Search

Abstract Microelectronic devices can directly communicate with biology, as electronic information can be transmitted via redox reactions within biological systems. By engineering biology’s native redox networks, we enable electronic interrogation and control of biological systems at several hierarchical levels: proteins, cells, and cell consortia. First, electro-biofabrication facilitates on-device biological component assembly. Then, electrode-actuated redox data transmission and redox-linked synthetic biology allows programming of enzyme activity and closed-loop electrogenetic control of cellular function. Specifically, horseradish peroxidase is assembled onto interdigitated electrodes where electrode-generated hydrogen peroxide controls its activity. E. coli’s stress response regulon, oxyRS, is rewired to enable algorithm-based feedback control of gene expression, including an eCRISPR module that switches cell-cell quorum sensing communication from one autoinducer to another—creating an electronically controlled ‘bilingual’ cell. Then, these disparate redox-guided devices are wirelessly connected, enabling real-time communication and user-based control. We suggest these methodologies will help us to better understand and develop sophisticated control for biology.

Objectives The incidence of waterborne and foodborne infectious diseases (WFIDs) continues to increase annually, attracting significant global attention. This study examined trends in WFID outbreaks in the Republic of Korea over the 5-year period before and during the coronavirus disease 2019 (COVID-19) pandemic and provided foundational data to establish measures for the prevention and control of WFID outbreaks. Methods We analyzed 2,541 WFID outbreaks from 2017 to 2021 (42,805 cases) that were reported through the Integrated Disease Surveillance System of the Korea Disease Control and Prevention Agency. Outbreaks were defined as the occurrence of gastrointestinal symptoms in ≥2 individuals within a group with temporal and regional epidemiological associations. The related factors associated with WFID outbreaks during the observation period were statistically analyzed. Results The total number of WFID outbreaks significantly decreased in 2020 during the COVID-19 pandemic and increased to the pre-pandemic level in 2021. Different patterns were observed for each pathogen. The incidence of Salmonella outbreaks more than doubled, while norovirus outbreaks decreased significantly. Conclusion WFID outbreaks in the Republic of Korea showed different patterns before and during the COVID-19 pandemic, influenced by infection control measures and changes in dietary consumption patterns. Outbreaks of some diseases increased, but the infection control measures applied during the pandemic resulted in a significant decrease in the overall number of WFID outbreaks. This highlights the importance of strengthening the management strategies for outbreak prevention through hygiene inspections, long-term monitoring, education, and promotion by conducting multidimensional analyses to understand the complex related factors.

Abstract Background The COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool was developed to assist countries to estimate incremental financial costs to roll out COVID-19 vaccines. This article describes the purposes, assumptions and methods used in the CVIC tool and presents the estimated financial costs of delivering COVID-19 vaccines in the Lao People’s Democratic Republic (Lao PDR). Methods From March to September 2021, a multidisciplinary team in Lao PDR was involved in the costing exercise of the National Deployment and Vaccination Plan for COVID-19 vaccines to develop potential scenarios and gather inputs using the CVIC tool. Financial costs of introducing COVID-19 vaccines for 3 years from 2021 to 2023 were projected from the government perspective. All costs were collected in 2021 Lao Kip and presented in United States dollar. Results From 2021 to 2023, the financial cost required to vaccinate all adults in Lao PDR with primary series of COVID-19 vaccines (1 dose for Ad26.COV2.S (recombinant) vaccine and 2 doses for the other vaccine products) is estimated to be US$6.44 million (excluding vaccine costs) and additionally US$1.44 million and US$1.62 million to include teenagers and children, respectively. These translate to financial costs of US$0.79–0.81 per dose, which decrease to US$0.6 when two boosters are introduced to the population. Capital and operational cold-chain costs contributed 15–34% and 15–24% of the total costs in all scenarios, respectively. 17–26% went to data management, monitoring and evaluation, and oversight, and 13–22% to vaccine delivery. Conclusions With the CVIC tool, costs of five scenarios were estimated with different target population and booster dose use. These facilitated Lao PDR to refine their strategic planning for COVID-19 vaccine rollout and to decide on the level of external resources needed to mobilize and support outreach services. The results may further inform inputs in cost-effectiveness or cost–benefit analyses and potentially be applied and adjusted in similar low- and middle-income settings.

The toxicity of paraquat is believed to involve a redox-cycling mechanism that can disrupt cellular redox homeostasis and, also, generate damaging free radicals. It has been suggested that for cases of severe paraquat poisoning the administration of ascorbate (i.e., vitamin C) can confer benefit by quenching the paraquat free radical (PQ+·). Here, we used an electrochemical approach that abstracts-away many of the (bio)chemical complexities and isolates the redox-interactions between paraquat and ascorbate. Specifically, we used a series of experiments that coupled electrochemical measurements of electron flow with optical measurements of paraquat's redox-state switching. Our results demonstrate that the reduced absorbate cannot quench the PQ+·-radical because they are both reductants. However, oxidation of ascorbate does allow PQ+·-radical scavenging. More broadly, we believe this study demonstrates the potential for developing electrochemical approaches to complement existing experimental methods in redox biology.

