MVSF-AB: Accurate antibody-antigen binding affinity prediction via multi-view sequence feature learning.

MOTIVATION: Predicting the binding affinity between antigens and antibodies accurately is crucial for assessing therapeutic antibody effectiveness and enhancing antibody engineering and vaccine design. Traditional machine learning methods have been widely used for this purpose, relying on interfacial amino acids' structural information. Nevertheless, due to technological limitations and high costs of acquiring structural data, the structures of most antigens and antibodies are unknown, and sequence-based methods have gained attention. Existing sequence-based approaches designed for protein-protein affinity prediction exhibit a significant drop in performance when applied directly to antibody-antigen affinity prediction due to imbalanced training data and lacking design in the model framework specifically for antibody-antigen, hindering the learning of key features of antibodies and antigens. Therefore, we propose MVSF-AB, a Multi-View Sequence Feature learning for accurate Antibody-antigen Binding affinity prediction. RESULTS: MVSF-AB designs a multi-view method that fuses semantic features and residue features to fully utilize the sequence information of antibody-antigen and predicts the binding affinity. Experimental results demonstrate that MVSF-AB outperforms existing approaches in predicting unobserved natural antibody-antigen affinity and maintains its effectiveness when faced with mutant strains of antibodies. AVAILABILITY AND IMPLEMENTATION: Datasets we used and source code are available on our public GitHub repository https://github.com/TAI-Medical-Lab/MVSF-AB.

Ume6-dependent pathways of morphogenesis and biofilm formation in Candida auris.

Candida auris is a yeast pathogen causing nosocomial outbreaks of candidemia. Its ability to adhere to inert surfaces and to be transmitted from one patient to another via medical devices is of particular concern. Like other Candida spp., C. auris has the ability to transition from the yeast form to pseudohyphae and to build biofilms. Moreover, some isolates have a unique capacity to form aggregates. These morphogenetic changes may impact virulence. In this study, we demonstrated the role of the transcription factor Ume6 in C. auris morphogenesis. Genetic hyperactivation of Ume6 induced filamentation and aggregation. The Ume6-hyperactivated strain (UME6HA) also exhibited increased adhesion to inert surface and formed biofilms of higher biomass compared to the parental strain. Transcriptomic analyses of UME6HA revealed enrichment of genes encoding for adhesins, proteins involved in cell wall organization, sterol biosynthesis, and aspartic protease activities. The three most upregulated genes compared to wild-type were those encoding for the agglutin-like sequence adhesin Als4498, the C. auris-specific adhesin Scf1, and the hypha-specific G1 cyclin-related protein Hgc1. The deletion of these genes in the UME6HA background showed that Ume6 controls filamentation via Hgc1 and aggregation via Als4498 and Scf1. Adhesion to inert surface was essentially triggered by Scf1. However, Als4498 and Hgc1 were also crucial for biofilm formation. Our data show that Ume6 is a universal regulator of C. auris morphogenesis via distinct modulators.IMPORTANCEC. auris represents a public health threat because of its ability to cause difficult-to-treat infections and hospital outbreaks. The morphogenetic plasticity of C. auris, including its ability to filament, to form aggregates or biofilms on inert surfaces, is important to the fungus for interhuman transmission, skin or catheter colonization, tissue invasion, antifungal resistance, and escape of the host immune system. This work deciphered the importance of Ume6 in the control of distinct pathways involved in filamentation, aggregation, adhesion, and biofilm formation of C. auris. A better understanding of the mechanisms of C. auris morphogenesis may help identify novel antifungal targets.

Multivalent Pt/Ti3C2Tx Nanocomposite-Based Immunochromatographic Sensor for Colorimetric/Temperature/Pressure Trimodal Detection.

