therapeutic strategies disrupting regulated protein synthesis. [ABSTRACT FROM AUTHOR]

Introduction: Although treatment approaches to younger fit patients with mantle cell lymphoma (MCL) are well-described, the optimal treatment of older or less fit patients with varying comorbidities is less clear. The objectives of this study were to examine first-line treatment patterns, and the impact of comorbidities and age on treatment choices and overall survival (OS) in a large, predominantly older, Medicare population. Patients and Methods: In Medicare data from 1/1/2007-8/31/2015, 3,008 patients with MCL were identified. Data on age, gender, race, Charlson comorbidities, Charlson comorbidity index (CCI), timing of injectable MCL therapies, and OS were collected and analyzed. Results: Median age of the study population was 75.5 (range, 33–107; 25th, 75th: 69.9, 81.5) years. Over half of the individuals had ≥two comorbidities. The CCI was 1–2 in 45%, and 3–4 in 26.6% of patients. Rituximab was the most commonly used agent, regardless of age or comorbidity, in the first 60 days following diagnosis, being administered to 40.2% of patients. In contrast, administration of cyclophosphamide, doxorubicin, vincristine, or bendamustine in the first 60 days after diagnosis was less common (17.9%, 13.1%, 17.2%, and 12%, respectively). Overall survival was 3.23 (range, 0.003–7.668) years, and decreased with increasing number of comorbidities. Discussion: Our analysis of a real-world patient population with MCL found that older patients have a high rate of comorbidities which impact administered treatment and subsequent OS. Our findings can be used to prospectively guide treatment decisions in these older, frailer, non-transplant-eligible patients, considering the impact of age and comorbidities on such choices. [ABSTRACT FROM AUTHOR]

• The effect of bending deformation on the corrosion behavior is discussed from the microstructure evolution and stress distribution. • Bending deformation causes stress concentration on both sides of the cross-sectional samples. • Discontinuous Si particles in non-brazed samples are unfavorable to the development of intergranular corrosion. • Si "needles" in brazed samples provide effective propagation path for intergranular corrosion. This study provides an insight into the effect of bending deformation on the corrosion behavior of non-brazed and brazed AA4343/AA4047/AA3003/AA4047/AA4343 composite sheet from the rolling direction (RD) and the transverse direction (TD) cross sections, by combining electrochemical measurements, scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD) techniques. Grain size had a greater effect on the corrosion resistance, as compared with the textures. Localized corrosion initiated from intermetallic particles (IMPs) for both non-brazed and brazed samples whether bending or not. After bending deformation, stress concentrations at the outer layer were found in non-brazed and brazed samples. For non-brazed samples, bending deformation had little effect on the corrosion behavior due to the absence of intergranular corrosion (IGC). For brazed samples, Si "needles" provided effective corrosion propagation path, leading to a reduction of corrosion resistance. [Display omitted] [ABSTRACT FROM AUTHOR]

Near-infrared (NIR) light possesses many suitable optophysical properties for medical imaging including low autofluorescence, deep tissue penetration, and minimal light scattering, which together allow for high-resolution imaging of biological tissue. NIR imaging has proven to be a noninvasive and effective real-time imaging methodology that provides a high signal-to-background ratio compared to other potential optical imaging modalities. In response to this, the use of NIR imaging has been extensively explored in the field of immunotherapy. To date, NIR fluorescence imaging has successfully offered reliable monitoring of the localization, dynamics, and function of immune responses, which are vital in assessing not only the efficacy but also the safety of treatments to design immunotherapies optimally. This review aims to provide an overview of the current research on NIR imaging of the immune response. We expect that the use of NIR imaging will expand further in response to the recent success in cancer immunotherapy. We will also offer our insights on how this technology will meet rapidly growing expectations in the future. Unlabelled Image [ABSTRACT FROM AUTHOR]

Benzene homologues are important chemical precursors to the formation of ground-level ozone and secondary organic aerosol (SOA) in the atmosphere, in addition, some toxic species are harmful to human health. Strict countermeasures have been taken to fight air pollution since 2013, and total amount control of volatile organic compounds is being promoted in China at present. Therefore, it is important to understand the pollution situation and the control status of ambient benzene homologues in China. This paper reviews research progress from published papers on pollution characteristics, atmospheric photochemical reactivity, health risk assessment and source identification of ambient benzene homologues in recent years in China, and also summarizes policies and countermeasures for the control of ambient benzene homologues and the relevant achievements. The total ambient levels of benzene, toluene, ethylbenzene and xylenes (BTEX) shows a declining tendency from 2001 to 2016 in China. The mass concentrations of BTEX are generally higher in southern regions than in northern regions, and they present vertical decreasing variation characteristics with increasing altitude within the height range of about 5500 m. Toluene has the highest ozone formation potential and SOA formation potential both in urban areas and background areas, while benzene poses an obvious carcinogenic risk to the exposed adult populations in urban areas. Source identification of ambient benzene homologues suggested that local governments should adopt differentiated control strategies for ambient benzene homologues. Several recommendations are put forward for future research and policy-making on the control of ambient benzene homologues in China. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common joint disease characterized by cartilage degradation. Chondroitin sulfate from shark (CS-S) has a good effect on OA in clinical, but due to source limited of CS from shark. Therefore, it is important to find a novel CS source with similar efficacy to CS-S in the treatment of OA. Herein, we reported a therapeutic effect of CS from scophthalmus maximus (CS-SM) for treating OA in rats. The OA model was established. After intervention with CS-SM by intragastric administration. Our results showed that CS-SM could protect articular cartilage in OA, inhibit the degradation of cartilage, decrease the apoptosis of chondrocytes, decline the content of interleukin-1, tumor necrosis factor-α and Prostaglandins E 2 in synovial fluid, down-regulate the protein expression of matrix metalloproteinase-1 and up-regulate the protein expression of tissue inhibitor of metalloproteinase-1. Our results suggest that oral CS from SM is a new potential therapy for OA. [ABSTRACT FROM AUTHOR]