OBJECTIVES As few mpox cases have been reported in Korea, we aimed to identify the characteristics of mpox infection by describing our epidemiologic investigation of a woman patient (index patient, the third case in Korea) and a physician who was infected by a needlestick injury (the fourth case). METHODS We conducted contact tracing and exposure risk evaluation through interviews with these 2 patients and their physicians and contacts, as well as field investigations at each facility visited by the patients during their symptomatic periods. We then classified contacts into 3 levels according to their exposure risk and managed them to minimize further transmission by recommending quarantine and vaccination for post-exposure prophylaxis and monitoring their symptoms. RESULTS The index patient had sexual contact with a man foreigner during a trip to Dubai, which was considered the probable route of transmission. In total, 27 healthcare-associated contacts across 7 healthcare facilities and 9 community contacts were identified. These contacts were classified into high (7 contacts), medium (9 contacts), and low (20 contacts) exposure risk groups. One high-risk contact was identified as a secondary patient: a physician who was injured while collecting specimens from the index patient. CONCLUSIONS The index patient visited several medical facilities due to progressive symptoms prior to isolation. Although the 2022 mpox epidemic mainly affected young men, especially men who have sex with men, physicians should also consider mpox transmission in the general population for the timely detection of mpox-infected patients.

Understanding the underlying spin- and photo-physics of ultralong-lived light emission in organic materials remains a significant challenge. Here, the authors report spin-orbital coupling and slow phonon effects in light-emitting organic molecules and elucidate their underlying physics.

Summary: Recent observations that abiotic materials can engage in redox-based interactive communication motivates the search for new redox-active materials. Here we fabricated a hydrogel from a four-armed thiolated polyethylene glycol (PEG-SH) and the bacterial metabolite, pyocyanin (PYO). We show that: (i) the PYO-PEG hydrogel is reversibly redox-active; (ii) the molecular-switching and directed electron flow within this PYO-PEG hydrogel requires both a thermodynamic driving force (i.e., potential difference) and diffusible electron carriers that serve as nodes in a redox network; (iii) this redox-switching and electron flow is controlled by the redox network’s topology; and (iv) the ability of the PYO-PEG hydrogel to “transmit” electrons to a second insoluble redox-active material (i.e., a catechol-PEG hydrogel) is context-dependent (i.e., dependent on thermodynamic driving forces and appropriate redox shuttles). These studies provide an experimental demonstration of important features of redox-communication and also suggest technological opportunities for the fabrication of interactive materials.

Growing evidence implicates an association between psychosocial stress and oxidative stress (OxSt) although there are not yet reliable biomarkers to study this association. We used a Trier Social Stress Test (TSST) and compared the response of a healthy control group (HC; N=10) against the response of a schizophrenia group (SCZ; N=10) that is expected to have higher levels of OxSt. Because our previous study showed inconsistent changes in conventional molecular markers for stress responses in the neuroendocrine and immune systems, we analyzed the same serum samples using a separate reducing capacity assay that provides a more global measurement of OxSt. This assay uses the moderately strong oxidizing agent iridium (Ir) to probe a sample's reducing capacity. Specifically, we characterized OxSt by this Ir-reducing capacity assay (Ir-RCA) using two measurement modalities (optical and electrochemical) and we tuned this assay by imposing an input voltage sequence that generates multiple output metrics for data-driven analysis. We defined five OxSt metrics (one optical and four electrochemical metrics) and showed: (i) internal consistency among each metric in the measurements of all 40 samples (baseline and post TSST for N=20); (ii) all five metrics were consistent with expectations of higher levels of OxSt for the SCZ group (three individual metrics showed statistically significant differences); and (iii) all five metrics showed higher levels of OxSt Post-TSST (one metric showed statistically significant difference). Using multivariant analysis, we showed that combinations of OxSt metrics could discern statistically significant increases in OxSt for both the SCZ and HC groups 90 min after the imposed acute psychosocial stress.