Multimodal immunochromatographic sensors (ICSs) have acquired extensive attention since they not only provide reliable results by comparing the different output signals but also flexibly respond to various application environments. Herein, an ICS with triple signal outputs including colorimetry, temperature, and pressure was developed for sensitive detection of chlorothalonil. The multivalent Pt/Ti3C2Tx nanoparticles as signal tags were facilely synthesized by loading PtNPs onto single-layer Ti3C2Tx nanosheets with high surface area. The acquired Pt/Ti3C2TxNPs accelerated the rate-limiting step of the aerogenesis reaction of H2O2 for producing intensive pressure signals due to their significant catalase-mimic activity. Meanwhile, they showed desirable photothermal conversion efficiency in the near-infrared region for producing significant temperature signals. Furthermore, their deep color also allowed facile colorimetry by using the naked eye. Based on a competitive immunoassay, chlorothalonil was detected as a model analyte on this trimodal ICS platform. The detection limits for pressure, temperature, and colorimetric modes were 0.04, 0.09, and 5 ng mL-1, respectively. The recoveries for detecting chlorothalonil supplemented in Astragalus and Honeysuckle with pressure mode were 84.0-110% and 108-114%, respectively. Therefore, the ICS presented a portable, sensitive, accurate, and flexible multimodal strategy suitable for point-of-care testing.

Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals.

Fluorescent genetically encoded voltage indicators report transmembrane potentials of targeted cell-types. However, voltage-imaging instrumentation has lacked the sensitivity to track spontaneous or evoked high-frequency voltage oscillations in neural populations. Here we describe two complementary TEMPO voltage-sensing technologies that capture neural oscillations up to ~100 Hz. Fiber-optic TEMPO achieves ~10-fold greater sensitivity than prior photometry systems, allows hour-long recordings, and monitors two neuron-classes per fiber-optic probe in freely moving mice. With it, we uncovered cross-frequency-coupled theta- and gamma-range oscillations and characterized excitatory-inhibitory neural dynamics during hippocampal ripples and visual cortical processing. The TEMPO mesoscope images voltage activity in two cell-classes across a ~8-mm-wide field-of-view in head-fixed animals. In awake mice, it revealed sensory-evoked excitatory-inhibitory neural interactions and traveling gamma and 3-7 Hz waves in the visual cortex, and previously unreported propagation directions for hippocampal theta and beta waves. These technologies have widespread applications probing diverse oscillations and neuron-type interactions in healthy and diseased brains.

Dopamine-mediated interactions between short- and long-term memory dynamics.

In dynamic environments, animals make behavioural decisions on the basis of the innate valences of sensory cues and information learnt about these cues across multiple timescales1-3. However, it remains unclear how the innate valence of a sensory stimulus affects the acquisition of learnt valence information and subsequent memory dynamics. Here we show that in the Drosophila brain, interconnected short- and long-term memory units of the mushroom body jointly regulate memory through dopamine signals that encode innate and learnt sensory valences. By performing time-lapse in vivo voltage-imaging studies of neural spiking in more than 500 flies undergoing olfactory associative conditioning, we found that protocerebral posterior lateral 1 dopamine neurons (PPL1-DANs)4 heterogeneously and bidirectionally encode innate and learnt valences of punishment, reward and odour cues. During learning, these valence signals regulate memory storage and extinction in mushroom body output neurons (MBONs)5. During initial conditioning bouts, PPL1-γ1pedc and PPL1-γ2α'1 neurons control short-term memory formation, which weakens inhibitory feedback from MBON-γ1pedc>α/ß to PPL1-α'2α2 and PPL1-α3. During further conditioning, this diminished feedback allows these two PPL1-DANs to encode the net innate plus learnt valence of the conditioned odour cue, which gates long-term memory formation. A computational model constrained by the fly connectome6,7 and our spiking data explains how dopamine signals mediate the circuit interactions between short- and long-term memory traces, yielding predictions that our experiments confirmed. Overall, the mushroom body achieves flexible learning through the integration of innate and learnt valences in parallel learning units sharing feedback interconnections. This hybrid physiological-anatomical mechanism may be a general means by which dopamine regulates memory dynamics in other species and brain structures, including the vertebrate basal ganglia.

Point-of-care testing of Pseudomonas aeruginosa using PCN-222(Pt) prepared by nanoconfinement-guided protocol to catalyze gas generation reaction.

