Enhanced Potentiometric Hydrogen Sensing Response Based on the Ba0.5Sr0.5Co1-yFeyO3-δ Electrode with Unusual Polarity.

In this work, unusual potentiometric hydrogen sensing of mixed conducting Ba0.5Sr0.5Co0.8Fe0.2O3-δ was reported. Inspired by the unusual polarity, a dual sensing electrode (SE) potentiometric hydrogen sensor was fabricated by pairing Ba0.5Sr0.5Co0.8Fe0.2O3-δ with electronic conducting ZnO to enhance the hydrogen response. Hydrogen sensing measurements suggested that significantly higher response, larger sensitivity, and lower limit of detection (LOD) were achieved by the dual SE sensor when compared with the single SE sensor based on Ba0.5Sr0.5Co0.8Fe0.2O3-δ or ZnO. A high response of 97.3 mV for 500 ppm hydrogen and a low LOD of 2.5 ppm were obtained by the dual SE sensor at 450 °C. Furthermore, the effect of the Fe doping concentration in Ba0.5Sr0.5Co1-yFeyO3-δ (y = 0.2, 0.5, and 0.8) on hydrogen sensing response was investigated. The potentiometric response values to hydrogen increased monotonically with increasing Fe doping concentration. With the Fe/Co atomic ratio increased from 0.25 to 4, the responses to 500 ppm hydrogen raised by 69.6 and 94% at 350 and 450 °C, respectively. The sensing behaviors of unusual Ba0.5Sr0.5Co1-yFeyO3-δ may be ascribed to the predominant surface electrostatic effect. These results show that mixed conducting Ba0.5Sr0.5Co1-yFeyO3-δ is desirable for developing high-performance dual SE hydrogen sensors.

SPM4GAC: SPM based approach for genome analysis and classification of macromolecules.

Genome sequence analysis and classification play critical roles in properly understanding an organism's main characteristics, functionalities, and changing (evolving) nature. However, the rapid expansion of genomic data makes genome sequence analysis and classification a challenging task due to the high computational requirements, proper management, and understanding of genomic data. Recently proposed models yielded promising results for the task of genome sequence classification. Nevertheless, these models often ignore the sequential nature of nucleotides, which is crucial for revealing their underlying structure and function. To address this limitation, we present SPM4GAC, a sequential pattern mining (SPM)-based framework to analyze and classify the macromolecule genome sequences of viruses. First, a large dataset containing the genome sequences of various RNA viruses is developed and transformed into a suitable format. On the transformed dataset, algorithms for SPM are used to identify frequent sequential patterns of nucleotide bases. The obtained frequent sequential patterns of bases are then used as features to classify different viruses. Ten classifiers are employed, and their performance is assessed by using several evaluation measures. Finally, a performance comparison of SPM4GAC with state-of-the-art methods for genome sequence classification/detection reveals that SPM4GAC performs better than those methods.

A rapid and high-throughput multiplex genetic detection assay for detection, semi-quantification and virulence genotyping of Helicobacter pylori in non-invasive oral samples.

Aim: This study established a high-throughput multiplex genetic detection assay (HMGA) for rapid identification, semi-quantification and virulence analysis of Helicobacter pylori directly from the clinical non-invasive oral samples. Methods: The gastric mucosa and oral samples were collected from 242 patients in Shanghai from 2021 to 2022. All the samples were detected by routine clinical tests for H. pylori and Sanger sequenced for inconsistent results. A new multiplex PCR assay providing results within 4 hours was designed and optimized involving fluorescent dye-labeled specific primers targeted 16S rRNA gene, semi-quantitative gene ureC and 10 virulence genes of H. pylori. Semi-quantification was carried out by simulating the serial 10-fold dilutions of positive oral samples, and the H. pylori loads in different clinical samples were further compared. The mixed plasmids of virulence genes vacA s1, vacA m1 and vacA m2 were used to evaluate the performance on different genotypes. The consistency of 10 virulence genes in gastric mucosa, saliva, mouthwash and dental plaque of H. pylori-positive patients was compared. Results: The non-invasive HMGA was highly specific for detection of all 12 targets of H. pylori and human internal reference gene ß-globin, and the sensitivity to all target genes could reach 10 copies/µL. Compared with routine clinical tests and sequencing, non-invasive HMGA has a high level (>0.98) of sensitivity, specificity, accuracy, PPV, NPV and kappa coefficient for direct detection of H. pylori in oral samples. Moreover, by detecting peak area levels of ureC, it was confirmed that the H. pylori loads in gastric mucosa were significantly higher than those of the three kinds of oral samples (p<0.05). We also found that 45.0% (91/202) of patients had different H. pylori virulence genes in different oral samples. The concordance of positive detection rates of each virulence gene between saliva and gastric mucosa was more than 78% (p<0.05). Conclusion: The non-invasive HMGA proved to be a reliable method for the rapid H. pylori identification, semi-quantification and detection of 10 virulence genes directly in oral samples, providing a new idea for non-invasive detection of H. pylori.

