Clinical Characteristics and Outcomes of Severe or Critical COVID-19 Patients Presenting No Respiratory Symptoms or Fever at Onset

It is difficult to identify suspected cases of atypical patients with coronavirus disease 2019 (COVID-19), and data on severe or critical patients are scanty. This retrospective study presents the clinical, laboratory, and radiological profiles, treatments, and outcomes of atypical COVID-19 patients without respiratory symptoms or fever at onset. The study examined ten atypical patients out of 909 severe or critical patients diagnosed with COVID-19 in Wuhan Union Hospital West Campus between 25 January 2020 and 10 February 2020. Data were obtained from the electronic medical records of severe or critical patients without respiratory symptoms or fever at onset. Outcomes were followed up to discharge or death. Among 943 COVID-19 patients, 909 (96.4%) were severe or critical type. Of the severe or critical patients, ten (1.1%) presented without respiratory symptoms or fever at admission. The median age of the ten participants was 63 years (interquartile range (IQR): 57–72), and seven participants were men. The median time from symptom onset to admission was 14 d (IQR: 7–20). Eight of the ten patients had chronic diseases. The patients had fatigue (n = 5), headache or dizziness (n = 4), diarrhea (n = 5), anorexia (n = 3), nausea or vomiting (n = 3), and eye discomfort (n = 1). Four patients were found to have lymphopenia. Imaging examination revealed that nine patients had bilateral pneumonia and one had unilateral pneumonia. Eventually, two patients died and eight were discharged. In the discharged patients, the median time from admission to discharge lasted 24 d (IQR: 13–43). In summary, some severe or critical COVID-19 patients were found to have no respiratory symptoms or fever at onset. All such atypical cases should be identified and quarantined as early as possible, since they tend to have a prolonged hospital stay or fatal outcomes. Chest computed tomography (CT) scan and nucleic acid detection should be performed immediately on close contacts of COVID-19 patients to screen out those with atypical infections, even if the contacts present without respiratory symptoms or fever at onset.     

Studies on the electrochemical preparation of MgCeCo alloy thin films on Cu substrates in urea–DMSO system

Cyclic voltammetry was used to investigate the electrochemical behaviors of Mg(II), Ce(III) and Co(II) in 3.00 mol L^− 1 urea–DMSO (dimethylsulfoxide). The electrode processes of Mg(II), Ce(III) and Co(II) reducing on Pt electrodes were irreversible steps. The transfer coefficient of Mg(II), Ce(III) and Co(II) in 3.00 mol L^− 1 urea–DMSO system was calculated as 0.07, 0.05 and 0.05 at 298.15 K, respectively. The diffusion coefficient of Mg(II), Ce(III) and Co(II) in 3.00 mol L^− 1 urea–DMSO system was calculated as 2.27 × 10^− 10, 1.77 × 10^− 10 and 3.16 × 10^− 10 m² s^− 1 at 298.15 K, respectively. The MgCeCo alloy thin films with smooth, uniform and metallic luster were obtained on Cu substrates by cyclic electrodeposition in 0.01 mol L^− 1 Mg(ClO₄)₂–0.01 mol·L^− 1 Ce(CH₃SO₃)₃₋0.01 mol L^− 1 CoCl₂–3.00 mol L^− 1 urea–DMSO system. The potential sweep rate was found to be important with respect to the adhesion of the thin films.     

Putative Mode of Action of the Monoterpenoids Linalool,Methyl Eugenol,Estragole, and Citronellal on Ligand-Gated Ion Channels