BACKGROUND: Pathogenic bacteria are keeping threatening global public health since they can cause many infectious diseases. The traditional microorganism identification and molecular diagnostic techniques are insufficiently sensitive, time-consuming, or expensive. Thus it is of great interest to establish pressure signal-based sensing platforms for point-of-care testing of pathogenic bacteria to achieve timely diagnosis of infectious diseases. Rational design and synthesis of nano-sized probes with high peroxidase-mimicking activity have been a long-term cherished goal for improving the sensitivity of pressure signal-based sensing methods. RESULTS: Guided by nanoconfinement effect, PCN-222(Pt) was prepared by confining Pt clusters within the channels of a zirconium porphyrin MOFs material termed as PCN-222. In comparison to regular platinum nanoparticles, palladium@platinum core-shell nanodendrites, and platinum-coated gold nanoparticles, the prepared PCN-222(Pt) displayed superior peroxidase-mimicking activity with outstanding efficiency for catalyzing the decay of H2O2 to produce O2. Thus it was used as a pressure signal probe to establish a sensitive method on a hydrogel pellets platform for analyzing Pseudomonas aeruginosa (P. aeruginosa), for which polymyxin B and a phage termed as JZ1 were used as recognition agents for the target pathogen. P. aeruginosa was quantified with a handheld pressure meter within a broad range of 2.2 × 102-2.2 × 107 cfu mL-1. This method was used to quantify P. aeruginosa in various biological and food samples with acceptable accuracy and reliability. SIGNIFICANCE: The proposed nanoconfinement-guided protocol provides a novel approach for rational design and preparation of nano-sized probes with high peroxidase-mimicking activity for catalyzing gas-generation reaction. Thus this study opens an avenue for establishment of sensitive pressure signal-based sensing methods for pathogenic bacteria, which shows broad application prospects in medical diagnosis of infectious diseases.

The interplay of hematite and photic biofilm triggers the acceleration of biotic nitrate removal.

The soil-water interface is replete with photic biofilm and iron minerals; however, the potential of how iron minerals promote biotic nitrate removal is still unknown. This study investigates the physiological and ecological responses of photic biofilm to hematite (Fe2O3), in order to explore a practically feasible approach for in-situ nitrate removal. The nitrate removal by photic biofilm was significantly higher in the presence of Fe2O3 (92.5%) compared to the control (82.8%). Results show that the presence of Fe2O3 changed the microbial community composition of the photic biofilm, facilitates the thriving of Magnetospirillum and Pseudomonas, and promotes the growth of photic biofilm represented by the extracellular polymeric substance (EPS) and the content of chlorophyll. The presence of Fe2O3 also induces oxidative stress (•O2-) in the photic biofilm, which was demonstrated by electron spin resonance spectrometry. However, the photic biofilm could improve the EPS productivity to prevent the entrance of Fe2O3 to cells in the biofilm matrix and mitigate oxidative stress. The Fe2O3 then promoted the relative abundance of Magnetospirillum and Pseudomonas and the activity of nitrate reductase, which accelerates nitrate reduction by the photic biofilm. This study provides an insight into the interaction between iron minerals and photic biofilm and demonstrates the possibility of combining biotic and abiotic methods to improve the in-situ nitrate removal rate.

Microplastic coupled with soil dissolved organic matter mediated changes in the soil chemical and microbial characteristics.

The abundance of microplastics (MPs) in soil environments has attracted significant attentions, due to their impact on soil physico-chemical properties. However, limited information is available on the influences of MPs on soil carbon composition and microbial utilization characteristics. Therefore, a two-month incubation experiment was conducted to add polyethylene microplastics (PE-MPs) with different levels (1%, 10%) and sizes (150-300 µm and 75-150 µm) into different soils. After that, soil chemical properties including the dissolved organic carbon (DOC), spectral characteristics of dissolved organic matter (DOM) and soil microbial characteristics were analyzed. Results revealed that PE-MPs addition caused significant differences in soil chemical properties between farmland and woodland soils, particularly in soil pH, DOM composition, and soil phosphatase activity. Woodland soil always exhibited higher levels of DOC content, microbial diversity, and soil carbon source utilization compared to farmland soil, leading to increased humification in the DOM of woodland soil. PE-MPs with a larger particle size significantly increased both the soil DOC content and enzyme activity. Addition of PE-MPs altered the soil DOM composition, and the fluorescence parameters like the biological index (BIX) and humification degree. Moreover, the carbon source utilization intensity of microorganisms on PE MPs-contaminated soils is higher in woodland soils. Various analyses confirmed that compared to other soil properties, characteristics of soil DOM had a more significant impact on soil microbial community composition. Thus, PE-MPs in conjunction with soil DOM spectral characteristics regulated soil microbial diversity, which is crucial for understanding soil carbon sequestration.

