Ultrafast Mueller matrix polarimetry with 10 nanosecond temporal resolution based on optical time-stretch.

A fastest full Mueller matrix polarimeter, to the best of our knowledge, based on optical time-stretch has been proposed and demonstrated. Thanks to the time-stretch-based ultrafast spectra detection mechanism, its measurement time could reach 10 ns. Additionally, a novel, to the best of aour knowledge, simpler method to estimate its main systematic error has been proposed and verified. With the proposed method, static measurement of polarizer and wave plate is executed with a maximum coefficient error of below 0.1. Dynamic measurement of a free space electro-optic modulator as fast-changing phase retardation has also been executed to demonstrate the feasibility of the proposed system.

OSNR monitoring based on a low-bandwidth coherent receiver and LSTM classifier.

Optical signal-to-noise ratio (OSNR) monitoring is one of the core tasks of advanced optical performance monitoring (OPM) technology, which plays an essential role in future intelligent optical communication networks. In contrast to many regression-based methods, we convert the continuous OSNR monitoring into a classification problem by restricting the outputs of the neural network-based classifier to discrete OSNR intervals. We also use a low-bandwidth coherent receiver for obtaining the time domain samples and a long short-term memory (LSTM) neural network as the chromatic dispersion-resistant classifier. The proposed scheme is cost efficient and compatible with our previously proposed multi-purpose OPM platform. Both simulation and experimental verification show that the proposed OSNR monitoring technique achieves high classification accuracy and robustness with low computational complexity.

Versatile biomanufacturing through stimulus-responsive cell-material feedback.

Small-scale production of biologics has great potential for enhancing the accessibility of biomanufacturing. By exploiting cell-material feedback, we have designed a concise platform to achieve versatile production, analysis and purification of diverse proteins and protein complexes. The core of our technology is a microbial swarmbot, which consists of a stimulus-sensitive polymeric microcapsule encapsulating engineered bacteria. By sensing the confinement, the bacteria undergo programmed partial lysis at a high local density. Conversely, the encapsulating material shrinks responding to the changing chemical environment caused by cell growth, squeezing out the protein products released by bacterial lysis. This platform is then integrated with downstream modules to enable quantification of enzymatic kinetics, purification of diverse proteins, quantitative control of protein interactions and assembly of functional protein complexes and multienzyme metabolic pathways. Our work demonstrates the use of the cell-material feedback to engineer a modular and flexible platform with sophisticated yet well-defined programmed functions.

A noisy linear map underlies oscillations in cell size and gene expression in bacteria.

During bacterial growth, a cell approximately doubles in size before division, after which it splits into two daughter cells. This process is subjected to the inherent perturbations of cellular noise and thus requires regulation for cell-size homeostasis. The mechanisms underlying the control and dynamics of cell size remain poorly understood owing to the difficulty in sizing individual bacteria over long periods of time in a high-throughput manner. Here we measure and analyse long-term, single-cell growth and division across different Escherichia coli strains and growth conditions. We show that a subset of cells in a population exhibit transient oscillations in cell size with periods that stretch across several (more than ten) generations. Our analysis reveals that a simple law governing cell-size control-a noisy linear map-explains the origins of these cell-size oscillations across all strains. This noisy linear map implements a negative feedback on cell-size control: a cell with a larger initial size tends to divide earlier, whereas one with a smaller initial size tends to divide later. Combining simulations of cell growth and division with experimental data, we demonstrate that this noisy linear map generates transient oscillations, not just in cell size, but also in constitutive gene expression. Our work provides new insights into the dynamics of bacterial cell-size regulation with implications for the physiological processes involved.

Complete genome analysis of PaGz-1 and PaZq-1, two novel phages belonging to the genus Pakpunavirus.

Pseudomonas phages PaGz-1 and PaZq-1, two new phages infecting Pseudomonas aeruginosa, were isolated from fresh water in Guangdong province, China. The genomes of these two phages consist of 93,975 bp and 94,315 bp and contain 175 and 172 open reading frames (ORFs), respectively. The genome sequences of PaGz-1 and PaZq-1 share 95.8% identity with a query coverage of 94%, suggesting that these two phages belong to two different species. Based on results of nucleotide sequence alignment, gene annotation, and phylogenetic analysis, we propose PaGz-1 and PaZq-1 as representative isolates of two species in the genus Pakpunavirus within the family Myoviridae.

