A gray box framework that optimizes a white box logical model using a black box optimizer for simulating cellular responses to perturbations.

Predicting cellular responses to perturbations requires interpretable insights into molecular regulatory dynamics to perform reliable cell fate control, despite the confounding non-linearity of the underlying interactions. There is a growing interest in developing machine learning-based perturbation response prediction models to handle the non-linearity of perturbation data, but their interpretation in terms of molecular regulatory dynamics remains a challenge. Alternatively, for meaningful biological interpretation, logical network models such as Boolean networks are widely used in systems biology to represent intracellular molecular regulation. However, determining the appropriate regulatory logic of large-scale networks remains an obstacle due to the high-dimensional and discontinuous search space. To tackle these challenges, we present a scalable derivative-free optimizer trained by meta-reinforcement learning for Boolean network models. The logical network model optimized by the trained optimizer successfully predicts anti-cancer drug responses of cancer cell lines, while simultaneously providing insight into their underlying molecular regulatory mechanisms.

Decoding the principle of cell-fate determination for its reverse control.

Understanding and manipulating cell fate determination is pivotal in biology. Cell fate is determined by intricate and nonlinear interactions among molecules, making mathematical model-based quantitative analysis indispensable for its elucidation. Nevertheless, obtaining the essential dynamic experimental data for model development has been a significant obstacle. However, recent advancements in large-scale omics data technology are providing the necessary foundation for developing such models. Based on accumulated experimental evidence, we can postulate that cell fate is governed by a limited number of core regulatory circuits. Following this concept, we present a conceptual control framework that leverages single-cell RNA-seq data for dynamic molecular regulatory network modeling, aiming to identify and manipulate core regulatory circuits and their master regulators to drive desired cellular state transitions. We illustrate the proposed framework by applying it to the reversion of lung cancer cell states, although it is more broadly applicable to understanding and controlling a wide range of cell-fate determination processes.

A Review of Rechargeable Zinc-Air Batteries: Recent Progress and Future Perspectives.

Zinc-air batteries (ZABs) are gaining attention as an ideal option for various applications requiring high-capacity batteries, such as portable electronics, electric vehicles, and renewable energy storage. ZABs offer advantages such as low environmental impact, enhanced safety compared to Li-ion batteries, and cost-effectiveness due to the abundance of zinc. However, early research faced challenges due to parasitic reactions at the zinc anode and slow oxygen redox kinetics. Recent advancements in restructuring the anode, utilizing alternative electrolytes, and developing bifunctional oxygen catalysts have significantly improved ZABs. Scientists have achieved battery reversibility over thousands of cycles, introduced new electrolytes, and achieved energy efficiency records surpassing 70%. Despite these achievements, there are challenges related to lower power density, shorter lifespan, and air electrode corrosion leading to performance degradation. This review paper discusses different battery configurations, and reaction mechanisms for electrically and mechanically rechargeable ZABs, and proposes remedies to enhance overall battery performance. The paper also explores recent advancements, applications, and the future prospects of electrically/mechanically rechargeable ZABs.

Development of fluorescent GO-AgNPs-Eu3+ nanoparticles based paper visual sensor for foodborne spores detection.

Foodborne spores are ubiquitous with extremely strong resistance, and pose a serious threat to food safety and human health. Therefore, rapid, sensitive, and selective detection of spores are crucial. In this study, a fluorescent probe was developed based on lanthanide ion (Eu3+)-labeled nano-silver-modified graphene oxide (GO-AgNPs-Eu3+) for the detection of 2,6-dipicolinic acid (DPA), a biomarker unique to spores, to allow quantitative spores detection. The GO-AgNPs-Eu3+ nano-fluorescent probe was loaded onto a polyvinylidene fluoride microfiltration membrane, and a smartphone-assisted portable GO-AgNPs-Eu3+ nanoparticles-based paper visual sensor was designed for rapid on-site quantitative and real-time online detection of spores. The results indicated that the developed probe achieved equilibrium binding with DPA within 5 min, and enhanced fluorescence emission through antenna effect. The fluorescence detection presented a good linear relationship in the DPA concentration range of 0-45 µM, with a DPA detection limit of 4.62 nM and spore detection limit of 104 cfu/mL. The developed sensor showed a change in fluorescence from blue to red with increasing DPA concentration, and this color change was quantitatively detected through smartphone RGB variations, with a detection limit of 13.1 µM for DPA and 6.3 cfu/mL for Bacillus subtilis spores. Subsequently, the sensitivity and selectivity of the developed sensor were verified using actual milk and water samples spiked with B. subtilis spores. The results of this study provided objective technological support for rapid detection of spores, which is important for reducing the occurrence of foodborne diseases and improving food safety.