A Coarse-Fine Collaborative Learning Model for Three Vessel Segmentation in Fetal Cardiac Ultrasound Images.

Congenital heart disease (CHD) is the most frequent birth defect and a leading cause of infant mortality, emphasizing the crucial need for its early diagnosis. Ultrasound is the primary imaging modality for prenatal CHD screening. As a complement to the four-chamber view, the three-vessel view (3VV) plays a vital role in detecting anomalies in the great vessels. However, the interpretation of fetal cardiac ultrasound images is subjective and relies heavily on operator experience, leading to variability in CHD detection rates, particularly in resource-constrained regions. In this study, we propose an automated method for segmenting the pulmonary artery, ascending aorta, and superior vena cava in the 3VV using a novel deep learning network named CoFi-Net. Our network incorporates a coarse-fine collaborative strategy with two parallel branches dedicated to simultaneous global localization and fine segmentation of the vessels. The coarse branch employs a partial decoder to leverage high-level semantic features, enabling global localization of objects and suppression of irrelevant structures. The fine branch utilizes attention-parameterized skip connections to improve feature representations and improve boundary information. The outputs of the two branches are fused to generate accurate vessel segmentations. Extensive experiments conducted on a collected dataset demonstrate the superiority of CoFi-Net compared to state-of-the-art segmentation models for 3VV segmentation, indicating its great potential for enhancing CHD diagnostic efficiency in clinical practice. Furthermore, CoFi-Net outperforms other deep learning models in breast lesion segmentation on a public breast ultrasound dataset, despite not being specifically designed for this task, demonstrating its potential and robustness for various segmentation tasks.

Alleviation of allergic asthma by rosmarinic acid via gut-lung axis.

BACKGROUND: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. PURPOSE: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. METHODS: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. RESULTS: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. CONCLUSIONS: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.

Upc2-mediated mechanisms of azole resistance in Candida auris.

Candida auris is an emerging yeast pathogen of major concern because of its ability to cause hospital outbreaks of invasive candidiasis and to develop resistance to antifungal drugs. A majority of C. auris isolates are resistant to fluconazole, an azole drug used for the treatment of invasive candidiasis. Mechanisms of azole resistance are multiple, including mutations in the target gene ERG11 and activation of the transcription factors Tac1b and Mrr1, which control the drug transporters Cdr1 and Mdr1, respectively. We investigated the role of the transcription factor Upc2, which is known to regulate the ergosterol biosynthesis pathway and azole resistance in other Candida spp. Genetic deletion and hyperactivation of Upc2 by epitope tagging in C. auris resulted in drastic increases and decreases in susceptibility to azoles, respectively. This effect was conserved in strains with genetic hyperactivation of Tac1b or Mrr1. Reverse transcription PCR analyses showed that Upc2 regulates ERG11 expression and also activates the Mrr1/Mdr1 pathway. We showed that upregulation of MDR1 by Upc2 could occur independently from Mrr1. The impact of UPC2 deletion on MDR1 expression and azole susceptibility in a hyperactive Mrr1 background was stronger than that of MRR1 deletion in a hyperactive Upc2 background. While Upc2 hyperactivation resulted in a significant increase in the expression of TAC1b, CDR1 expression remained unchanged. Taken together, our results showed that Upc2 is crucial for azole resistance in C. auris, via regulation of the ergosterol biosynthesis pathway and activation of the Mrr1/Mdr1 pathway. Notably, Upc2 is a very potent and direct activator of Mdr1.IMPORTANCECandida auris is a yeast of major medical importance causing nosocomial outbreaks of invasive candidiasis. Its ability to develop resistance to antifungal drugs, in particular to azoles (e.g., fluconazole), is concerning. Understanding the mechanisms of azole resistance in C. auris is important and may help in identifying novel antifungal targets. This study shows the key role of the transcription factor Upc2 in azole resistance of C. auris and shows that this effect is mediated via different pathways, including the regulation of ergosterol biosynthesis and also the direct upregulation of the drug transporter Mdr1.