Drug detoxification dynamics explain the postantibiotic effect.

The postantibiotic effect (PAE) refers to the temporary suppression of bacterial growth following transient antibiotic treatment. This effect has been observed for decades for a wide variety of antibiotics and microbial species. However, despite empirical observations, a mechanistic understanding of this phenomenon is lacking. Using a combination of modeling and quantitative experiments, we show that the PAE can be explained by the temporal dynamics of drug detoxification in individual cells after an antibiotic is removed from the extracellular environment. These dynamics are dictated by both the export of the antibiotic and the intracellular titration of the antibiotic by its target. This mechanism is generally applicable for antibiotics with different modes of action. We further show that efflux inhibition is effective against certain antibiotic motifs, which may help explain mixed cotreatment success.

Complete genome analysis of bacteriophage AsXd-1, a new member of the genus Hk97virus, family Siphoviridae.

AsXd-1, a bacteriophage that infects Aeromonas salmonicida, was isolated from the wastewater of a seafood market in Shenzhen, China. The 39,014-bp genome of this phage contains 52 open reading frames (ORFs), 30 of which were found to be homologous to reference sequences that putatively encode functional phage proteins. Nine out of the remaining 22 ORFs with unknown functions were unique to AsXd-1. Gene annotation suggests that AsXd-1 has both lysogenic and lytic life cycles. Furthermore, both phylogenetic analysis based on the large subunit of terminase and genome sequence comparisons show that AsXd-1 is closely related to phages belonging to the genus Hk97virus. We thus propose AsXd-1 as a new member of the genus Hk97virus within the family Siphoviridae.

Coupling spatial segregation with synthetic circuits to control bacterial survival.

Engineered bacteria have great potential for medical and environmental applications. Fulfilling this potential requires controllability over engineered behaviors and scalability of the engineered systems. Here, we present a platform technology, microbial swarmbot, which employs spatial arrangement to control the growth dynamics of engineered bacteria. As a proof of principle, we demonstrated a safeguard strategy to prevent unintended bacterial proliferation. In particular, we adopted several synthetic gene circuits to program collective survival in Escherichia coli: the engineered bacteria could only survive when present at sufficiently high population densities. When encapsulated by permeable membranes, these bacteria can sense the local environment and respond accordingly. The cells inside the microbial swarmbot capsules will survive due to their high densities. Those escaping from a capsule, however, will be killed due to a decrease in their densities. We demonstrate that this design concept is modular and readily generalizable. Our work lays the foundation for engineering integrated and programmable control of hybrid biological-material systems for diverse applications.

Competitive Swarm Optimizer Based Gateway Deployment Algorithm in Cyber-Physical Systems.

Wireless sensor network topology optimization is a highly important issue, and topology control through node selection can improve the efficiency of data forwarding, while saving energy and prolonging lifetime of the network. To address the problem of connecting a wireless sensor network to the Internet in cyber-physical systems, here we propose a geometric gateway deployment based on a competitive swarm optimizer algorithm. The particle swarm optimization (PSO) algorithm has a continuous search feature in the solution space, which makes it suitable for finding the geometric center of gateway deployment; however, its search mechanism is limited to the individual optimum (pbest) and the population optimum (gbest); thus, it easily falls into local optima. In order to improve the particle search mechanism and enhance the search efficiency of the algorithm, we introduce a new competitive swarm optimizer (CSO) algorithm. The CSO search algorithm is based on an inter-particle competition mechanism and can effectively avoid trapping of the population falling into a local optimum. With the improvement of an adaptive opposition-based search and its ability to dynamically parameter adjustments, this algorithm can maintain the diversity of the entire swarm to solve geometric K-center gateway deployment problems. The simulation results show that this CSO algorithm has a good global explorative ability as well as convergence speed and can improve the network quality of service (QoS) level of cyber-physical systems by obtaining a minimum network coverage radius. We also find that the CSO algorithm is more stable, robust and effective in solving the problem of geometric gateway deployment as compared to the PSO or Kmedoids algorithms.

The association between wet overactive bladder and consumption of tea, coffee, and caffeine: Results from 2005-2018 National Health and Nutrition Examination Survey.

