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Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity. Here, we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-programmed death-1 (anti-PD-1) and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy, and the patient remained disease-free for 69 months. The patient received DC vaccines loaded with multiple forms of tumor antigens, including mRNA-tumor associated antigens (TAA), mRNA-neoantigens, and hypochlorous acid (HOCl)-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex (MHC) class I and II antigen presentation. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy-related adverse events were observed during the treatment. Robust antitumor CD4 + and CD8 + T-cell responses were detected. The patient remains free of disease progression. This is the first case report on the combination of the above three agents to treat glioblastoma patients. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient. A large-scale trial to validate these findings is warranted., Competing Interests: You-Wen He and Shi-You Li are co-founders of Tricision Biotherapeutics Inc., and the contribution of You-Wen He in this project was through his scientific advisor to tricision Biotherapeutic Inc. Sheng-Nan Sun, Jun Jiang, Qian-Ting Wang, and Shi-You Li are full-time employees of Tricision Biotherapeutics Inc. You-Wen He and Jun O. Liu are co-inventors of the TriVac technology patented by Duke University and Johns Hopkins University and co-founders of TriVac Inc. TriVac technology used by Tricision Biotherapeutics Inc. was licensed by Duke/JHU through TriVac Inc. Other authors declare that there are no conflicts of interest., (© 2023 The Author(s).)

Clostridium difficile infection (CDI) in human and animals belonged usually to antibiotic-associated diarrhea, ranging in severity from mild to life-threatening intestinal tract illnesses. This study aimed to isolation and characterization, toxin genes test, molecular typing, and drug sensitivity of Clostridium difficile ( C. difficile ) which were isolated from clinical diseased dogs and cats. A total of 247 clinical samples were collected from five animal hospitals in Lanzhou City of Northwest China, of which dogs and cats accounted for 74.9% (185/247) and 25.1% (62/247), respectively. We successfully identified 24 C. difficile strains by 16S rRNA and Matrix-Assisted Laser Desorption/Ionization Time of Fight Mass Spectroscopy (MALDI-TOF-MS). 10.3% (19/185) of dogs and 8.1% (5/62) of cats were positive for C. difficile . Among them, 16 strains were toxic and 8 were non-toxic, with a toxic rate of 57.9% (11/19) in dogs and 100% (5/5) in cats. A total of 10 STs and 10 RTs were identified in this study. The percentages of ST42 (RT106) and ST2 (RT014/LW01) among 16 toxic strains were 41.7 and 12.5%, respectively. However, ST3 (RT001), ST1 (RT027), ST133 (LW04), and ST-UN (LW04) had only one strain. ST42 (RT106) was the most common genotype and RT027 strain was first isolated in China from pets. Antimicrobial susceptibility test showed that isolates were extremely sensitive to vancomycin and metronidazole but were resistant to erythromycin and ciprofloxacin. The drug resistant rates to clindamycin, levofloxacin, moxifloxacin and meropenem were 62.5, 20.8, 16.7, and 8.3%, respectively. In conclusion, C. difficile was quietly prevalent in dogs and cats in Lanzhou city with RT106 and RT014 as the main ribotypes. The CDI in pets should be paying more attention and further studies are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wen, Li, Qin, Yang, Bai, Ge, Liu and Li.)