Network pharmacology-based mechanism prediction and pharmacological validation of Bushenhuoxue formula attenuating postmenopausal osteoporosis in ovariectomized mice.

BACKGROUND: Bushenhuoxue (BSHX) formula, a ten-compound herbal decoction, is widely used to treat postmenopausal osteoporosis (PMOP) in China. However, the mechanism is not clear yet. METHODS: The underlying biological processes and signaling pathways were predicted by network pharmacology. In vivo experimental study, 24 female C57BL/6 J mice were randomly divided into sham, ovariectomized (OVX) and BSHX formula groups. Mice in the latter two groups were subjected to bilateral ovariectomy, and mice in the BSHX formula group were extra treated by BSHX formula at an oral dosage of 0.2 mL/10 g for 8 weeks. The femur samples were harvested for tissue analyses including µCT assay, histology and immunohistochemical (IHC) staining of VEGF signaling. RESULTS: A total of 218 active ingredients and 274 related targets were identified in BSHX formula. After matching with 292 targets of PMOP, 64 overlapping genes were obtained. GO and KEGG enrichment analyses on these 64 genes revealed that angiogenesis and VEGF signaling were considered as the potential therapeutic mechanism of BSHX formula against PMOP. Animal experiments showed that mice in the BSHX formula-treated group presented increased bone mass, microstructural parameters, blood vessel numbers and an activation of VEGF signaling (VEGF, COX2, eNOS and CD31) compared to the OVX mice. CONCLUSION: This study revealed that BSHX formula exerts anti-PMOP effects possibly through activating VEGF signaling-mediated angiogenesis.

Efficacy and safety of IL-23 inhibitors in the treatment of psoriatic arthritis: a meta-analysis based on randomized controlled trials.

In recent years, the use of interleukin (IL) 23 inhibitors in the treatment of psoriatic arthritis (PsA) has been the subject of much research. By specifically binding to the p19 subunit of IL-23, IL-23 inhibitors block downstream signaling pathways and inhibit inflammatory responses. The objective of this study was to assess the clinical efficacy and safety of IL-23 inhibitors in the treatment of PsA. PubMed, Web of Science, Cochrane Library, and EMBASE databases were searched from the time of conception to June 2022 for randomized controlled trials (RCTs) investigating the use of IL-23 in PsA therapy. The main outcome of interest was the American College of Rheumatology 20 (ACR20) response rate at week 24. We included six RCTs (3 studies on guselkumab, 2 on risankizumab, and 1 on tildrakizumab) with a total of 2971 PsA patients in our meta-analysis. We found that the IL-23 inhibitor group showed a significantly higher ACR20 response rate compared to the placebo group (relative risk = 1.74, 95% confidence interval: 1.57-1.92; P < 0.001; I2 = 40%). There was no statistical difference in the risk of adverse events (P = 0.07) and serious adverse events (P = 0.20) between the IL-23 inhibitor and placebo groups. Notably, the rate of elevated transaminases in the IL-23 inhibitor group was higher than the placebo group (relative risk = 1.69; 95%CI 1.29-2.23; P < 0.001; I2 = 24%). In the treatment of PsA, IL-23 inhibitors significantly outperform placebo intervention while maintaining a favorable safety profile.

Injectable Nanomedicine-Hydrogel for NIR Light Photothermal-Chemo Combination Therapy of Tumor.

Traditional hydrogels have drawbacks such as surgical implantation, large wound surfaces, and uncontrollable drug release during tumor treatment. In this paper, targeted nanomedicine has been combined with injectable hydrogel for photothermal-chemotherapy combination therapy. First, targeted nanomedicine (ICG-MTX) was fabricated by combining near-infrared (NIR) photothermal reagents (ICG) and chemotherapy drugs (MTX). The ICG-MTX was then mixed with the hydrogel precursor and radical initiator to obtain an injectable hydrogel precursor solution. Under the irradiation of NIR light, the precursor solution could release alkyl radicals, which promote the transition of the precursor solution from a liquid to a colloidal state. As a result, the nanomedicine could effectively remain at the site of the tumor and continue to be released from the hydrogel. Due to the targeted nature of MTX, the released ICG-MTX could target tumor cells and improve the accuracy of photothermal-chemo combination therapy. The results indicated that the injectable nanomedicine-hydrogel system has a favorable therapeutic effect on tumors.