Localized corrosion of the aluminium alloy AA5083-H111 in a simulated dynamic seawater/air interfacial zone and a full seawater immersion zone was investigated with electrochemical impedance spectroscopy and electrochemical noise. Al-Fe/Ti intermetallic particles (IMPs) on localized corrosion were examined with focused ion beam, transmission electron microscopy and energy dispersive x-ray spectroscopy. As compared with the full immersion zone, the interfacial zone showed higher oxide film resistance and charge transfer resistance, which was attributed to the high oxygen flux in that zone. Localized corrosion arose from IMPs that posessed an Al-Fe phase and a Ti enriched phase. [Display omitted] • A device that simulated a dynamic seawater/air interface was constructed. • Oxide film resistance was higher in a dynamic seawater/air interfacial zone than in a full seawater immersion zone. • Almost all localized corrosion was initiated near Al-Fe/Ti intermetallic particles, which acted as a cathode. • Amorphous corrosion products were formed in a trench between the intermetallic particles and the Al matrix. [ABSTRACT FROM AUTHOR]

Previous studies suggested that the 5-hydroxytryptamine receptor 3B (HTR3B) is involved in heroin dependence by modulating dopamine (DA) release in the reward pathway and that the genetic polymorphisms in HTR3B play plausible role in modulating the risk of developing heroin addiction. To identify markers that contribute to the genetic susceptibility to heroin dependence, we examined the potential associations between heroin dependence and 7 single nucleotide polymorphisms (SNPs) of the HTR3B gene using multiplex SNaPshot technology in a Chinese Han population. Participants included 418 heroin-dependent subjects and 422 healthy controls. The results suggested that the genotype distribution of HTR3B rs1176746 and rs1185027 were significantly different between heroin dependent subjects and healthy controls (both p = 0.004). The frequency of the GG of rs1176746 and AA of rs1185027 genotype in heroin-dependent subjects were significantly higher than that of healthy controls, while the GA of rs1176746 and AT of rs1185027 genotype distributions were much lower. Another SNP, rs10789970, showed a nominally significant p -value in the genotype distribution between heroin dependent subjects and controls ( p = 0.022). These findings indicate the important role of HTR3B polymorphisms in heroin dependence among the Chinese Han population and provide valuable information for further genetic and neurobiological investigations of heroin dependence. [ABSTRACT FROM AUTHOR]

Sodium humate (HA-Na) has been topically used as a wound healing and anti-inflammatory agent in folk medicine. In the present study, HA-Na was investigated for cutaneous wound healing in Sprague–Dawley rats. HA-Na solution (1.0%, w / v ) was topically administered to rats undergoing excision wound models. Healing was assessed with a recombinant bovine basic fibroblast growth factor for external use as positive control. Wound healing rates were calculated on Day 3, 6, 9, 14 and 21 after injury, and tissues were also harvested after the same intervals for histological analysis. In addition, tissue hydroxyproline levels were measured. Furthermore, mRNA levels and protein expressions of transforming growth factor- β 1, 2, 3 (TGF- β 1, 2, 3) were determined by RT-PCR and western blot. Protein expression levels of Smad-2, -3, -4 and -7 were also detected by western blot. Our study demonstrates that HA-Na has the capacity to promote wound healing in rats via accelerated wound contraction and increased hydroxyproline content. More importantly, these wound healing effects of HA-Na might be mediated through the TGF- β /Smad signaling pathway. HA-Na may be an effective agent for enhanced wound healing. [ABSTRACT FROM AUTHOR]

Highlights: [•] A facile one-pot hydrothermal method to synthesize ZnS(MAA) QDs. [•] Synthesis and in situ modification of ZnS(MAA) QDs in a single process. [•] Controllable ZnS(MAA) QD size in the range 4–10nm by varying the reaction time. [•] Excellent dispersibility of ZnS(MAA) QDs in water. [•] 50% of the fluorescence signal intensity retained after storage for 6months. [Copyright &y& Elsevier]