Selective purification and rapid quantitative detection of spores using a "stepped" magnetic flow device.

A study on the inactivation and germination mechanism of spores is very important in the application of spores, as such high-purity spores are the basis of related research. However, spores and vegetative cells of bacteria often coexist, and it is difficult to separate them. In this study, a magnetic flow device for the purification of spores in the culture medium system was developed based on a "stepped" structure with a magnetic force that could absorb vegetative cells with magnetic nanoparticles. The operation process was as follows: first, vancomycin functionalized nanoparticles were used to prepare Van-Fe3O4 NPs, which were then combined with vegetative cells to form a magnetic conjugate. Subsequently, the magnetic conjugate (vegetative cells) flowed through the "stepped" magnetic flow device and was adsorbed. Meanwhile, the spores moved through the channel and were collected. The achieved purity of the collected spores was more than 95%. Further, the number of the obtained spores was quickly quantified using Raman spectroscopy. The entire purification and quantitative process can be completed within 30 min and the limit of detection was 5 CFU mL-1. This study showed outstanding spore purification ability and provided a new method for purification and rapid quantitative detection of spores.

Incidence of intraoperative hypotension in older patients undergoing total intravenous anesthesia by remimazolam versus propofol: A randomized controlled trial.

BACKGROUND: An increase in the frequency of surgeries among older individuals is observed in some countries. Hypotension is common and exaggerated in older patients and can lead to increased morbidity and mortality. Total intravenous anesthesia is commonly administered with propofol, while remimazolam has been suggested as an alternative to propofol because of advantages such as a more stable hemodynamic profile and less respiratory suppression. We conducted a single-blind, parallel-group randomized controlled trial to compare the incidence of intraoperative hypotension between patients administered with remimazolam and propofol. METHODS: A total of 132 patients, aged between 65 to 80 years and undergoing laparoscopic cholecystectomy or transurethral resection of bladder tumors were randomly assigned to the propofol or remimazolam group with a permuted block system while being blinded to the hypnotic agent. Remifentanil was administered via target-controlled infusion in both groups, with an initial effect-site concentration of 3.0 ng/mL and titration range of 1.5 to 4.0 ng/mL intraoperatively. The primary outcome of this study was the overall incidence of hypotension during general anesthesia. RESULTS: Patients in the propofol group experienced higher intraoperative hypotension than those in the remimazolam group (59.7% vs 33.3%, P = .006). Multivariate logistic regression analysis showed that remimazolam administration was associated with reduced hypotension (adjusted odds ratio, 0.34; 95% CI, 0.16-0.73). Secondary outcomes such as recovery time, delirium, and postoperative nausea and vomiting were comparable in both groups. CONCLUSION: Total intravenous anesthesia with remimazolam was associated with less intraoperative hypotension than propofol in older patients, with a comparable recovery profile.

Genomic insight into the salt tolerance and proteolytic activity of Bacillus subtilis.

We assessed the salt tolerance and proteolytic activity of 40 genome-published Bacillus subtilis strains isolated from fermented Korean foods to illuminate the genomic background behind the functionality of B. subtilis in high-salt fermentation. On the basis of the salt tolerance and phenotypic proteolytic activity of the 40 strains, we selected five strains exhibiting different phenotypic characteristics. Comparative genomic analyses of these five strains provided genomic insight into the salt tolerance and proteolytic activity of B. subtilis. Two-component system (TCS) genes annotated as ybdGJK and laterally acquired authentic ATP-binding cassette (ABC) transporter system genes of tandem repeat structure might contribute to increase salt tolerance. The additional possession of gene homologs for CAAX protease family proteins and components of Clp (caseinolytic protease) complex, ATP-dependent Clp proteolytic subunit ClpP and AAA+ (ATPases associated with diverse cellular Activities) family ATPases, might determine the proteolytic activity of B. subtilis. This study established the scientific foundation for the viability and functionality of B. subtilis in high-salt fermentation.

Effect of oxygen vacancy and Si doping on the electrical properties of Ta2O5 in memristor characteristics.

