Multivariate modular metabolic engineering and medium optimization for vitamin B12 production by Escherichia coli.

Vitamin B12 is a complex compound synthesized by microorganisms. The industrial production of vitamin B12 relies on specific microbial fermentation processes. E. coli has been utilized as a host for the de novo biosynthesis of vitamin B12, incorporating approximately 30 heterologous genes. However, a metabolic imbalance in the intricate pathway significantly limits vitamin B12 production. In this study, we employed multivariate modular metabolic engineering to enhance vitamin B12 production in E. coli by manipulating two modules comprising a total of 10 genes within the vitamin B12 biosynthetic pathway. These two modules were integrated into the chromosome of a chassis cell, regulated by T7, J23119, and J23106 promoters to achieve combinatorial pathway optimization. The highest vitamin B12 titer was attained by engineering the two modules controlled by J23119 and T7 promoters. The inclusion of yeast powder to the fermentation medium increased the vitamin B12 titer to 1.52 mg/L. This enhancement was attributed to the effect of yeast powder on elevating the oxygen transfer rate and augmenting the strain's isopropyl-ß-d-1-thiogalactopyranoside (IPTG) tolerance. Ultimately, vitamin B12 titer of 2.89 mg/L was achieved through scaled-up fermentation in a 5-liter fermenter. The strategies reported herein will expedite the development of industry-scale vitamin B12 production utilizing E. coli.

Genome-wide identification and evolutionary analysis of the NRAMP gene family in the AC genomes of Brassica species.

BACKGROUND: Brassica napus, a hybrid resulting from the crossing of Brassica rapa and Brassica oleracea, is one of the most important oil crops. Despite its significance, B. napus productivity faces substantial challenges due to heavy metal stress, especially in response to cadmium (Cd), which poses a significant threat among heavy metals. Natural resistance-associated macrophage proteins (NRAMPs) play pivotal roles in Cd uptake and transport within plants. However, our understanding of the role of BnNRAMPs in B. napus is limited. Thus, this study aimed to conduct genome-wide identification and bioinformatics analysis of three Brassica species: B. napus, B. rapa, and B. oleracea. RESULTS: A total of 37 NRAMPs were identified across the three Brassica species and classified into two distinct subfamilies based on evolutionary relationships. Conservative motif analysis revealed that motif 6 and motif 8 might significantly contribute to the differentiation between subfamily I and subfamily II within Brassica species. Evolutionary analyses and chromosome mapping revealed a reduction in the NRAMP gene family during B. napus evolutionary history, resulting in the loss of an orthologous gene derived from BoNRAMP3.2. Cis-acting element analysis suggested potential regulation of the NRAMP gene family by specific plant hormones, such as abscisic acid (ABA) and methyl jasmonate (MeJA). However, gene expression pattern analyses under hormonal or stress treatments indicated limited responsiveness of the NRAMP gene family to these treatments, warranting further experimental validation. Under Cd stress in B. napus, expression pattern analysis of the NRAMP gene family revealed a decrease in the expression levels of most BnNRAMP genes with increasing Cd concentrations. Notably, BnNRAMP5.1/5.2 exhibited a unique response pattern, being stimulated at low Cd concentrations and inhibited at high Cd concentrations, suggesting potential response mechanisms distinct from those of other NRAMP genes. CONCLUSIONS: In summary, this study indicates complex molecular dynamics within the NRAMP gene family under Cd stress, suggesting potential applications in enhancing plant resilience, particularly against Cd. The findings also offer valuable insights for further understanding the functionality and regulatory mechanisms of the NRAMP gene family.

Isoflurane pretreatment protects against myocardial ischemia/reperfusion injury via mediating lncRNA CASC15/miR-542-3p axis.

The protective effect of isoflurane on cardiomyocyte ischemia/reperfusion injury (I/RI) was explored in hypoxia and reoxygenation (H/R) induced cardiomyocyte injury model. In terms of mechanism, the participation of long non-coding RNA CASC15/microR-542-3p axis was further discussed. H9c2 cells received H/R treatment to mimic myocardial I/RI. RT-qPCR was performed to quantify mRNA levels. Cell viability and apoptosis were evaluated after isoflurane pretreatment and cell transfection. ELISA was performed to measure the concentrations of inflammatory/oxidative stress-related cytokines (TNF-α, IL-6, MDA, SOD). The target relationship between CASC12 and miR-542-3p was determined via dual-luciferase reporter assay. Isoflurane pretreatment alleviated H/R-induced cell viability suppression and cell apoptosis promotion, which was accompanied by CASC15 downregulation. CASC15 overexpression abolished the influence of isoflurane on cardiomyocytes' viability and apoptosis. H/R-induced excessive release of TNF-α and IL-6 was hold down by isoflurane, which was re-activated after CASC15 overexpression. The concentration changes of both MDA and SOD by isoflurane were reversed by CASC15 overexpression. CASC15 functioned as miR-542-3p sponger, and miR-542-3p overexpression attenuated the effect of isoflurane and CASC15 on H/R-induced cardiac I/RI. Isoflurane pretreatment was beneficial for the alleviation of cardiac I/RI by inhibiting oxidative stress and myocardial inflammatory response. CASC15/miR-542-3p axis was required for isoflurane to exhibit its protective activity against cardiac I/RI.

Engineering and finetuning expression of SerC for balanced metabolic flux in vitamin B6 production.