BACKGROUND & AIMS: Previous studies have reported an inconsistent relationship between overactive bladder (OAB) and the consumption of tea, coffee, and caffeine. Our study aims to determine these associations in a large and nationally representative adult sample. METHODS: This cross-sectional study included 15,379 participants from the 2005-2018 US National Health and Nutrition Examination Survey (NHANES) database. The outcome was the risk of wet OAB that was diagnosed when the OAB symptom score was ≥3 with urgent urinary incontinence and excluded other diseases affecting diagnosis. The exposures were the consumption of tea, coffee, and caffeine. Weighted logistic regression models were established to explore these associations by calculating odds ratios (OR) and 95% confidence intervals (CI), as did restricted cubic splines (RCS) used to analyze the nonlinear associations. RESULT: Of all the participants (n = 15,379), 2207 had wet OAB. Mean [SE] consumption of tea, total coffee, caffeinated coffee, decaffeinated coffee, and caffeine was 233.6 [15.7] g/day, 364.3 [15.5] g/day, 301.6 [14.9] g/day, 62.7 [7.9] g/day, 175.5 [6.6] mg/day in participants with wet OAB, respectively. In the fully adjusted model, compared to those without tea consumption, the high consumption of tea (>481 g/day) was associated with an increased risk of wet OAB (OR: 1.29; 95%CI: 1.01-1.64). Low decaffeinated coffee (0.001-177.6 g/day) had a negative association with the risk (OR: 0.66; 95%CI: 0.49-0.90). In the RCS analysis, tea consumption showed a positive linear association with the risk of wet OAB, and decaffeinated coffee showed a nonlinear relationship with the risk and had a turning point of 78 g/day in the U-shaped curve between 0 and 285 g/day. Besides, total coffee, caffeinated coffee, and caffeine consumption had no significant association with the risk. Interestingly, in the high tea consumption, participants with high total coffee consumption [>527.35 g/day, OR and 95%CI: 2.14(1.16-3.94)] and low caffeine consumption [0.1-74.0 mg/day, OR and 95%CI: 1.50(1.03-2.17)] were positively associated with the risk of wet OAB. CONCLUSION: High tea consumption was associated with the increased risk of wet OAB, especially intake together with high total coffee and low caffeine consumption, but no significant association with the single consumption of total coffee and caffeine. Low decaffeinated coffee was associated with a decreased risk of wet OAB. It is necessary to control tea intake when managing the liquid intake of wet OAB patients.

Microscale Searching Algorithm for Coupling Matrix Optimization of Automated Microwave Filter Tuning.

Automated tuning can significantly improve productivity and save the costs of manual operation in the microwave filter manufacturing industry. This article proposes a mathematical model of scattering data optimization to find the accurate coupling matrix for multiple-version microwave filters, a core step of automated microwave filter tuning. For the large-scale problem of coupling coefficient combination, we propose a decision set decomposition strategy that evenly divides the entire frequency interval into several subintervals according to the correlation between scattering data. With this strategy, we design a microscale (small-size subsets of the decomposed decision set) searching algorithm, which solves each suboptimization problem by searching the decision subset instead of the entire decision set. To verify the validity of the proposed algorithm for multiple-version microwave filters, experiments are conducted on three versions of microwave filters from a real-world production line, including the two-port eighth-order, ninth-order, and tenth-order microwave filters. Experimental results show that the proposed model is feasible within the industrial error for the multiversion microwave filter tuning problem. Besides, the proposed algorithm outperforms the state-of-the-art optimization algorithms in the coupling matrix optimization problem.

Extracellular Vesicles in Cardiovascular Diseases: Diagnosis and Therapy.

Cardiovascular diseases (CVDs) are the leading cause of global mortality. Therapy of CVDs is still a great challenge since many advanced therapies have been developed. Multiple cell types produce nano-sized extracellular vesicles (EVs), including cardiovascular system-related cells and stem cells. Compelling evidence reveals that EVs are associated with the pathophysiological processes of CVDs. Recently researches focus on the clinical transformation in EVs-based diagnosis, prognosis, therapies, and drug delivery systems. In this review, we firstly discuss the current knowledge about the biophysical properties and biological components of EVs. Secondly, we will focus on the functions of EVs on CVDs, and outline the latest advances of EVs as prognostic and diagnostic biomarkers, and therapeutic agents. Finally, we will introduce the specific application of EVs as a novel drug delivery system and its application in CVDs therapy. Specific attention will be paid to summarize the perspectives, challenges, and applications on EVs' clinical and industrial transformation.