The objective of this study was to observe the effects of anthocyanin from purple corn on blood biochemical indexes, ruminal fluid fermentation parameters, and the microbial population in goats. A total of 18 Qianbei Ma wether kids (body weight, 21.38 ± 1.61 kg; mean ± standard deviation) were randomly assigned to three groups using a completely randomized design. The group diets were: (1) control, basal diet, (2) treatment 1 (LA), basal diet with 0.5-g/d purple corn pigment (PCP), and (3) treatment 2 (HA), basal diet with 1-g/d PCP. The results showed that supplementation of PCP anthocyanin increased ( P < 0.05) crude protein and gross energy digestibilities compared to the control. Compared to the control group, the inclusion of anthocyanin-rich PCP led to significantly increased ( P < 0.05) plasma reduced glutathione and peroxidase concentrations. Goats receiving PCP had increased ( P < 0.05) ruminal fluid acetic acid and a higher ratio of acetate to propionate, while the propionic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid levels had decreased ( P < 0.05). There was no significant difference ( P > 0.05) in ruminal fluid alpha bacterial diversity among the three groups. At the phylum level, the feeding of PCP had significant effect ( P < 0.05) on the abundances of Actinobacteriota, Proteobacteria, Elusimicrobiota , WPS-2, and Cyanobacteria . At the genus level, HA group had lower ( P < 0.05) Prevotellaceae &#95;NK3B31&#95;group abundance compared to the other groups. In addition, significant differences ( P < 0.05) were also observed for the ruminal fluid Eubacterium &#95;nodatum&#95;group, Amnipila, Ruminiclostridium , U29-B03, unclassified&#95;c&#95; Clostridia, Pyramidobacter, Anaeroplasma , UCG-004, Atopobium , norank&#95;f&#95;norank&#95;o&#95; Bradymonadales, Elusimicrobium , norank&#95;f&#95;norank&#95;o&#95;norank&#95;c&#95;norank&#95;p&#95;WPS-2, norank&#95;f&#95; Bacteroidales &#95;UCG-001, and norank&#95;f&#95;norank&#95;o&#95; Gastranaerophilales among all groups. Taken together, the inclusion of anthocyanin-rich PCP increased the antioxidant potential, improved rumen volatile fatty acids, and induced a shift in the structure and relative abundance of ruminal microbiota in growing goats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tian, Li, Luo, Zhou, Long, Wang, Lu and Wen.)

To explore alkaline fuel cells in practice, searching low-cost and efficient alternatives to Pt-based catalysts is urgent yet challenging for oxygen reduction reaction (ORR). Herein, Co 3 Fe 7 alloy nanoparticles wrapped in N-doped defect-rich carbon nanosheets (Co 3 Fe 7 /CNs) were synthesized at 800 °C by a one-step pyrolysis of the mixture (dicyandiamide, iron (II) phthalocyanine (FePc), cobalt (II) phthalocyanine (CoPc) and Fe 2 O 3 ), defined as Co 3 Fe 7 /CNs-800 for simplicity. The pyrolysis temperature and the dosages of dicyandiamide closely correlated to the ORR performance of the resultant catalysts in 0.1 M KOH solution. Significantly, the optimized Co 3 Fe 7 /CNs-800 exhibited encouraging onset potential (E onset  = 0.97 V) and half-wave potential (E 1/2  = 0.85 V) in the alkaline media, surpassing commercial Pt/C (50 wt%, E onset  = 0.96 V, E 1/2  = 0.84 V). This work provides a feasible strategy for developing efficient non-noble metal ORR electrocatalysts in the alkaline condition., (Copyright © 2020 Elsevier Inc. All rights reserved.)

There is an urgent need to construct highly selective low-cost sensors for fast detection of toxic metal ions such as cadmium. When compared with 3D bulk materials, 2D layered materials after activation treatments show superior performances for electrochemical metal ion detection. The bulk graphitic carbon nitride (hereafter b-g-C 3 N 4 ) was prepared by thermal polymerization with urea as a precursor; it was then activated through ultrasonic liquid exfoliation and protonation which resulted in successful fabrication of activated ultrathin g-C 3 N 4 nanosheets (hereafter a-g-C 3 N 4 ). The a-g-C 3 N 4 -modified glassy carbon electrode demonstrates excellent electrochemical performances for Cd 2+ detection with 22.668 μA/μM sensitivity and 3.9 nM LOD (S/N = 3) due to high specific surface area and active sites created on the 2D layered structure. The chemical interference of Pb 2+ , Cu 2+ , and Hg 2+ on Cd 2+ detection was minimal. We have also measured Cd 2+ in natural water and rice samples using the newly developed a-g-C 3 N 4 -modified electrode with high spike recoveries. Our results demonstrate the potential applications of newly developed a-g-C 3 N 4 -modified electrode for rapid detection of toxic metal ions in different sample matrixes. Graphical Abstract The activated g-C 3 N 4 nanosheets (a-g-C 3 N 4 ) were synthesized and used to construct electrochemical sensors with high sensitivity and anti-interference performance.