Summary: The ubiquitin-proteasome system and the autophagy-lysosome system are two major intracellular proteolytic pathways in eukaryotes. Although several biochemical mechanisms underlying the crosstalk between them have been suggested, little is known about the effect of enhanced proteasome activity on autophagic flux. Here, we found that upregulation of proteasome activity, which was achieved through the inhibition of USP14, significantly impaired cellular autophagic flux, especially at the autophagosome-lysosome fusion step. UVRAG appeared to function as a crucial checkpoint for the proper progression of autophagic flux. Although proteasome activation through USP14 inhibition facilitated the clearance of microtubule-associated protein tau (MAPT) and reduced the amount of its oligomeric forms, the same conditions increased the formation of inclusion bodies from nonproteasomal substrates such as huntingtin with long polyglutamine repeats. Our results collectively indicate that USP14 may function as a common denominator in the compensatory negative feedback between the two major proteolytic processes in the cell. : Kim et al. present evidence that the ubiquitin-proteasome system and autophagy are in a compensatory negative-feedback connection through USP14, a proteasome-associated deubiquitinating enzyme. USP14 inhibition results in elevation of proteasome activity and facilitation of tau degradation in the cell, while it delays the cellular autophagic flux. Keywords: USP14, proteasome, ubiquitin-proteasome system, autophagy, autophagic flux, negative feedback, UVRAG, proteostasis, tau, huntingtin

Cellular stress induces the formation of membraneless protein condensates in both the nucleus and cytoplasm. The nucleocytoplasmic transport of proteins mainly occurs through nuclear pore complexes (NPCs), whose efficiency is affected by various stress conditions. Here, we report that hyperosmotic stress compartmentalizes nuclear 26S proteasomes into dense nuclear foci, independent of signaling cascades. Most of the proteasome foci were detected between the condensed chromatin mass and inner nuclear membrane. The proteasome-positive puncta were not colocalized with other types of nuclear bodies and were reversibly dispersed when cells were returned to the isotonic medium. The structural integrity of 26S proteasomes in the nucleus was slightly affected under the hyperosmotic condition. We also found that these insulator-body-like proteasome foci were possibly formed through disrupted nucleus-to-cytosol transport, which was mediated by the sequestration of NPC components into osmostress-responding stress granules. These data suggest that phase separation in both the nucleus and cytosol may be a major cell survival mechanism during hyperosmotic stress conditions.

Synthetic biology offers the ability to explore new ways of manipulating gene expression and function. Here the authors demonstrate an electrogenetic device that allows control of transcription by an exogenous electrical signal.

Catechols are abundant in nature and are believed to perform diverse biological functions that include photoprotection (e.g., melanins), molecular signaling (e.g., catecholamine neurotransmitters), and mechanical adhesion (e.g., mussel glue). Currently, the structure-property-function relationships for catechols remain poorly resolved, and this is especially true for redox-based properties (e.g., antioxidant, pro-oxidant, and radical scavenging activities). Importantly, there are few characterization methods available to probe the redox properties of materials. In this review, we focus on recent studies with redox-active catechol-chitosan films. First, we describe film fabrication methods to oxidatively-graft catechols to chitosan through chemical, enzymatic, or electrochemical methods. Second, we discuss a new experimental characterization method to probe the redox properties of catechol-functionalized materials. This mediated electrochemical probing (MEP) method probes the redox-activities of catechol-chitosan films by: (i) employing diffusible mediators to shuttle electrons between the electrode and grafted catechols; (ii) imposing tailored sequences of input voltages to “tune” redox probing; and (iii) analyzing the output current response characteristics to infer properties. Finally, we demonstrate that the redox properties of catechol-chitosan films enable them to perform antioxidant radical scavenging functions, as well as a pro-oxidant (reactive oxygen-generation) antimicrobial functions. In summary, our increasing knowledge of catechol-chitosan films is enabling us to better-understand the functions of catechols in biology as well as enhancing our capabilities to create advanced functional materials.

Individually, advances in microelectronics and biology transformed the way we live our lives. However, there remain few examples in which biology and electronics have been interfaced to create synergistic capabilities. We believe there are two major challenges to the integration of biological components into microelectronic systems: (i) assembly of the biological components at an electrode address, and (ii) communication between the assembled biological components and the underlying electrode. Chitosan possesses a unique combination of properties to meet these challenges and serve as an effective bio-device interface material. For assembly, chitosan’s pH-responsive film-forming properties allow it to “recognize” electrode-imposed signals and respond by self-assembling as a stable hydrogel film through a cathodic electrodeposition mechanism. A separate anodic electrodeposition mechanism was recently reported and this also allows chitosan hydrogel films to be assembled at an electrode address. Protein-based biofunctionality can be conferred to electrodeposited films through a variety of physical, chemical and biological methods. For communication, we are investigating redox-active catechol-modified chitosan films as an interface to bridge redox-based communication between biology and an electrode. Despite significant progress over the last decade, many questions still remain which warrants even deeper study of chitosan’s structure, properties, and functions.