Corrigendum: Emerging microfluidic technologies for microbiome research.

[This corrects the article DOI: 10.3389/fmicb.2022.906979.].

Emerging microfluidic technologies for microbiome research.

The importance of the microbiome is increasingly prominent. For example, the human microbiome has been proven to be strongly associated with health conditions, while the environmental microbiome is recognized to have a profound influence on agriculture and even the global climate. Furthermore, the microbiome can serve as a fascinating reservoir of genes that encode tremendously valuable compounds for industrial and medical applications. In the past decades, various technologies have been developed to better understand and exploit the microbiome. In particular, microfluidics has demonstrated its strength and prominence in the microbiome research. By taking advantage of microfluidic technologies, inherited shortcomings of traditional methods such as low throughput, labor-consuming, and high-cost are being compensated or bypassed. In this review, we will summarize a broad spectrum of microfluidic technologies that have addressed various needs in the field of microbiome research, as well as the achievements that were enabled by the microfluidics (or technological advances). Finally, how microfluidics overcomes the limitations of conventional methods by technology integration will also be discussed.

Microfluidic synthesis of tunable poly-(N-isopropylacrylamide) microparticles via PEG adjustment.

We present a microfluidic droplet method to synthesize a series of tunable poly(N-isopropylacrylamide) (PNIPAM) microparticles by the addition of polyethylene glycols (PEGs). The PEGs are used as porogens and could be removed simply by washing step. By varying molecular weights and concentrations of the PEGs, morphologies and temperature-sensitive properties of the formed PNIPAM microparticles are flexibly tuned. It is found that PEG of lower molecular weight induces smaller micropore sizes, and results in faster response rate. The volume changes prior to and after shrinkage can also be regulated by the addition of PEGs due to tuned homogeneities of micropores. The microparticles tuned by PEG1000 with ratio of added PEGs to NIPAM of 2:1 respond the fastest (120 s), whereas with ratio of added PEGs to NIPAM of 1:1 display largest volume change (1/γ=12.12). This simplicity and controllability of tunable microparticles synthesis are appealing for various applications ranging from chemical delivery, drug release control, to optical applications.

Engineering Gac/Rsm Signaling Cascade for Optogenetic Induction of the Pathogenicity Switch in Pseudomonas aeruginosa.

Bacterial pathogens operate by tightly controlling the pathogenicity to facilitate invasion and survival in host. While small molecule inducers can be designed to modulate pathogenicity to perform studies of pathogen-host interaction, these approaches, due to the diffusion property of chemicals, may have unintended, or pleiotropic effects that can impose limitations on their use. By contrast, light provides superior spatial and temporal resolution. Here, using optogenetics we reengineered GacS of the opportunistic pathogen Pseudomonas aeruginosa, signal transduction protein of the global regulatory Gac/Rsm cascade which is of central importance for the regulation of infection factors. The resultant protein (termed YGS24) displayed significant light-dependent activity of GacS kinases in Pseudomonas aeruginosa. When introduced in the Caenorhabditis elegans host systems, YGS24 stimulated the pathogenicity of the Pseudomonas aeruginosa strain PAO1 in a brain-heart infusion and of another strain, PA14, in slow killing media progressively upon blue-light exposure. This optogenetic system provides an accessible way to spatiotemporally control bacterial pathogenicity in defined hosts, even specific tissues, to develop new pathogenesis systems, which may in turn expedite development of innovative therapeutics.

Microvalve and micropump controlled shuttle flow microfluidic device for rapid DNA hybridization.

We present a novel microfluidic device integrated with microvalves and micropumps for rapid DNA hybridization using shuttle flow. The device is composed of 48 hybridization units containing 48 microvalves and 96 micropumps for the automation of shuttle flow. We used four serotypes of Dengue Virus genes (18mer) to demonstrate that the automatic shuttle flow shortened the hybridization time to 90 s, reduced sample consumption to 1 µL and lowered detection limit to 100 pM (100 amol in a 1 µL sample). Moreover, we applied this device to realize single base discrimination and analyze 48 samples containing different DNA targets, simultaneously. For kinetic measurements of nucleotide hybridization, on-line monitoring of the processes was carried out. This rapid hybridization device has the ability for accommodating the entire hybridization process (i.e., injection, hybridization, washing, detection, signal acquisition) in an automated and high-throughput fashion.