Essential oil has been used as sedatives, anticonvulsants, and local anesthetics in traditional medical remedies; as preservatives for food, fruit, vegetable, and grain storage; and as bio-pesticides for food production. Linalool (LL), along with a few other major components such as methyl eugenol (ME), estragole (EG), and citronellal, are the active chemicals in many essential oils such as basil oil. Basil oil and the aforementioned monoterpenoids are potent against insect pests. However, the molecular mechanism of action of these chemical constituents is not well understood. It is well-known that the γ-aminobutyric acid type A receptors (GABA_ARs) and nicotinic acetylcholine receptor (nAChR) are primary molecular targets of the synthetic insecticides used in the market today. Furthermore, the GABA_AR-targeted therapeutics have been used in clinics for many decades, including barbiturates and benzodiazepines, to name just a few. In this research, we studied the electrophysiological effects of LL, ME, EG, and citronellal on GABA_AR and nAChR to further understand their versatility as therapeutic agents in traditional remedies and as insecticides. Our results revealed that LL inhibits both GABA_AR and nAChR, which may explain its insecticidal activity. LL is a concentration-dependent, non-competitive inhibitor on GABA_AR, as the half-maximal effective concentration (EC₅₀) values of γ-aminobutyric acid (GABA) for the rat α1β3γ2L GABA_AR were not affected by LL: (36.2 ± 7.9) μmol·L⁻¹ and (36.1 ± 23.8) μmol·L⁻¹ in the absence and presence of 5 mmol·L⁻¹ LL, respectively. The half-maximal inhibitory concentration (IC₅₀) of LL on GABA_AR was approximately 3.2 mmol·L⁻¹. Considering that multiple monoterpenoids are found within the same essential oil, it is likely that LL has a synergistic effect with ME, which has been previously characterized as both a GABA_AR agonist and a positive allosteric modulator, and with other monoterpenoids, which offers a possible explanation for the sedative and anticonvulsant effects and the insecticidal activities of LL.     

Efficacy and Safety of Triazavirin Therapy for Coronavirus Disease 2019: A Pilot Randomized Controlled Trial

No therapeutics have been proven effective yet for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the efficacy and safety of Triazavirin therapy for COVID-19, we conducted a randomized, double-blinded controlled trial involving hospitalized adult patients with COVID-19. Participants were enrolled from ten sites, and were randomized into two arms of the study with a ratio of 1:1. Patients were treated with Triazavirin 250 mg versus a placebo three or four times a day for 7 d. The primary outcome was set as the time to clinical improvement, defined as normalization of body temperature, respiratory rate, oxygen saturation, cough, and absorption of pulmonary infection by chest computed tomography (CT) until 28 d after randomization. Secondary outcomes included individual components of the primary outcome, the mean time and proportion of inflammatory absorption in the lung, and the conversion rate to a repeated negative SARS-CoV-2 nucleic acid test of throat swab sampling. Concomitant therapeutic treatments, adverse events, and serious adverse events were recorded. Our study was halted after the recruitment of 52 patients, since the number of new infections in the participating hospitals decreased greatly. We randomized 52 patients for treatment with Triazavirin (n = 26) or a placebo (n = 26). We found no differences in the time to clinical improvement (median, 7 d versus 12 d; risk ratio (RR), 2.0; 95% confidence interval (CI), 0.7–5.6; p = 0.2), with clinical improvement occurring in ten patients in the Triazavirin group and six patients in the placebo group (38.5% versus 23.1%; RR, 2.1; 95% CI, 0.6–7.0; p = 0.2). All components of the primary outcome normalized within 28 d, with the exception of absorption of pulmonary infection (Triazavirin 50.0%, placebo 26.1%). Patients in the Triazavirin group used less frequent concomitant therapies for respiratory, cardiac, renal, hepatic, or coagulation supports. Although no statistically significant evidence was found to indicate that Triazavirin benefits COVID-19 patients, our observations indicated possible benefits from its use to treat COVID-19 due to its antiviral effects. Further study is required for confirmation.     

Synthesis,Characterization, and Antifungal Evaluation of Thiolactomycin Derivatives