A roll-type conducting polymer film was explored as a flexible organic p-type thermoelectric leg using poly(3,4-ethylenedioxythiophene) (PEDOT) doped with tosylate. The PEDOT films were prepared through solution casting polymerization and rolled up for a roll-type leg. Due to the high flexibility, the roll-type PEDOT leg enabled easy contact to both top and bottom electrodes. Simulation on the dynamic heat transfer and convective cooling for a vertically roosted rod- and roll-type PEDOT leg showed that the temperature difference (ΔT) between the hot and cold sides of the leg was much higher in the roll than that of the rod. The PEDOT legs were integrated with n-type Bi2Te3 blocks, to give a 36-couple rigid-flexible thermoelectric generator (RF-TEG). The maximum output voltage from the 36-couple RF-TEG under a ΔT of 7.9 K was determined as 36.7 mV along with a high output power of 115 nW. A wearable RF-TEG was prepared upon the combination of the 36-couple RF-TEG with an arm warmer, to afford an output voltage of 10.6 mV, which was generated constantly and steadily from human wrist heat.

n/a

When measuring chemical information in biological fluids, challenges of cross-reactivity arise, especially in sensing applications where no biological recognition elements exist. An understanding of the cross-reactions involved in these complex matrices is necessary to guide the design of appropriate sensing systems. This work presents a methodology for investigating cross-reactions in complex fluids. First, a systematic screening of matrix components is demonstrated in buffer-based solutions. Second, to account for the effect of the simultaneous presence of these species in complex samples, the responses of buffer-based simulated mixtures of these species were characterized using an arrayed sensing system. We demonstrate that the sensor array, consisting of electrochemical sensors with varying input parameters, generated differential responses that provide synergistic information of sample. By mapping the sensing array response onto multidimensional heat maps, characteristic signatures were compared across sensors in the array and across different matrices. Lastly, the arrayed sensing system was applied to complex biological samples to discern and match characteristic signatures between the simulated mixtures and the complex sample responses. As an example, this methodology was applied to screen interfering species relevant to the application of schizophrenia management. Specifically, blood serum measurement of antipsychotic clozapine and antioxidant species can provide useful information regarding therapeutic efficacy and psychiatric symptoms. This work proposes an investigational tool that can guide multi-analyte sensor design, chemometric modeling and biomarker discovery.

Clozapine (CLZ), a dibenzodiazepine, is demonstrated as the optimal antipsychotic for patients suffering from treatment-resistant schizophrenia. Like many other drugs, understanding the concentration of CLZ in a patient’s blood is critical for managing the patients’ symptoms, side effects, and overall treatment efficacy. To that end, various electrochemical techniques have been adapted due to their capabilities in concentration-dependent sensing. An open question associated with electrochemical CLZ monitoring is whether drug–protein complexes (i.e., CLZ bound to native blood proteins, such as serum albumin (SA) or alpha-1 acid-glycoprotein (AAG)) contribute to electrochemical redox signals. Here, we investigate CLZ-sensing performance using fundamental electrochemical methods with respect to the impact of protein binding. Specifically, we test the activity of bound and free fractions of a mixture of CLZ and either bovine SA or human AAG. Results suggest that bound complexes do not significantly contribute to the electrochemical signal for mixtures of CLZ with AAG or SA. Moreover, the fraction of CLZ bound to protein is relatively constant at 31% (AAG) and 73% (SA) in isolation with varying concentrations of CLZ. Thus, electrochemical sensing can enable direct monitoring of only the unbound CLZ, previously only accessible via equilibrium dialysis. The methods utilized in this work offer potential as a blueprint in developing electrochemical sensors for application to other redox-active medications with high protein binding more generally. This demonstrates that electrochemical sensing can be a new tool in accessing information not easily available previously, useful toward optimizing treatment regimens.

Catechols offer diverse properties and are used in biology to perform various functions that range from adhesion (e.g., mussel proteins) to neurotransmission (e.g., dopamine), and mimicking the capabilities of biological catechols have yielded important new materials (e.g., polydopamine). It is well known that catechols are also redox-active and we have observed that biomimetic catechol-modified chitosan films are redox-active and possess interesting molecular electronic properties. In particular, these films can accept, store and donate electrons, and thus offer redox-capacitor capabilities. We are enlisting these capabilities to bridge communication between biology and electronics. Specifically, we are investigating an interactive redox-probing approach to access redox-based chemical information and convert this information into an electrical modality that facilitates analysis by methods from signal processing. In this review, we describe the broad vision and then cite recent examples in which the catechol–chitosan redox-capacitor can assist in accessing and understanding chemical information. Further, this redox-capacitor can be coupled with synthetic biology to enhance the power of chemical information processing. Potentially, the progress with this biomimetic catechol–chitosan film may even help in understanding how biology uses the redox properties of catechols for redox signaling.