Green and efficient non-precious metal electrocatalysts for oxygen reduction reaction (ORR) are prepared to meet the increasing demand for clean, secure and sustainable energy. Herein, we report a novel and environmentally friendly strategy for synthesis of graphene-wrapped iron carbide (Fe 7 C 3 ) nanoparticles supported on hierarchical fibrous N-doped graphene with open-mesoporous structures (Fe 7 C 3 /NG) by simply annealing the mixture of melamine, iron (II) phthalocyanine (FePc) and Fe 2 O 3 . The effects of the pyrolysis temperature and the molar ratio of FePc to melamine were critically examined in the controls. Remarkably, the Fe 7 C 3 /NG obtained at 800 °C (i.e. Fe 7 C 3 /NG-800) manifested the forward shifts in the onset potential (0.98 V) and half-wave potential (0.85 V) with respective to commercial Pt/C (50 wt%) in 0.1 M KOH, coupled with the great enhancement in the durability (still remained 92.11% of its initial current density even after 40,000 s) and strong methanol tolerance. This research presents a promising strategy for developing Pt-free non-precious efficient ORR electrocatalysts in fuel cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Frequent harmful cyanobacteria blooms limit the sustainable development of aquaculture. Algicidal bacteria can efficiently control harmful algae without secondary pollution. The algicidal bacteria CZBC1 can lyse Oscillatoria spp. and other harmful cyanobacteria, but its effector mechanism and algicidal threshold are unknown. In this study, we examined the algicidal effect of CZBC1 on O. chlorina, O. tenuis, and O. planctonica by microscopic enumeration and scanning electron microscopy observation. Then, we examined the alginolytic effects of CZBC1 (concentrations 10 3 -10 6 colony forming units (cfu)/mL) on these three species (concentrations 10 3 -10 6 cells/mL) to determine the effective concentrations of CZBC1 for Oscillatoria spp. alginolysis. Results showed that CZBC1 can directly lyse O. chlorina and O. tenuis but indirectly lyse O. planctonica. When the initial concentration of CZBC1 was 10 6 cfu/mL, alginolytic effects were high for all three species at all concentrations, and the alginolytic rate could reach 100% in 3-9 days. When the initial concentration of CZBC1 was lower (10 3  cfu/mL), its inhibitory effects were delayed by 2-5 days, but the cell counts were significantly decreased compared with the control, evidencing significant alginolysis. In addition, the higher the concentration of the algicidal bacteria suspension, the more significant the alginolytic effects. Our results indicate that CZBC1 has different alginolytic mechanisms for O. chlorina, O. tenuis, and O. planctonica, and that different initial concentrations of CZBC1 have different alginolytic effects on these algal species.

High activity and good durability of electrocatalysts are of significance in practical applications of fuel cells. Among them, multi-component metallic hollow nanocages/nanoframes show great potential as advanced catalysts because of their highly open structures, large surface area and good stability. Herein, we report a general uric acid-mediated solvothermal method for shape-controlled synthesis of rhombic-like Pt 35 Cu 65 hollow nanocages (HNCs) with uric acid as co-reductant and co-structure-directing agent. Uric acid and cetyltrimethylammonium chloride (CTAC) played important roles in the hollow cages. The specific architectures showed remarkably enhanced catalytic properties towards glycerol oxidation reaction (GOR), ethylene glycol oxidation reaction (EGOR) and oxygen reduction reaction (ORR) with the enhanced specific activity, outperforming commercial Pt/C (20 wt%). This work provides a new avenue for rational design of novel bimetallic nanocatalysts with enhanced characters in energy storage and conversion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

It is a great challenge to develop simple approach to construct three-dimensional (3D) bimetallic alloyed nanoframes (NFs) with tunable surface structures, albeit with the availability of noble metal NFs in catalysis. Herein, a one-pot solvothermal method was employed for scalable preparation of uniform hollow PtCu rhombic dodecahedron nanoframes (PtCu RDNFs) in the presence of cetyltrimethylammonium chloride (CTAC), where diglycolamine (DGA) served as the co-reductant and co-structure director. The above architectures had the larger electrochemically active surface area (ECSA, 36.85 m 2  g -1 Pt ) than that of commercial Pt black (15.85 m 2  g -1 Pt ), along with the improved catalytic characters for hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR) in acid electrolytes alternative to those of Pt black. It demonstrates great potential applications of PtCu RDNFs in fuel cells and beyond., (Copyright © 2018 Elsevier Inc. All rights reserved.)