Phages modified hydrogel pellet assembled in 3D printed both-in-one device for detecting Pseudomonas aeruginosa based on colorimetric and pressure readout modes.

Pseudomonas aeruginosa (P. aeruginosa) with noticeable drug-resistance profile is one of the most pernicious pathogens that attracts major public health concerns. Herein, a 3D printed device combined with hydrogel pellet modified with phages was designed for point-of-care testing (POCT) of this pathogen with both colorimetric and pressure readout modes. A P. aeruginosa phage belonging to the family of Podoviridae was isolated from river water and noted as vB_PaeP-JZ1 (JZ1). Due to its host specificity, phage JZ1 was used as a recognizing agent for modifying the hydrogel pellet, and the modified hydrogel pellet was assembled into the 3D printed device to act as the sensing interface. Polymyxin B (PMB) was tagged with Pd@Pt core-shell nanodendrites (Pd@PtNDs) showing excellent peroxidase-like activity to act as the colorimetric and pressure signal tracer. P. aeruginosa can be quantified within the concentration ranges of 2.6 × 103 cfu mL-1 - 2.6 × 108 cfu mL-1 and 2.6 × 102 cfu mL-1 - 2.6 × 107 cfu mL-1 with colorimetric and pressure readout modes, respectively. The both modes can achieve quantitation of P. aeruginosa within 25 min. Thus the "both-in-one" 3D printed device with dual-mode readout function offers a rapid, sensitive, and specific platform for POCT of pathogenic bacteria.

Reduced arsenic availability in paddy soil through Fe-organic ligand complexation mediated by bamboo biochar.

The reuse of arsenic (As)-contaminated paddy fields is a global challenge because long-term flooding would result in As release due to the reductive dissolution of iron minerals. Biochar amendment is a common and effective remediation technique for As-contaminated paddy soil. However, the literature is still lacking in systematic research on the function of biochar in controlling the complexation of released dissolved organic matter (DOM) and iron oxides and its synergistic impact on the availability of As in flooded paddy soil. In the present study, bamboo biochar was prepared at different pyrolysis temperatures (300, 450 and 600 °C), as BB300, BB450 and BB600. Four paddy soil treatments including BB300, BB450, BB600 applications (1% ratio, m/m, respectively) and control (CK, no biochar application) were set and incubated for 60 d in flooding condition. The results showed that As availability represented by adsorbed As species (A-As) was mitigated by BB450 amendment compared with CK. The amendment of BB450 in paddy soil facilitated the complexation of HCl extractable Fe(III)/(II) and DOM and formation of amorphous iron oxides (e.g. complexed Fe species). Moreover, the abundance of Geobacteraceae and Xanthomonadaceae, as common electroactive bacteria, was promoted in the BB450 treated paddy soil in comparison to CK, which assisted to form amorphous iron oxides. The formed amorphous iron oxides then facilitated the formation of ternary complex (As-Fe-DOM) with highly stability, which could be considered as a mechanism for As immobilization after biochar was applied to the flooding paddy soil. Thus, the synergistic effect between amorphous iron oxides and electroactive stains could make main contribution to the passivation of released As in paddy soil under long-term flooding condition. This study provided a new insight for As immobilization via regulating iron-organic ligand complexation amendment with biochar in flooding paddy soil.

Robust retrieval of material chemical states in X-ray microspectroscopy.

X-ray microspectroscopic techniques are essential for studying morphological and chemical changes in materials, providing high-resolution structural and spectroscopic information. However, its practical data analysis for reliably retrieving the chemical states remains a major obstacle to accelerating the fundamental understanding of materials in many research fields. In this work, we propose a novel data formulation model for X-ray microspectroscopy and develop a dedicated unmixing framework to solve this problem, which is robust to noise and spectral variability. Moreover, this framework is not limited to analyzing two-state material chemistry, making it an effective alternative to conventional and widely used methods. In addition, an alternative directional multiplier method with explicit or implicit regularization is applied to obtain the solution efficiently. Our framework can accurately identify and characterize chemical states in complex and heterogeneous samples, even under challenging conditions such as low signal-to-noise ratios and overlapping spectral features. By testing six simulated datasets, our method improves the existing methods by up to 151.84% and 136.33% in terms of the peak signal-to-noise ratio (PSNR) and the structural similarity index (SSIM) for the chemical phase map. Extensive experimental results on simulated and real datasets demonstrate its effectiveness and reliability.