Rapid and precise identification of bloodstream infections using a pre-treatment protocol combined with high-throughput multiplex genetic detection system.

BACKGROUND: Bloodstream infection (BSI) is a life-threatening condition with high morbidity and mortality rates worldwide. Early diagnosis of BSI is critical to avoid the unnecessary application of antimicrobial agents and for proper treatment. However, the current standard methods based on blood culture are time-consuming, thus failing to provide a timely etiological diagnosis of BSI, and common PCR-based detection might be inhibited by matrix components. METHODS: The current study explored an integrated pre-analytical treatment protocol for whole blood samples, wherein pathogens are enriched and purified by incubation and concentration, and inhibitors are inactivated and removed. Further, this study developed and evaluated a novel high-throughput multiplex genetic detection system (HMGS) to detect 24 of the most clinically prevalent BSI pathogens in blood culture samples and pre-treated whole blood samples. The specificity and sensitivity were evaluated using related reference strains and quantified bacterial/fungal suspensions. The clinical utility of BSI-HMGS combined with the pre-analytical treatment protocol was verified using blood cultures and whole blood samples. RESULTS: The combined pre-treatment protocol and BSI-HMGS was highly specific for target pathogens and possessed a low detection limit for clinical whole blood samples. The pre-treatment protocol could deplete the PCR inhibitors effectively. For blood culture samples, the current method showed 100.0% negative percent agreements and > 87.5% positive percent agreements compared to the reference results based on blood culture findings. For whole blood samples, the current method showed 100.0% negative percent agreements and > 80.0% positive percent agreements compared to the reference results for most pathogens. The turnaround time was ≤ 8 h, and all the procedures could be conducted in a general clinical laboratory. CONCLUSION: The BSI-HMGS combined with the pre-treatment protocol was a practical and promising method for early and precise detection of BSIs, especially for areas without access to advanced medical facilities.

Mechanism Analysis of Heavy Oil Viscosity Reduction by Ultrasound and Viscosity Reducers Based on Molecular Dynamics Simulation.

Ultrasound and viscosity reducers are commonly used methods to reduce the viscosity of heavy oil. In order to compare the viscosity reduction effects of ultrasound and viscosity reducers and study their mechanism of interaction on heavy oil, molecular dynamics simulation was carried out in this paper. First, a molecular model of heavy oil composed of asphaltene, resin, aromatic hydrocarbon, and saturated hydrocarbon was established in this work. Through molecular dynamics simulation, the different effects of ultrasound and viscosity reducers on the viscosity reduction rate, hydrogen bond number, hydrogen bond type, and occupation rate were obtained, and the viscosity reduction mechanism of ultrasound and viscosity reducers was analyzed. By calculating the viscosity reduction rate and the number of hydrogen bonds of five oil-soluble viscosity reducers with or without ultrasound, it was found that the types of hydrogen bonds affecting the viscosity reduction effect were different with or without ultrasound or viscosity reducer, and the type and content of viscosity reducer would affect the effect of ultrasonic viscosity reduction. The amplitude, frequency, and temperature of ultrasound were also the factors affecting the effect of viscosity reducers. The simulation results helped to explain the mechanism of jointly reducing the viscosity of heavy oil by ultrasound and viscosity reducers from the microscopic point of view and provided a theoretical basis for the industrial application of ultrasound and viscosity reducers to reduce the viscosity of heavy oil.

Extraction of Uranium in Nitric Media with Novel Asymmetric Tetra-Alkylcarbamide.

The use of tetra-alkylcarbamides as novel ligands: N,N-butyl-N',N'-hexylurea (L1: ABHU), and N,N-butyl-N',N'-pentylurea (L2: ABPU), for the solvent extraction and complexation behaviors of uranium(VI) was synthesized and investigated in this study. The effects of HNO3 and NO3- concentrations in the aqueous phase on the distribution ratio of U(VI) were examined. Under 5 mol/L HNO3 concentration, DU reached 5.02 and 4.94 respectively without third-phase formation. During the extraction, slope measurements and IR spectral analysis revealed that the U(VI) complexes are a form of UO2(NO3)2·2L for both ligands. In addition, thermodynamic studies showed that the uranium extraction reaction was a spontaneous exothermic reaction. The deep structural analysis of the complexes was realized with DFT calculation. The bond length, bond properties, and topology of the complexes were discussed in detail to analyze the extraction behavior. This study enriches the coordination chemistry of U(VI) by tetra-alkylcarbamides, which may offer new clues for the design and synthesis of novel ligands for the separation, enrichment, and recovery of uranium in the nuclear fuel cycle.