An in-situ experiment was conducted to investigate the effect of tropical storm on the white spot syndrome virus (WSSV) loads in Litopenaeus vannamei rearing ponds. White spot syndrome virus loads, heterotrophic bacteria, Vibrio and water quality (including temperature, dissolved oxygen (DO), salinity, pH, NH 4 -N, and NO 2 -N) were continually monitored through one tropical storm. The WSSV loads decreased when tropical storm made landfall, and substantially increased when typhoon passed. The variation of WSSV loads was correlated with DO, temperature, heterotrophic bacteria count, and ammonia-N concentrations. These results suggested that maintaining high level DO and promoting heterotrophic bacteria growth in the shrimp ponds might prevent the diseases' outbreak after the landfall of tropical storm.

Objective: To analyze the characteristic of changes in extravascular lung water index (EVLWI) of H7N9 avian influenza patients who complicated with acute respiratory distress syndrome (ARDS), and to approach the relevance between EVLWI and severity, pulmonary oxygenation in patients with lung injury., Methods: Four H7N9 avian influenza patients administered from April to June in 2013 in First Affiliated Hospital of Nanchang University were studied. The patients who suffered from severe ARDS were administered with low tide volume ventilation plus positive end-expiratory pressure (PEEP), namely protected ventilation strategy, with monitoring hemodynamic parameters and EVLWI through pulse-indicated continuous cardiac output (PiCCO) catheter. During ventilation, patients' parameters, such as PEEP, fraction of inspired oxygen (FiO2), arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), cardiac index (CI), systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), EVLWI, and central venous pressure (CVP) were collected., Results: All 4 H7N9 avian influenza patients were complicated with ARDS, 2 patients were classified to severe ARDS and administered with comprehensive therapies, specially protected ventilation strategy; ventilation duration was 9 days and 30 days respectively, and PiCCO monitoring was 9 days and 21 days respectively. EVLWI of 2 patients on the 1st, 2nd, 3rd day was 10.0±3.2 ml/kg, 12.0±2.9 ml/kg, 14.0±4.2 ml/kg, and 24.0±6.7 ml/kg, 24.0±6.1 ml/kg, 23.0±5.8 ml/kg, respectively. As their conditions became better, patients' EVLWI decreased to 5.5±2.7 ml/kg and 7.0±3.0 ml/kg, respectively at weaning. PEEP and FiO2 of 2 patients were down-regulated, PaO2/FiO2 increased to 334±64 mm Hg and 142±53 mm Hg at weaning. However, no significant changes in CI, SVRI, PVRI and CVP in the 2 patients were observed., Conclusions: EVLWI increases when H7N9 avian influenza patients are complicated with severe ARDS. As the conditions get better, EVLWI returns to normal value gradually. There is relevance between the motive changes in EVLWI and severity of ARDS and pulmonary oxygenation.

Gold nanoparticles immobilized on gold surfaces (AuNPs/Au) function as an excellent SERS substrate for the detection of bacteria biomarkers. The possibility of the reactivity of bacteria biomarkers on such a nanoparticle-based substrate poses complications for the spectroscopic identification and quantification. This report describes new findings of an investigation of the SERS characteristics for the competitive adsorption of dipicolinic acid (DPA), which is an important biomarker from bacterial spores, and pyridine (Py), which is a possible decarboxylation product of DPA. The comparison focuses on the diagnostic region of 900-1100 cm(-1) associated with the ring-breathing modes of the two molecules. While the SERS spectra in this region appeared to display some similarities between DPA and Py, distinctive differences in the detailed band characteristics were revealed for both individual and competitive adsorptions on the AuNPs/Au substrates. The fact that the equilibrium constant for the adsorption of Py on the substrate (~8 × 10(5) M(-1)) is larger than that for DPA (~2 × 10(5) M(-1)) in the measured concentration region is attributed to a stronger binding of Py to Au surface than that for DPA. The analysis of the differences has provided not only accurate speciation of the biomarker molecules on the gold nanoparticle based substrates under the SERS measurement conditions, but also has implications for expanding the application of the nanoparticle substrates for highly sensitive and selective detection of bacterial biomarkers under various reactive or non-reactive conditions.