The resistive switching behavior in Ta2O5 based memristors is largely controlled by the formation and annihilation of conductive filaments (CFs) that are generated by the migration of oxygen vacancies (OVs). To gain a fundamental insight on the switching characteristics, we have systematically investigated the electrical transport properties of two different Ta2O5 polymorphs ([Formula: see text]-Ta2O5 and λ-Ta2O5), using density functional theory calculations, and associated vacancy induced electrical conductivity using Boltzmann transport theory. The projected band structure and DOS in a few types of OVs, (two-fold (O2fV), three-fold (O3fV), interlayer (OILV), and distorted octahedral coordinated vacancies (OεV)) reveal that the presence of OILV would cause Ta2O5 to transition from a semiconductor to a metal, leading to improved electrical conductivity, whereas the other OV types only create localized mid-gap defect states within the bandgap. On studying the combined effect of OVs and Si-doping, a reduction of the formation energy and creation of defect states near the conduction band edge, is observed in Si-doped Ta2O5, and lower energy is found for the OVs near Si atoms, which would be advantageous to the uniformity of CFs produced by OVs. These findings can serve as guidance for further experimental work aimed at enhancing the uniformity and switching properties of resistance switching for Ta2O5-based memristors.

Clinical Outcomes of Upfront Primary Tumor Resection in Synchronous Unresectable Metastatic Colorectal Cancer.

The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group (n = 42) showed better performance (p = 0.061), had higher frequencies of right-sided origin (p = 0.058), the T4 stage (p = 0.003), the M1a stage (p = 0.012), and <2 organ metastases (p = 0.002), and received fewer targeted agents (p = 0.011) than the chemotherapy group (n = 163). The PTR group showed a trend for longer OS (20.5 versus 16.0 months, p = 0.064) but was not related to OS in Cox regression multivariate analysis (p = 0.220). The male sex (p = 0.061), a good performance status (p = 0.078), the T3 stage (p = 0.060), the M1a stage (p = 0.042), <2 organ metastases (p = 0.035), an RAS wild tumor (p = 0.054), and the administration of targeted agents (p = 0.037), especially bevacizumab (p = 0.067), seemed to be related to PTR benefits. Upfront PTR could be considered beneficial in some subgroups, but these findings require larger studies to verify.

A Study on Survival Analysis Methods Using Neural Network to Prevent Cancers.

Background: Cancer is one of the main global health threats. Early personalized prediction of cancer incidence is crucial for the population at risk. This study introduces a novel cancer prediction model based on modern recurrent survival deep learning algorithms. Methods: The study includes 160,407 participants from the blood-based cohort of the Korea Cancer Prevention Research-II Biobank, which has been ongoing since 2004. Data linkages were designed to ensure anonymity, and data collection was carried out through nationwide medical examinations. Predictive performance on ten cancer sites, evaluated using the concordance index (c-index), was compared among nDeep and its multitask variation, Cox proportional hazard (PH) regression, DeepSurv, and DeepHit. Results: Our models consistently achieved a c-index of over 0.8 for all ten cancers, with a peak of 0.8922 for lung cancer. They outperformed Cox PH regression and other survival deep neural networks. Conclusion: This study presents a survival deep learning model that demonstrates the highest predictive performance on censored health dataset, to the best of our knowledge. In the future, we plan to investigate the causal relationship between explanatory variables and cancer to reduce cancer incidence and mortality.

Correction to: Food-derived coagulase-negative Staphylococcus as starter cultures for fermented foods.

[This corrects the article DOI: 10.1007/s10068-020-00789-5.].

Overcoming field variability: unsupervised domain adaptation for enhanced crop-weed recognition in diverse farmlands.

Recent developments in deep learning-based automatic weeding systems have shown promise for unmanned weed eradication. However, accurately distinguishing between crops and weeds in varying field conditions remains a challenge for these systems, as performance deteriorates when applied to new or different fields due to insignificant changes in low-level statistics and a significant gap between training and test data distributions. In this study, we propose an approach based on unsupervised domain adaptation to improve crop-weed recognition in new, unseen fields. Our system addresses this issue by learning to ignore insignificant changes in low-level statistics that cause a decline in performance when applied to new data. The proposed network includes a segmentation module that produces segmentation maps using labeled (training field) data while also minimizing entropy using unlabeled (test field) data simultaneously, and a discriminator module that maximizes the confusion between extracted features from the training and test farm samples. This module uses adversarial optimization to make the segmentation network invariant to changes in the field environment. We evaluated the proposed approach on four different unseen (test) fields and found consistent improvements in performance. These results suggest that the proposed approach can effectively handle changes in new field environments during real field inference.