5-Substituted benzylidene 3-acylthiotetronic acids are antifungal. A series of 3-acylthiotetronic acid derivatives with varying substitutions at the 5-position were designed, synthesized, and characterized, based on the binding pose of 3-acyl thiolactone with the protein C171Q KasA. Fungicidal activities of these compounds were screened against Valsa Mali, Curvularia lunata, Fusarium graminearum, and Fusarium oxysporum f. sp. lycopersici. Most target compounds exhibited excellent fungicidal activities against target fungi at the concentration of 50 μg·mL⁻¹. Compounds 11c and 11i displayed the highest activity with a broad spectrum. The median effective concentration (EC₅₀) values of 11c and 11i were 1.9–10.7 and 3.1–7.8 μg·mL⁻¹, respectively, against the tested fungi, while the EC₅₀ values of the fungicides azoxystrobin, carbendazim, and fluopyram were respectively 0.30, 4.22, and > 50 μg·mL⁻¹ against V. Mali; 6.7, 41.7, and 0.18 μg·mL⁻¹ against C. lunata; 22.4, 0.42, and 0.43 μg·mL⁻¹ against F. graminearum; and 4.3, 0.12, and > 50 μg·mL⁻¹ against F. oxysporum f. sp. lycopersici. The structures and activities of the target compounds against C. lunata were analyzed to obtain a statistically significant comparative molecular field analysis (CoMFA) model with high prediction abilities (q² = 0.9816, r² = 0.8060), and its reliability was verified. The different substituents on the benzylidene at the 5-position had significant effects on the activity, while the introduction of a halogen atom at the benzene ring of benzylidene was able to improve the activity against the tested fungi.     

Effect of Zn addition,strain rate and deformation temperature on the tensile properties of Sn–3.3 wt.% Ag solder alloy

Stress–strain characteristics of the binary Sn–3.3 wt.% Ag and the tertiary Sn–3.3 wt.% Ag–1 wt.% Zn solder alloys were investigated at various strain rates (SR, ε^·) from 2.6 × 10^− 4 to 1.0 × 10^− 2 s^− 1 and deformation temperatures from 300 to 373 K. Addition of 1 wt.% Zn to the binary alloy increased the yield stress σ_y and the ultimate tensile stress σ_UTS while a decrease of ductility (total elongation ε_T) was observed. Increasing the strain rate (ε^·) increased both σ_y and σ_UTS according to the power law σ = C ε^·m. A normal decrease of ε_T with strain rate was observed according to an empirical equation of the form ε_T = A exp (− λε^·); A and λ are constants. Increasing the deformation temperature decreased both σ_y and σ_UTS in both alloys, and decreased the total elongation ε_T in the Zn-free binary alloy, whereas ε_T was increased in the Zn-containing alloy. The activation energy was determined as 41 and 20 kJ mol^− 1 for these alloys, respectively. The results obtained were interpreted in terms of the variation of the internal microstructure in both alloys. The internal microstructural variations in the present study were evaluated by optical microscopy, electron microscopy and X-ray diffraction. The results show the importance of Zn addition in enhancing the mechanical strength of the Sn–3.3 wt.% Ag base alloy.     

Temporal Profiles of Antibody Responses,Cytokines, and Survival of COVID-19 Patients: A Retrospective Cohort

The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the associations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization. The seropositive rates of IgG and IgM were 29.6% and 48.1%, respectively, in the first week, and plateaued within five weeks. For the patients discharged from the hospital, the IgM decreased slowly, while high levels of IgG were maintained at around 188 AU·mL⁻¹ for the 12 weeks since illness onset. In contrast, in the patients who subsequently died, IgM declined rapidly and IgG dropped to 87 AU·mL⁻¹ at the twelfth week. Elevated interleukin-6, interleukin-8, interleukin-10, interleukin-1β, interleukin-2R, and tumor necrosis factor-α levels were observed in the deceased patients in comparison with the discharged patients, and 12.5% of the association between IgG level and mortality risk was mediated by these cytokines. Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival, which may help to guide prognosis estimation.     