Rapid and signal crowdedness-robust in situ sequencing through hybrid block coding.

Spatial transcriptomics technology has revolutionized our understanding of cell types and tissue organization, opening possibilities for researchers to explore transcript distributions at subcellular levels. However, existing methods have limitations in resolution, sensitivity, or speed. To overcome these challenges, we introduce SPRINTseq (Spatially Resolved and signal-diluted Next-generation Targeted sequencing), an innovative in situ sequencing strategy that combines hybrid block coding and molecular dilution strategies. Our method enables fast and sensitive high-resolution data acquisition, as demonstrated by recovering over 142 million transcripts using a 108-gene panel from 453,843 cells from four mouse brain coronal slices in less than 2 d. Using this advanced technology, we uncover the cellular and subcellular molecular architecture of Alzheimer's disease, providing additional information into abnormal cellular behaviors and their subcellular mRNA distribution. This improved spatial transcriptomics technology holds great promise for exploring complex biological processes and disease mechanisms.

Nanoscale chemical imaging with structured X-ray illumination.

High-resolution imaging with compositional and chemical sensitivity is crucial for a wide range of scientific and engineering disciplines. Although synchrotron X-ray imaging through spectromicroscopy has been tremendously successful and broadly applied, it encounters challenges in achieving enhanced detection sensitivity, satisfactory spatial resolution, and high experimental throughput simultaneously. In this work, based on structured illumination, we develop a single-pixel X-ray imaging approach coupled with a generative image reconstruction model for mapping the compositional heterogeneity with nanoscale resolvability. This method integrates a full-field transmission X-ray microscope with an X-ray fluorescence detector and eliminates the need for nanoscale X-ray focusing and raster scanning. We experimentally demonstrate the effectiveness of our approach by imaging a battery sample composed of mixed cathode materials and successfully retrieving the compositional variations of the imaged cathode particles. Bridging the gap between structural and chemical characterizations using X-rays, this technique opens up vast opportunities in the fields of biology, environmental, and materials science, especially for radiation-sensitive samples.

The effect of random virus failure following cell entry on infection outcome and the success of antiviral therapy.

A virus infection can be initiated with very few or even a single infectious virion, and as such can become extinct, i.e. stochastically fail to take hold or spread significantly. There are many ways that a fully competent infectious virion, having successfully entered a cell, can fail to cause a productive infection, i.e. one that yields infectious virus progeny. Though many stochastic models (SMs) have been developed and used to estimate a virus infection's establishment probability, these typically neglect infection failure post virus entry. The SM presented herein introduces parameter [Formula: see text] which corresponds to the probability that a virion's entry into a cell will result in a productive cell infection. We derive an expression for the likelihood of infection establishment in this new SM, and find that prophylactic therapy with an antiviral reducing [Formula: see text] is at least as good or better at decreasing the establishment probability, compared to antivirals reducing the rates of virus production or virus entry into cells, irrespective of the SM parameters. We investigate the difference in the fraction of cells consumed by so-called extinct versus established virus infections, and find that this distinction becomes biologically meaningless as the probability of establishment approaches zero. We explain why the release of virions continuously over an infectious cell's lifespan, rather than as a single burst at the end of the cell's lifespan, does not result in an increased risk of infection extinction. We show, instead, that the number of virus released, not the timing of the release, affects infection establishment and associated critical antiviral efficacy.

Preparation of CH3NH3PbBr3 Perovskites Encapsulated in ZIF-8 with Improved Stability and Their Application in Fluorimetry and Information Encryption.