Staphylococcus equorum plasmid pKS1030-3 encodes auxiliary biofilm formation and trans-acting gene mobilization systems.

The foodborne bacterium Staphylococcus equorum strain KS1030 harbours plasmid pSELNU1, which encodes a lincomycin resistance gene. pSELNU1 undergoes horizontal transfer between bacterial strains, thus spreading antibiotic resistance. However, the genes required for horizontal plasmid transfer are not encoded in pSELNU1. Interestingly, a relaxase gene, a type of gene related to horizontal plasmid transfer, is encoded in another plasmid of S. equorum KS1030, pKS1030-3. The complete genome of pKS1030-3 is 13,583 bp long and encodes genes for plasmid replication, biofilm formation (the ica operon), and horizontal gene transfer. The replication system of pKS1030-3 possesses the replication protein-encoding gene repB, a double-stranded origin of replication, and two single-stranded origins of replication. The ica operon, relaxase gene, and a mobilization protein-encoding gene were detected in pKS1030-3 strain-specifically. When expressed in S. aureus RN4220, the ica operon and relaxase operon of pKS1030-3 conferred biofilm formation ability and horizontal gene transfer ability, respectively. The results of our analyses show that the horizontal transfer of pSELNU1 of S. equorum strain KS1030 depends on the relaxase encoded by pKS1030-3, which is therefore trans-acting. Genes encoded in pKS1030-3 contribute to important strain-specific properties of S. equorum KS1030. These results could contribute to preventing the horizontal transfer of antibiotic resistance genes in food.

From Solution to Thin Film: Molecular Assembly of π-Conjugated Systems and Impact on (Opto)electronic Properties.

The assembly of conjugated organic molecules from solution to solid-state plays a critical role in determining the thin film morphology and optoelectronic properties of solution-processed organic electronics and photovoltaics. During evaporative solution processing, π-conjugated systems can assemble via various forms of intermolecular interactions, forming distinct aggregate structures that can drastically tune the charge transport landscape in the solid-state. In blend systems composed of donor polymer and acceptor molecules, assembly of neat materials couples with phase separation and crystallization processes, leading to complex phase transition pathways which govern the blend film morphology. In this review, we provide an in-depth review of molecular assembly processes in neat conjugated polymers and nonfullerene small molecule acceptors and discuss their impact on the thin film morphology and optoelectronic properties. We then shift our focus to blend systems relevant to organic solar cells and discuss the fundamentals of phase transition and highlight how the assembly of neat materials and processing conditions can affect blend morphology and device performance.

ComQXPA quorum-sensing systems contribute to enhancing the protease activity of Bacillus velezensis DMB05 from fermented soybeans.

Bacillus velezensis DMB05, isolated from traditionally fermented soybean, meju, exhibited no protease activity on a TSA plate containing skim milk. To shed light on the genetic background behind this phenotypic non-protease activity, we analyzed the complete genome sequence of strain DMB05 and compared it with those of two B. velezensis strains which did exhibit protease activity. Comparative genome analyses showed no significant difference in the kind or number of proteases between the genomes of the three strains and that all strains possessed the degSU two-component system involved in the gene regulation of protease. However, strain DMB05 possessed a truncated comP which is part of the comQXPA operon that regulates the expression of degQ involved in the activation of DegSU. When the entire comQXPA operon derived from DMB06 was introduced into DMB05, the recombinant expressed proteolytic activity. The results of this experimental study provide evidence for the presence of regulatory genes involved in protease activity, one of several important factors involved in fermentation.

Materials Innovations for Quantum Technology Acceleration: A Perspective.

A broad perspective of quantum technology state of the art is provided and critical stumbling blocks for quantum technology development are identified. Innovations in demonstrating and understanding electron entanglement phenomena using bulk and low-dimensional materials and structures are summarized. Correlated photon-pair generation via processes such as nonlinear optics is discussed. Application of qubits to current and future high-impact quantum technology development is presented. Approaches for realizing unique qubit features for large-scale encrypted communication, sensing, computing, and other technologies are still evolving; thus, materials innovation is crucially important. A perspective on materials modeling approaches for quantum technology acceleration that incorporate physics-based AI/ML, integrated with quantum metrology is discussed.

Highly Porous Carbon Aerogels for High-Performance Supercapacitor Electrodes.