Preparation of Nanoporous Carbonaceous Promoters for Enhanced CO2 Absorption in Tertiary Amines

Aqueous solutions of tertiary amines are promising absorbents for CO₂ capture, as they are typically characterized by a high absorption capacity, low heat of reaction, and low corrosivity. However, tertiary amines also exhibit very low kinetics of CO₂ absorption, which has made them unattractive options for large-scale utilization. Here, a series of novel nanoporous carbonaceous promoters (NCPs) with different properties were synthesized, characterized, and used as rate promoters for CO₂ absorption in aqueous N, N-diethylethanolamine (DEEA) solutions. To prepare a DEEA–NCP nanofluid, NCPs were dispersed into aqueous 3 mol·L⁻¹ DEEA solution using ultrasonication. The results revealed that among microporous (GC) and mesoporous (GS) carbonaceous structures functionalized with ethylenediamine (EDA) and polyethyleneimine (PEI) molecules, the GC–EDA promoter exhibited the best performance. A comparison between DEEA–GC–EDA nanofluid and typical aqueous DEEA solutions highlighted that the GC-EDA promoter enhances the rate of CO₂ absorption at 40 °C by 38.6% (36.8–50.7 kPa·min⁻¹) and improves the equilibrium CO₂ absorption capacity (15 kPa; 40 °C) by 13.2% (0.69–0.78 mol of CO₂ per mole of DEEA). Moreover, the recyclability of DEEA–GC–EDA nanofluid was determined and a promotion mechanism is suggested. The outcomes demonstrate that NCP–GC–EDA in tertiary amines is a promising strategy to enhance the rate of CO₂ absorption and facilitate their large-scale deployment.     

Effect of solvent ratio on the properties of highly oriented sprayed fluorine-doped tin oxide thin films

Transparent conducting thin films of F:SnO₂ have been deposited onto preheated glass substrates by a spray pyrolysis technique using pentahydrate stannic chloride (SnCl₄·5H₂O) and ammonium fluoride (NH₄F) as precursors and mixture of water and propane-2-ol as solvent. The concentration of SnCl₄·5H₂O and NH₄F is kept fixed and the ratio of water and propane-2-ol solvent in the spraying solution is varied. A fine spray of the source solution using air as a carrier gas has grown films of thickness up to 995 nm. Optical absorption, X-ray diffraction, Van der Pauw technique for measurement of a sheet resistance and Hall effect measurements at room temperature for determination of carrier density and conductivity have been used. The as-deposited films are of polycrystalline SnO₂ with a tetragonal crystal structure and are preferentially having orientation along the (200) direction with texture coefficient as high as 6.16. The average grain size for the as-deposited sample is found to be of the order of 44 nm. The films have moderate optical transmission (up to 70–85% at 550 nm). The figure of merit (ϕ) values vary from 1.95 · 10^− 3 to 35.68 · 10^− 3 Ω^− 1. The films are heavily doped, degenerate and exhibit n-type electrical conductivity. The lowest sheet resistance (R_s) for the optimized sample is 5.1 Ω. The films have a resistivity of 5.43 · 10^− 4 Ω cm and mobility around 7.38 cm² V^− 1 s^− 1.     

Achieving Ultrahigh Volumetric Energy Storage by Compressing Nitrogen and Sulfur Dual-Doped Carbon Nanocages via Capillarity

High volumetric performance is a challenging issue for carbon-based electrical double-layer capacitors (EDLCs). Herein, collapsed N,S dual-doped carbon nanocages (cNS-CNC) are constructed by simple capillary compression, which eliminates the surplus meso- and macropores, leading to a much increased density only at the slight expense of specific surface area. The N,S dual-doping induces strong polarity of the carbon surface, and thus much improves the wettability and charge transfer. The synergism of the high density, large ion-accessible surface area, and fast charge transfer leads to state-of-the-art volumetric performance under the premise of high rate capability. At a current density of 50 A g⁻¹, the optimized cNS-CNC delivers a high volumetric capacitance of 243 and 199 F cm⁻³ in KOH and EMIMBF₄ electrolyte, with high energy density of 7.9 and 93.4 Wh L⁻¹, respectively. A top-level stack volumetric energy density of 75.3 Wh L⁻¹ (at power density of 0.7 kW L⁻¹) and a maximal stack volumetric power density of 112 kW L⁻¹ (at energy density of 18.8 Wh L⁻¹) are achieved in EMIMBF₄, comparable to the lead–acid battery in energy density but better in power density with 2–3 orders. This study demonstrates an efficient strategy to design carbon-based materials for high-volumetric-performance EDLCs with wide practical applications.     