Metal halide perovskites (MHPs) have been promising functional materials for developing solar cells, lasers, photodetectors, and sensors due to their outstanding optical and electrical characteristics. However, they suffer from very poor stability for their high sensitivity to some environmental factors such as temperature, UV irradiation, pH, and polar solvent, which limits their extensive practical applications. Herein, a derived metal organic framework material, Pb-ZIF-8, was prepared as a precursor via a doping protocol. Then, CH3NH3PbBr3 perovskites encapsulated in ZIF-8 (CH3NH3PbBr3@ZIF-8) with green fluorescent (FL) emission were synthesized via a facile in situ protocol by using the derived metal organic frameworks material as a source of Pb element. With the protection of encapsulated ZIF-8, the perovskites material shows good FL properties under various harsh environmental conditions, which facilitates facile application in various fields. To verify the practical application potential of CH3NH3PbBr3@ZIF-8, we utilized them as FL probes to establish a highly sensitive method for detecting glutathione. Furthermore, the rapid conversion process from non-FL Pb-ZIF-8 to FL CH3NH3PbBr3@ZIF-8 was utilized to realize encryption and decryption of confidential information. This work opens an avenue to the development of perovskites-based devices with greatly improved stability in harsh external environments.

Novel ERG11 and TAC1b mutations associated with azole resistance in Candida auris.

Candida auris is a novel Candida species that has spread in all continents causing nosocomial outbreaks of invasive candidiasis. C. auris has the ability to develop resistance to all antifungal drug classes. Notably, many C. auris isolates are resistant to the azole drug fluconazole, a standard therapy of invasive candidiasis.Azole resistance in C. auris can result from mutations in the azole target gene ERG11 and/or overexpression of the efflux pump Cdr1. TAC1 is a transcription factor controlling CDR1 expression in C. albicans The role of TAC1 homologs in C. auris (TAC1a and TAC1b) remains to be better defined.In this study, we compared sequences of ERG11, TAC1a and TAC1b between a fluconazole-susceptible and five fluconazole-resistant C. auris isolates of clade IV. Among four of the resistant isolates, we identified a similar genotype with concomitant mutations in ERG11 (F444L) and TAC1b (S611P). The simultaneous deletion of tandemly arranged TAC1a/TAC1b resulted in a decrease of minimal inhibitory concentration (MIC) for fluconazole. Introduction of the ERG11 and TAC1b mutations separately and/or combined in the wild-type azole susceptible isolate resulted in a significant increase of azole resistance with a cumulative effect of the two combined mutations. Interestingly, CDR1 expression was not significantly affected by TAC1a/TAC1b deletion or by the presence of the TAC1b S611P mutation, suggesting the existence of Tac1-dependent and Cdr1-independent azole resistance mechanisms.We demonstrated the role of two previously unreported mutations responsible for azole resistance in C. auris, which were a common signature among four azole-resistant isolates of clade IV.

Smartphone-Based Pressure Signal Readout Device Combined with Bidirectional Immunochromatographic Test Strip for Dual-Analyte Detection.

Pressure has been a facile signal readout mode for developing point-of-care testing devices due to the attractive features of portability, accessibility, rapidity, and affordability. Herein, a pressure signal readout device was designed by integrating two homemade needle-type piezoresistive transducers, a controller for a thin-film piezoresistive sensor and a smartphone. Meanwhile, a bidirectional immunochromatographic test strip was designed as an immunoreaction platform for dual-analyte detection. Using PdCuPt nanoparticles with catalase-mimic activity as signal tags, the pressure signals triggered by catalyzed aerogenous reaction were monitored by the pressure signal readout device and read on a smartphone with the Bluetooth module. In this proof-of-principle work, imidacloprid and carbendazim were detected as model analytes. The dynamic ranges for quantitating imidacloprid and carbendazim are 20 pg mL-1 to 50 ng mL-1 and 50 pg mL-1 to 50 ng mL-1, respectively. The whole immunoassay process was completed within 16 min. The recovery values for imidacloprid and carbendazim spiked into herbal medicines are 82.0-110.0 and 84.0-116.0%, respectively, verifying its reliability for real sample detection. As the smartphone APP and controller for a thin-film piezoresistive sensor contain 12 signal channels, the system can be easily extended to meet the demand for high-throughput screening.