Gamma-tubulin gene is a very important house-keeping gene and plays key roles in cell division, microtubule nucleation and cell cycle regulation in both plants and animals. In this paper, we studied the gamma-tubulin gene silencing in Nicotiana tabacum var. Samsun NN using the recombinant PVX vector with D fragment of gamma-tubulin cDNA. Special phenotype appeared from recombinant PVX-vector-infected plants, the different morphological leaves grew alternatively in leaf layers (Figs.3-5), and all the buds fell off gradually (Fig.4), resulting in failure of all the microspores to develop to the tetrad stage (Fig.8). The silencing initiated from the apical tissue and kept on until it was mature (Figs.3, 4). There was the increasing of target gene mRNA obviously during gene silencing, even to exceed the positive control (Fig.6). The PVX vector was also suppressed strongly and could fluctuate to some degree (Fig.9), which was probably correlated with target gene mRNA expression.

Objective: To investigate the changes in the serum content of immunoreactive calcitonin (iCT) after burns or inhalation injury, and to explore its diagnostic significance., Methods: Twenty-four dogs were randomized into 4 groups, i. e. A (n = 6, with moderate degree inhalation injury) , B ( n = 6, with severe inhalation injury), C (n = 6, with most severe inhalation injury) and D (n = 6, with severe burns) groups. The serum content of iCT and blood gas analysis before and after injury were determined at different time points. The degree of inhalation injury was determined with fibrobronchoscopic examination at 6 post-inhalation injury hour (PIH)., Results: (1) Fiber bronchoscopic examination showed that the degree of inhalation injury in each group was coincident with the anticipation. (2) The serum content of iCT in each group at 1 PIH was obviously higher than that before injury, and it was evidently higher in A, B and C groups than that in D group at 4 PIH. The peak value of iCT in group A at 24 PIH was (453+/-224) ng/L, and it increased gradually in B and C groups at 48 PIH. The serum content of iCT increased continually from 2 PIH on, and it reached (125+/-41) ng/L at 48 PIH. (3) Compared with PaO2 value before injury (109+/-8) mmHg, there was no obvious difference of the PaO, in A and D groups. PaO2 value in B and C group began to descend continually at 8 PIH (65+/-6) mmHg, and that in C group began to descend at 4 PIH (71+/-9) mmHg. PaCO2 value in C group began to increase at 24 PIH(52+/-11) mmHg when compared with that before injury(38+/-5 ) mmHg., Conclusion: The changes in the serum level of iCT within 8 PIH occurred much earlier than PaO2 and PaCO2, thus it has the same diagnostic significance as fibers bronchoscopic examination.

Four optical isomers of the new cholinolytic compound 3-(2-phenyl-2-cyclopentyl-2-hydroxyl-ethoxy)-quinuclidine (I) have been asymmetrically synthesized by two methods. Method one: Recemic 1-phenyl-1-cyclopentylepoxyethane reacting with 3R or 3S-quinuclidinol produces a mixture of (R-1) and (R-2) or (S-1) and (S-2) respectively. The chemical yields varied from 57% to 78%. The highest % de is 22 and the major product is (R-1) or (S-1). Method two: Grignard reaction of 3R or 3S-benzoyl-methoxy-quinuclidine with cyclopentyl magnesium bromide yields a mixture of (R-1) and (R-2) or (S-1) and (S-2). The chemical yield is 80%. The highest % de is 81 and the major product is (R-2) or (S-2). Preliminary evaluation of the four new optical isomers revealed the following series of biological potencies: (R-2) greater than (I) greater than (S-1) greater than (R-1) greater than (S-2). In the coupling of the compounds with the active centers of M receptors, the absolute configurations in carbon-3 of the quinuclidinyl group and carbon-2 of the substituted ethyl group play an important role. The influence of carbon-2R is greater than that of carbon-3R on cholinolytic potency.