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure, but its etiology is poorly understood. Clonal hematopoiesis (CH) has been shown to promote atherosclerosis and heart failure with reduced ejection fraction, but whether and how CH may promote HFpEF is less well understood. We screened for CH in 109 HFpEF patients at UTSW and identified CH in 25% of patients, as compared with 19% of age/gender-matched controls. The most frequent mutation was in TET2 (63%), and notably 42% of patients with TET2-mutated CH harbored two TET2 mutations. In contrast, mutations in DNMT3A, classically the most frequent mutation in age-associated CH, were present at a much lower rate (30%). To test if TET2-mutated CH promotes HFpEF, we used a mouse model in which a high-fat diet and nitric oxide synthase inhibition by L-NAME recapitulate the clinical features of HFpEF (Nature 2019;568:351). We transplanted pIpC-treated bone marrow from Mx1-Cre;Tet2fl/fl mice or Cre-negative Tet2fl/fl control mice into wild-type mice, and six weeks later we induced HFpEF for 12 weeks. Consistent with our clinical observations, we discovered that recipients of Tet2-null hematopoietic cells exhibited significantly worse diastolic dysfunction. This effect was dependent on the NLRP3 inflammasome and was specific to loss of Tet2, while mice transplanted with Dnmt3a-null bone marrow did not manifest a worse HFpEF phenotype. Additionally, bulk and single-cell transcriptomic analyses revealed that HFpEF induction led to an expansion in the heart of Spp1+ macrophages, which exhibit both pro-inflammatory and pro-fibrotic features, which was exacerbated in the setting of CH. In sum, TET2-mutated CH is common in patients with HFpEF and drives disease pathogenesis in an allele-specific manner. These findings establish a rationale for targeting CH to treat or prevent HFpEF. [ABSTRACT FROM AUTHOR]

Plants are known to develop a multi-faceted innate immune system for pathogenic defense. Systemic acquired resistance (SAR) and induced systemic resistance (ISR) are the two main pathways. Many chemical inducers known as plant activators that activate innate immunity to defend against pathogens have been discovered. Currently, the exploitation of new plant activators is mainly done to develop analogs of salicylic acid as SAR-signaling molecules; however, the ISR pathway is hardly investigated for new plant activators. Based on recent studies on 1-methyl pyrazolo [3,4-d]pyrimidine bioactivity and ATP-induced resistance to biotrophic and necrotrophic pathogens, a new lead compound, 1-methyl-4-amino-pyrazolo [3,4-d]pyrimidine, was obtained as a new scaffold of plant activators for possible inducing ISR immunity system. Additionally, fluorine atom plays an important role in the design and development of new pesticides due to the unique physical chemistry effect, a series of pyrazolo [3,4-d]pyrimidine derivatives were designed and synthesized. Several compounds showed good broad-spectrum induced resistance in vivo , but there was no direct antibacterial activity in vitro. Notably, the introduction of fluorine atom at the para-position of the benzene ring greatly enhanced the induction activity of P1d both involved in SAR and ISR pathways, which implied the inducing resistance both in defending pathogens and insects. [Display omitted] • A series of pyrazolo [3,4-d]pyrimidine derivatives were designed and synthesized. • Several compounds showed good in vivo activity but no direct in vitro activity. • A fluorinated derivative P1d induced both PR1 and PDF1.2 gene expression. [ABSTRACT FROM AUTHOR]

Effluent organic matter (EfOM) from municipal wastewater treatment plants (WWTPs) has received increasing attention due to its impacts on natural and engineered aquatic systems. A comprehensive understanding of molecular compositions of EfOM is crucial for controlling its negative effects and effective removal of it. Fourier transform-ion cyclotron resonance mass spectrometry (FTICR MS) is a powerful method to characterize molecular compositions of EfOM. However, application of this powerful technique is very depending on the sample preparation procedures (i.e. solid phase extraction, SPE) for enrichment and desalting. In this study, a systematic comparison of the difference in molecular compositions of the EfOM extracted using eighteen different SPE sorbents (Envicarb, PPL, ENV, HLB, C18, C18OH, C8, PH, CH, WAX, WCX, MAX, MCX, CBA, C2, CN-E, NH2, and SI) was investigated. Molecular characterization using FTICR MS showed that non-polar sorbents (Envicarb, PPL, ENV, HLB, C18, C18OH) and mixed mode sorbents (WAX, WCX, MAX, MCX) prefer to extract more aromatic and unsaturated molecules, while strongly-polar (SI), mid-polar (CBA, NH2), and weakly non-polar (C2, CN-E) sorbents prefer to extract more aliphatic components. In addition, it is found that combining extracts of CBA, ENV, and EnviCarb sorbents might be a practical way to provide a comprehensive information of molecular composition of EfOM. The results reported in this study provide valuable information on molecular compositions of EfOM and the selectivity of EfOM by different SPE sorbents. Image 1 • Molecular compositions of EfOM extracted by 18 different SPE sorbents were compared. • Non-polar and mixed mode sorbents selectively extract more unsaturated molecules. • Strongly-polar and mid-polar sorbents extract more aliphatic molecules. [ABSTRACT FROM AUTHOR]