High-efficiency separation of Ni from Cu-Ni alloy by electrorefining in choline chloride-ethylene glycol deep eutectic solvent

High-purity Cu powders (99.967%) can be obtained by the electrorefining of Cu-Ni alloy (Ni ≤ 5%) in choline chloride-ethylene glycol deep eutectic solvent (ChCl-EG DES) at near room temperature. The electrochemical separation behaviors of Cu and Ni have been investigated by linear sweep voltammetry in 0.1 M CuCl + ChCl-EG DES. The results show that the oxidation potential of Cu is more positive than that of Ni, which implies Cu and Ni can be separated by electrochemistry. And the increasing of temperature is beneficial to the decontamination of Ni from Cu-Ni alloy. Besides, the effects of current density (2–10 mA·cm⁻²) and reaction temperature (323–363 K) on the current efficiency and specific energy consumption during the electrorefining process are also analyzed, respectively. The highest current efficiency (99.89%) and the corresponding specific energy consumption (281.492 kW·h·t⁻¹) can be achieved at 10 mA·cm⁻² and 363 K. The morphologies of Cu powders change from cauliflower-like to wheat ear-like with the increasing of current density. This finding provides a theoretical guidance for the separation of Ni from Cu-Ni alloy by an eco-friendly and facile electrorefining in ChCl-EG DES.     

Capillary Evaporation on High-Dense Conductive Ramie Carbon for Assisting Highly Volumetric-Performance Supercapacitors

Conductive biomass carbon possesses unique properties of excellent conductivity and outstanding thermal stability, which can be widely used as conductive additive. However, building the high-dense conductive biomass carbon with highly graphitized microcrystals at a lower carbonization temperature is still a major challenge because of structural disorder and low crystallinity of source material. Herein, a simple capillary evaporation method to efficiently build the high-dense conductive ramie carbon (hd-CRC) with the higher tap density of 0.47 cm³ g⁻¹ than commercialized Super-C45 (0.16 cm³ g⁻¹) is reported. Such highly graphitized microcrystals of hd-CRC can achieve the high electrical conductivity of 94.55 S cm⁻¹ at the yield strength of 92.04 MPa , which is higher than commercialized Super-C45 (83.92 S cm⁻¹ at 92.04 MPa). As a demonstration, hd-CRC based symmetrical supercapacitors possess a highly volumetric energy density of 9.01 Wh L⁻¹ at 25.87 kW L⁻¹, much more than those of commercialized Super-C45 (5.06 Wh L⁻¹ and 19.30 kW L⁻¹). Remarkably, the flexible package supercapacitor remarkably presents a low leakage current of 10.27 mA and low equivalent series resistance of 3.93 mΩ. Evidently, this work is a meaningful step toward high-dense conductive biomass carbon from traditional biomass graphite carbon, greatly promoting the highly-volumetric–performance supercapacitors.     

Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study

There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes has been named coronavirus disease 2019 (COVID-19). More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was 1%–2%. No specific treatment has been reported. Herein, we examined the effects of favipiravir (FPV) versus lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million international unit (IU) twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million IU twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance median time was found for the FPV arm versus the control arm (4 d (interquartile range (IQR): 2.5–9) versus 11 d (IQR: 8–13), P < 0.001). The FPV arm also showed significant improvement in chest CT compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest CT. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse events were found in the FPV arm than in the control arm. In this open-label before-after controlled study, FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection.     

A Non-Contact Original-State Online Real-Time Monitoring Method for Complex Liquids in Industrial Processes