Development of C2-Symmetric Chiral Diphosphine Ligands for Highly Enantioselective Hydrogenation Assisted by Ion Pairing.

A new series of C2-symmetrical chiral ferrocene-based diphosphino-ethane ligands termed as f-DPE were developed. Assisted by the ion pairing interaction with the ligand, a wide scope of 2-substituted acrylic acids was hydrogenated to obtain chiral propanoic acids with high yields and enantioselectivities. The well-known anti-inflammatory drugs ibuprofen, naproxen, and flurbiprofen could be synthesized efficiently. In addition, the synthetic utilities of the current method were demonstrated by gram-scale experiments.

Near-infrared-II light excitation thermosensitive liposomes for photoacoustic imaging-guided enhanced photothermal-chemo synergistic tumor therapy.

Despite the great success of photothermal therapy (PTT), it still suffers from many obstacles, such as the limited penetration depth of light, thermoresistance of tumors, and limitations of mono-therapeutic modalities. Herein, second near-infrared (NIR-II, 1064 nm) light excitation thermosensitive liposomes (DG@TLs) were fabricated for photoacoustic imaging (PAI) guided enhanced PTT-chemotherapy. DG@TLs were constructed by encapsulating NIR-II light excitation semiconducting polymers into liposomes composed of phase change materials (PCMs), along with gambogic acid (GA) with chemotherapeutic and heat shock protein inhibition effects. Under 1064 nm laser irradiation, DG@TLs exhibited superior NIR-II PAI and PTT performances with deep tissue penetration while triggering the thermoresponsive release of GA based on the phase transition of PCMs from solid to liquid. The released GA could enhance the NIR-II PTT efficacy by inhibiting the activity of HSP90, reducing the thermoresistance of tumors, exhibiting significant chemotherapeutic effects, and achieving synergistic anti-tumor efficiency. This work provides a new strategy for achieving on-demand drug release and effective theranostics in deep-seated tumor regions.

A New Multiplex Genetic Detection Assay Method for the Rapid Semi-Quantitative Detection of Six Common Curable Sexually Transmitted Pathogens From the Genital Tract.

Background: Sexually transmitted infections (STIs) are some of the most common communicable conditions and exert impact on the health and lives of many hundreds of millions of people across the world every year. Screening high-risk populations and conducting comprehensive detection tests would lead to a significant improvement in preventing the transmission of STIs and help us to provide rapid treatment to those affected. Here, we successfully established and validated a novel high-throughput multiplex gene detection system (HMGS) for the simultaneous and semiquantitative detection of six important curable sexually transmitted pathogens in a single reaction from secretions samples. Method: Fluorescently labeled primers were designed to target specific conserved and single-copy gene fragments of Ureaplasma urealyticum (U. urealyticum), Mycoplasma hominis (M. hominis), Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoeae), Trichomonas vaginalis (T. vaginalis), and Treponema pallidum (T. pallidum). The specificity and sensitivity of the STI-HMGS was validated and optimized using plasmids and quantitative genomic DNA. Next, we validated the performances of the STI-HMGS for clinical application by testing samples of clinical secretions collected from patients who visited the gynecology and urology outpatient clinics of our reproductive medicine center. Results derived from the STI-HMGS were then compared with three approved commercialized kits that used to detect U. urealyticum, C. trachomatis and N. gonorrhoeae, respectively, followed by further validation with Sanger sequencing for all pathogens. Finally, a comprehensive analysis of epidemiology was performed among different subgroups to investigate the association between infection rates and clinically-relevant information. Results: The sensitivity of STI-HMGS for six target genes was 10 copies/µL. Data derived from the detection of 381 clinical secretions demonstrated that the STI-HMGS exhibited high concordance rate compared with approved commercialized kits and almost 100% sensitivity and specificity for the detection of six sexually transmitted pathogens when validated by Sanger sequencing. Semi-quantitative analysis found that STIs caused by N. gonorrhoeae had a significantly higher (P<0.05) pathogen load than the other pathogens. Infections caused by C. trachomatis were significantly more common in younger individuals (P<0.05). We also found that U. urealyticum infections were more likely to happen in females; while the males were more affected by N. gonorrhoeae (P<0.05). Conclusions: STI-HMGS proved to be an efficient method for the semi-quantitative detection of six important curable sexually transmitted pathogens and therefore represents an alternative method for the clinical detection and monitoring of STIs.