Gut-on-chip: Recreating human intestine in vitro.

The human gut is important for food digestion and absorption, as well as a venue for a large number of microorganisms that coexist with the host. Although numerous in vitro models have been proposed to study intestinal pathology or interactions between intestinal microbes and host, they are far from recapitulating the real intestinal microenvironment in vivo. To assist researchers in further understanding gut physiology, the intestinal microbiome, and disease processes, a novel technology primarily based on microfluidics and cell biology, called "gut-on-chip," was developed to simulate the structure, function, and microenvironment of the human gut. In this review, we first introduce various types of gut-on-chip systems, then highlight their applications in drug pharmacokinetics, host-gut microbiota crosstalk, and nutrition metabolism. Finally, we discuss challenges in this field and prospects for better understanding interactions between intestinal flora and human hosts, and then provide guidance for clinical treatment of related diseases.

Oral delivery of bacteria: Basic principles and biomedical applications.

Bacterial therapy, which presents a smart platform for delivering and producing therapeutic agents, as monotherapy or in combination with other therapeutic modes, has provided a breakthrough for the treatment of a range of diseases. The integration of synthetic biology technology with bacteria enables their characteristics like chemotaxis and biomolecule secretion to outperform conventional diagnostics and therapeutics, thereby facilitating their clinical applications in a range of diseases. Compared to injection-administered bacteria, orally-delivered bacteria improve patient compliance while avoiding the risk of systemic infections. However, oral administration of microbes always leads to a substantial loss of viability due to the highly acidic environment in the stomach and bile salt in the intestine. Thus, the formulation of these bacteria into microcapsules using appropriate biomaterials is a promising approach for reducing cell death during gastrointestinal passage and controlling the release of these therapeutic cells across the intestinal tract. In this review, we reveal the basic principles of oral bacterial delivery, from internal genetic engineering approaches to external encapsulation and modification, and summarize the most recent biomedical applications. Finally, we discuss future trends in oral bacterial therapy as well as current challenges that need to be resolved to advance their clinical applications.

Interindividual Variation in Dietary Carbohydrate Metabolism by Gut Bacteria Revealed with Droplet Microfluidic Culture.

Culture and screening of gut bacteria enable testing of microbial function and therapeutic potential. However, the diversity of human gut microbial communities (microbiota) impedes comprehensive experimental studies of individual bacterial taxa. Here, we combine advances in droplet microfluidics and high-throughput DNA sequencing to develop a platform for separating and assaying growth of microbiota members in picoliter droplets (MicDrop). MicDrop enabled us to cultivate 2.8 times more bacterial taxa than typical batch culture methods. We then used MicDrop to test whether individuals possess similar abundances of carbohydrate-degrading gut bacteria, using an approach which had previously not been possible due to throughput limitations of traditional bacterial culture techniques. Single MicDrop experiments allowed us to characterize carbohydrate utilization among dozens of gut bacterial taxa from distinct human stool samples. Our aggregate data across nine healthy stool donors revealed that all of the individuals harbored gut bacterial species capable of degrading common dietary polysaccharides. However, the levels of richness and abundance of polysaccharide-degrading species relative to monosaccharide-consuming taxa differed by up to 2.6-fold and 24.7-fold, respectively. Additionally, our unique dataset suggested that gut bacterial taxa may be broadly categorized by whether they can grow on single or multiple polysaccharides, and we found that this lifestyle trait is correlated with how broadly bacterial taxa can be found across individuals. This demonstration shows that it is feasible to measure the function of hundreds of bacterial taxa across multiple fecal samples from different people, which should in turn enable future efforts to design microbiota-directed therapies and yield new insights into microbiota ecology and evolution.IMPORTANCE Bacterial culture and assay are components of basic microbiological research, drug development, and diagnostic screening. However, community diversity can make it challenging to comprehensively perform experiments involving individual microbiota members. Here, we present a new microfluidic culture platform that makes it feasible to measure the growth and function of microbiota constituents in a single set of experiments. As a proof of concept, we demonstrate how the platform can be used to measure how hundreds of gut bacterial taxa drawn from different people metabolize dietary carbohydrates. Going forward, we expect this microfluidic technique to be adaptable to a range of other microbial assay needs.