Failures are very common during the online real-time monitoring of large quantities of complex liquids in industrial processes, and can result in excessive resource consumption and pollution. In this study, we introduce a monitoring method capable of non-contact original-state online real-time monitoring for strongly coated, high-salinity, and multi-component liquids. The principle of the method is to establish the relationship among the concentration of the target substance in the liquid (C), the color space coordinates of the target substance at different concentrations (L¹, a¹, b¹), and the maximum absorption wavelength (λ_max); subsequently, the optimum wavelength λ_T of the liquid is determined by a high-precision scanning-type monitoring system that is used to detect the instantaneous concentration of the target substance in the flowing liquid. Unlike traditional monitoring methods and existing online monitoring methods, the proposed method does not require any pretreatment of the samples (i.e., filtration, dilution, oxidation/reduction, addition of chromogenic agent, constant volume, etc.), and it is capable of original-state online real-time monitoring. This method is employed at a large electrolytic manganese plant to monitor the Fe³⁺ concentration in the colloidal process of the plant’s aging liquid (where the concentrations of Fe³⁺, Mn²⁺, and (NH₄)₂SO₄ are 0.5–18 mg·L⁻¹, 35–39 g·L⁻¹, and 90–110 g·L⁻¹, respectively). The relative error of this monitoring method compared with an off-line laboratory monitoring is less than 2%.     

Mass-Producible,Quasi-Zero-Strain,Lattice-Water-Rich Inorganic Open-Frameworks for Ultrafast-Charging and Long-Cycling Zinc-Ion Batteries

Low-cost and high-safety aqueous Zn-ion batteries are an exceptionally compelling technology for grid-scale energy storage. However, their development has been plagued by the lack of stable cathode materials allowing fast Zn²⁺-ion insertion and scalable synthesis. Here, a lattice-water-rich, inorganic-open-framework (IOF) phosphovanadate cathode, which is mass-producible and delivers high capacity (228 mAh g⁻¹) and energy density (193.8 Wh kg⁻¹ or 513 Wh L⁻¹), is reported. The abundant lattice waters functioning as a “charge shield” enable a low Zn²⁺-migration energy barrier, (0.66 eV) even close to that of Li⁺ within LiFePO₄. This fast intrinsic ion-diffusion kinetics, together with nanostructure effect, allow the achievements of ultrafast charging (71% state of charge in 1.9 min) and an ultrahigh power density (7200 W kg⁻¹ at 107 Wh kg⁻¹). Equally important, the IOF exhibits a quasi-zero-strain feature (<1% lattice change upon (de)zincation), which ensures ultrahigh cycling durability (3000 cycles) and Coulombic efficiencies of 100%. The cell-level energy and power densities reach ≈90 Wh kg⁻¹ and ≈3320 W kg⁻¹, far surpassing commercial lead–acid, Ni–Cd, and Ni–MH batteries. Lattice-water-rich IOFs may open up new opportunities for exploring stable and fast-charging Zn-ion batteries.     

Asymmetric Hairpins DNA Encapsulated Silver Nanoclusters for In Situ Fluorescence Imaging of Fusion Gene Isoforms in Bone Marrow

Rapid and accurate imaging of the BCR/ABL fusion gene isoforms (e.g., e13a2, e14a2 and co-expression type) of chronic myeloid leukemia (CML) is of vital importance to first-line drug selection, but there is no assay that meets clinical needs (e.g., clinical kits > 18 h without isoforms information). Herein, an in situ imaging platform is developed for the rapid and accurate detection of CML fusion gene isoforms using asymmetric sequence-enhanced hairpins DNA encapsulated silver nanoclusters (ADHA) and catalyzed hairpin assembly (CHA). The specific detection of e13a2 and e14a2 fusion gene isoforms with detection limits of 19.2 am (11.558 copies µL⁻¹) and 32.56 am (19.601 copies µL⁻¹) in one-pot is achieved. The feasibility of the developed assay for real-world applications are demonstrated by one-step fluorescence imaging (40 min) of e13a2, e14a2 and co-expression type in bone marrow quantitatively (International Standard: 15.66%–168.878%) and further validated by cDNA-sequencing. This work suggests that the developed imaging platform holds great potential for rapid identification of the fusion gene isoforms and isoform related treatment monitoring.     