Facile in situ fabrication of biomorphic Co2P-Co3O4/rGO/C as an efficient electrocatalyst for the oxygen reduction reaction.

Streptococcus thermophilus, a Gram-positive (G+) bacterium featuring a teichoic acid-rich cell wall, has been employed as both a phosphorus source and template to synthesize a biomorphic Co2P-Co3O4/rGO/C composite as an efficient electrocatalyst for the oxygen reduction reaction (ORR). Different from the conventional method for the synthesis of phosphides, bio-derivative phosphorus vapor was emitted from the inside out, which facilitated the in situ transformation of the chemically adsorbed Co precursor on the bacteria into Co2P-Co3O4 heterogeneous nanoparticles, which featured a Co2P-rich body and Co3O4-rich surface. Besides, reduced graphene oxide (rGO) was also introduced in the synthetic process to keep Co2P-Co3O4 scattered and further promote the electron transport efficiency. All the Co2P-Co3O4 nanoparticles and rGO sheets were supported on the bacteria-derived carbon substrate with submicron-spherical morphology. The as-obtained Co2P-Co3O4/rGO/C composite exhibited excellent electrocatalytic performance for ORR with onset and half-wave potentials of 0.91 and 0.80 V vs. RHE, respectively. Furthermore, its long-term stability and methanol tolerance were better than those of commercial Pt/C. Thus, this work presents a new strategy of using an interior bio-phosphorus source to obtain heterojunction particles featuring a phosphide-rich body and oxide-rich surface, which may provide some insights for the construction of efficient heterogeneous electrocatalysts.

Zinc-catalyzed regioselective C-P coupling of p-quinol ethers with secondary phosphine oxides to afford 2-phosphinylphenols.

The zinc triflate-catalyzed highly regioselective C-P cross coupling reaction of p-quinol ethers with secondary phosphine oxides is reported. The reaction provides a facile alternative method for the synthesis of 2-phosphinylphenols in good to high yields. Mechanistically, zinc triflate may serve as an oxophilic σ-Lewis acid to activate the C-O bond in p-quinol ether first. Then the regioselective attack of the phosphorus nucleophile at the α-carbon position takes place to form the C-P bond and give the product. In addition, α-alkynyl substituted p-quinol ethers also react with secondary phosphine oxides in the same reaction mode to give 6-alkynyl 2-phosphinylphenols in the presence of the zinc catalyst.

Nuclear-localized AtHSPR links abscisic acid-dependent salt tolerance and antioxidant defense in Arabidopsis.

Salt stress from soil or irrigation water limits plant growth. A T-DNA insertion mutant in C24, named athspr (Arabidopsis thaliana heat shock protein-related), showed several phenotypes, including reduced organ size and enhanced sensitivity to environmental cues. The athspr mutant is severely impaired under salinity levels at which wild-type (WT) plants grow normally. AtHSPR encodes a nuclear-localized protein with ATPase activity, and its expression was enhanced by high salinity and abscisic acid (ABA). Overexpression (OE) of AtHSPR significantly enhanced tolerance to salt stress by increasing the activities of the antioxidant system and by maintaining K(+) /Na(+) homeostasis. Quantitative RT-PCR analyses showed that OE of AtHSPR increased the expression of ABA/stress-responsive, salt overly sensitive (SOS)-related and antioxidant-related genes. In addition, ABA content was reduced in athspr plants with or without salt stress, and exogenous ABA restored WT-like salt tolerance to athspr plants. athspr exhibited increased leaf stomatal density and stomatal index, slower ABA-induced stomatal closure and reduced drought tolerance relative to the WT. AtHSPR OE enhanced drought tolerance by reducing leaf water loss and stomatal aperture. Transcript profiling in athspr showed a differential salt-stress response for genes involved in accumulation of reactive oxygen species (ROS), ABA signaling, cell death, stress response and photosynthesis. Taken together, our results suggested that AtHSPR is involved in salt tolerance in Arabidopsis through modulation of ROS levels, ABA-dependent stomatal closure, photosynthesis and K(+) /Na(+) homeostasis.