In recent years, porous carbon materials with high specific surface area and porosity have been developed to meet the commercial demands of supercapacitor applications. Carbon aerogels (CAs) with three-dimensional porous networks are promising materials for electrochemical energy storage applications. Physical activation using gaseous reagents provides controllable and eco-friendly processes due to homogeneous gas phase reaction and removal of unnecessary residue, whereas chemical activation produced wastes. In this work, we have prepared porous CAs activated by gaseous carbon dioxide, with efficient collisions between the carbon surface and the activating agent. Prepared CAs display botryoidal shapes resulting from aggregation of spherical carbon particles, whereas activated CAs (ACAs) display hollow space and irregular particles from activation reactions. ACAs have high specific surface areas (2503 m2 g-1) and large total pore volumes (1.604 cm3 g-1), which are key factors for achieving a high electrical double-layer capacitance. The present ACAs achieved a specific gravimetric capacitance of up to 89.1 F g-1 at a current density of 1 A g-1, along with a high capacitance retention of 93.2% after 3000 cycles.

Quality characteristics of soybean fermented by Mucor, Rhizopus, and Aspergillus from meju.

Three candidate starter strains-Aspergillus oryzae SNU-G, Mucor sp. KACC 46077, and Rhizopus oryzae KACC 40256-were inoculated into soybean, as individual strains or in combination, to assess their roles in fermentation. All the strains increased the pH, amino-type nitrogen, and moisture content of the soybean during fermentation, and decreased the lightness, redness, and yellowness. The inoculated strains increased to an average density of 1.37 × 108 spores/g (from the initial 5.0 × 107 spores/g) after 20 days of fermentation. Forty-two volatile compounds, including an acid, alcohols, carbonyls, furans, and a pyrazine, were more abundant in soybean fermented with starters than in controls. A. oryzae SNU-G increased the pH more than the other strains and produced more volatile alcohol compounds. R. oryzae KACC 40256 resulted in the lowest reduction of redness and yellowness during the fermentation and produced large amounts of carbonyl compounds, including two specific volatile compounds, 2-hydroxy-3-methylcyclopent-2-en-1-one and (3E)-3-ethyl-2-methylhexa-1,3-diene. Mucor sp. KACC 46077 contributed the least to pH change and volatile compound production, and did not produce specific volatile compounds. Although no significant synergy in the production of volatile compounds was found when using mixtures of strains compared with application of single strains, the quality of fermented soybeans was confirmed to be different depending on the strain(s) applied.

Increased Production of γ-Aminobutyric Acid from Brewer's Spent Grain Through Bacillus Fermentation.

Brewer's spent grain (BSG) is a waste product of the beer industry, and γ-aminobutyric acid (GABA) is a physiologically active substance important for brain and neuron physiology. In this study, we used the bacterial strains Bacillus velezensis DMB06 and B. licheniformis 0DA23-1, respectively, to ferment BSG and produce GABA. The GABA biosynthesis pathways were identified through genomic analysis of the genomes of both strains. We then inoculated the strains into BSG to determine changes in pH, acidity, reducing sugar content, amino-type nitrogen content, and GABA production, which was approximately doubled in BSG inoculated with Bacillus compared to that in uninoculated BSG; however, no significant difference was observed in GABA production between the two bacterial strains. These results provide the experimental basis for expanding the use of BSG by demonstrating the potential gain in increasing GABA production from a waste resource.

Comparison of four multilocus sequence typing schemes and amino acid biosynthesis based on genomic analysis of Bacillus subtilis.

Bacillus subtilis, a valuable industrial microorganism used in starter cultures in soybean fermentation, is a species of bacteria with interspecies diversity. Here, four multilocus sequence typing (MLST) schemes developed to assess the diversity of B. subtilis or Bacillus spp. were applied and compared to confirm the interspecies diversity of B. subtilis. In addition, we analyzed correlations between amino acid biosynthesis genes and sequence types (STs); this is important because amino acids are key taste components in fermented foods. On applying the four MLST methods to 38 strains and the type strain of B. subtilis, 30 to 32 STs were identified. The discriminatory power was 0.362-0.964 for the genes used in the MLST methods; the larger the gene, the greater the number of alleles and polymorphic sites. All four MLST methods showed a correlation between STs and strains that do not possess the hutHUIG operon (which contains genes required for the production of glutamate from histidine). This correlation was verified using 168 further genome-sequence strains.