A modified numerical method for the accurate calculation of molecular flow transmission probabilities and density distributions of cylindrical tubes

Accurate numerical calculations of molecular flow transmission probabilities and density distributions of tubes are important to the benchmark problems of Monte Carlo solutions, dynamic expansion vacuum gauge calibration systems, and molecular beam formation studies. Although Nawyn and Meyer [published by van Essen and Heerens. J Vac Sci Technol 1976; 13:1183] have solved cylindrical tube problems by using the numerical method based on Clausing's equations, perhaps the calculated results still lack sufficient accuracy. In this paper, we propose a modified method that could achieve calculation accuracies of transmission probabilities as high as 10⁻¹¹–10⁻¹³ in the range of L′/R ≤ 100 (where L′ is the tube length, R is the tube radius), which are more accurate than the results recently reported by Mohan et al. [J Vac Sci Technol A 2007; 25:758] and Gómez-Goñi et al. [J Vac Sci Technol A 2003; 21:1452].     

High-Affinity Decoy PD-1 Mutant Screened from an Epitope-Specific Cell Library

Immunotherapy with anti-programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) monoclonal antibodies has become routine in the treatment of many kinds of human cancers, such as lung cancer, intestinal cancer, and melanoma. The PD-1/PD-L1 pathway inhibits T cell activation in the micro-environment, making it an attractive target against cancer. Wild-type (WT) PD-1 ectodomain has been shown to have difficulty blocking PD-1/PD-L1 mixture formation due to its low affinity. The present work uses three-dimensional (3D) crystal complex structures to analyze the interaction by which PD-1 binds to PD-L1 or PD-L2. It also reports on a theoretical study of the binding mode between PD-1 and its clinical antibody Opdivo. Based on the theoretical binding analysis of PD-1 and its ligands (i.e., PD-L1 and PD-L2) or antibody (Opdivo), a small-content, epitope-oriented mammalian cell library was established for PD-1. After three rounds of cell sorting, the decoy PD-1 mutant 463, which presented a higher affinity than WT PD-1 to the PD-L1 (the affinity has increased by almost three orders of magnitude) was screened out. It exhibited an inhibitory effect against PD-1 to prevent it from forming mixtures with PD-L1, which was similar to the effect of the commercial anti-PD-L1 antibody atezolizumab (ATE). The median effective concentration (EC₅₀) value of the decoy mutant was 0.031 μg·mL⁻¹ in comparison with 0.063 μg·mL⁻¹ for ATE; both values were much lower than that of WT PD-1, at 2.571 μg·mL⁻¹. The 463 decoy mutant reversed the inhibitory function of PD-1 in T cell activation; furthermore, 10 mg·kg⁻¹ of 463 inhibited about 75% of tumor growth in vivo in a MC38 transgenic xenograft mice model, which was similar to the activity of ATE. More interestingly, an even lower dose of 463 (2 mg·kg⁻¹) showed a better effect than 10 mg·kg⁻¹ of WT PD-1. This work offers the decoy 463 with an improved curative effect, which holds potential to become a good option against PD-1/PD-L1-related cancers.     

Structure and magnetism in Pr3RuO7

The crystal structure of the ordered fluorite, Pr₃RuO₇, was refined from powder neutron diffraction data in Cmcm. An interesting structural feature is the presence of relatively well separated zig-zag chains of corner sharing RuO₆ octahedra, Ru–Ru interchain distance 6.61 Å vs. Ru–Ru intrachain distance of 3.76 Å. Magnetic susceptibility data show a Curie–Weiss behavior for T>225 K with C=5.96(4) emu K mol⁻¹ and θ_c=+11(2) K. In an attempt to separate the contributions of Pr(3+) and Ru(5+), the properties of isostructural Pr₃TaO₇ were also measured, yielding C=4.63(3) emu K mol⁻¹. Thus, the contribution of Ru(5+), 4d³, S=3/2, to the measured Curie constant is estimated to be 1.33 emu K mol⁻¹, not far from the spin-only value of 1.87 emu K mol⁻¹. This supports the view that the Ru 4d electrons are localized and magnetic, not itinerant. A susceptibility maximum at about 50 K is attributed to long-range magnetic order and this is substantiated by neutron diffraction data. There is little evidence for one-dimensional antiferromagnetic correlations in this material but behavior characteristic of short-range ferromagnetic correlations attributed to Pr–Ru exchange interactions are found in the temperature range 50–200 K, consistent with the positive θ_c.