Vitamin B6 plays a crucial role in cellular metabolism and stress response, making it an essential component for growth in all known organisms. However, achieving efficient biosynthesis of vitamin B6 faces the challenge of maintaining a balanced distribution of metabolic flux between growth and production. In this study, our focus is on addressing this challenge through the engineering of phosphoserine aminotransferase (SerC) to resolve its redundancy and promiscuity. The enzyme SerC was semi-designed and screened based on sequences and predicted kcat values, respectively. Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B6. The resulting strain enhances the production of vitamin B6, indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B6. This study presents a promising strategy to address the challenge posed by multifunctional enzymes, with significant implications for enhancing biochemical production through engineering processes.

Recent Advances in the Crosstalk between Brassinosteroids and Environmental Stimuli.

Due to their sessile lifestyle, plants need to optimize their growth in order to adapt to ever-changing environments. Plants receive stimuli from the environment and convert them into cellular responses. Brassinosteroids (BRs), as growth-promoting steroid hormones, play a significant role in the tradeoff between growth and environmental responses. Here, we provide a comprehensive summary for understanding the crosstalk between BR and various environmental stresses, including water availability, temperature fluctuations, salinization, nutrient deficiencies and diseases. We also highlight the bottlenecks that need to be addressed in future studies. Ultimately, we suppose to improve plant environmental adaptability and crop yield by excavating natural BR mutants or modifying BR signaling and its targets.

Sleep Quality and Suicidal Ideation in Adolescent Depression: A Chain Mediation Effect of Perceived Social Support and Resilience.

BACKGROUND: The prevalence of suicide is high among major depressive adolescents. Poor sleep quality has been documented as a significant risk factor for suicide, influencing perceived social support. Enhanced social support acts as a buffer against suicidal ideation and positively impacts resilience, reducing the prevalence of suicidal ideation. This reciprocal relationship between sleep quality, social support and resilience forms the basis for understanding the mechanisms contributing to suicidal ideation in major depressive adolescents. METHODS: A total of 585 major depressive adolescents aged 11 to 24 years was conducted to explore these associations. Assessments included the Pittsburgh Sleep Quality Index, Multidimensional Scale of Perceived Social Support, Connor-Davidson Resilience Scale and Beck Scale for Suicide Ideation. Pearson correlation and Model 6 in the SPSS program were employed for chain mediating tests. RESULTS: Better sleep quality positively predicted decreased suicide ideation (ß = 0.207, p < 0.01) and predicted lower perceived social support (ß = -0.226, p < 0.01) and resilience (ß = -0.355, p < 0.01). Perceived social support positively predicted increased resilience (ß = 0.422, p < 0.01) and negatively predicted suicide ideation (ß = -0.288, p < 0.01). Resilience negatively predicted suicide ideation (ß = -0.187, p < 0.01). Sleep quality indirectly predicted suicide ideation through perceived social support and resilience, with a mediation value of 0.0678 (95% CI [0.0359, 0.1060]), constituting 10.65% of the total effect. CONCLUSIONS: This study establishes that sleep quality indirectly predicts suicide ideation in major depressive adolescents, mediated independently by perceived social support and resilience.

Structural identification and anti-neuroinflammatory effects of a pectin-arabinoglucuronogalactan complex, AOPB-1-1, isolated from Asparagus officinalis.

Asparagus officinalis L. is a horticultural crop that contains a variety of bioactive compounds with anti-inflammatory effects. Aqueous extracts of A. officinalis can noticeably improve the learning and memory function of model mice. Herein, a pectin-arabinoglucuronogalactan complex (AOPB-1-1) with a relative molecular weight of 90.8 kDa was isolated from A. officinalis. The repeating structural unit of AOPB-1-1 was identified through monosaccharide composition, methylation analysis, uronic acid reduction, partial acid hydrolysis, and nuclear magnetic resonance spectroscopy. AOPB-1-1 contains the rhamnogalacturonan-I (RG-I) domain of pectin polysaccharides (PPs) and arabinoglucuronogalactan (AGG) regions. The backbone of the AGG region is composed of →3,6)-ß-D-Galp-(1 → and →4)-ß-D-Glcp-(1 → residues substituted at the 4-position to the →4)-α-D-GalAp-(1 → residues of the RG-I main chain. The anti-neuroinflammatory activity of AOPB-1-1 suggests that it can significantly reduce the content of inflammatory cytokines, including nitric oxide, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibit the expression of inflammatory genes including cyclooxygenase-2, nitric oxide synthase, TNF-α, IL-6, and interleukin-1ß in LPS-stimulated BV2 cells. Furthermore, its inhibitory effects on TNF-α and IL-6 levels were even better than those of minocycline. The significant anti-neuroinflammatory activity of AOPB-1-1 suggests its applicability as a therapeutic option for the treatment of Alzheimer's disease.

Catalyzing satellite communication: A 20W Ku-Band RF front-end power amplifier design and deployment.

This paper presents a groundbreaking Ku-band 20W RF front-end power amplifier (PA), designed to address numerous challenges encountered by satellite communication systems, including those pertaining to stability, linearity, cost, and size. The manuscript commences with an exhaustive discussion of system design and operational principles, emphasizing the intricacies of low-noise amplification, and incorporating key considerations such as noise factors, stability analysis, gain, and gain flatness. Subsequently, an in-depth study is conducted on various components of the RF chain, including the pre-amplification module, driver-amplification module, and final-stage amplification module. The holistic design extends to the inclusion of the display and control unit, featuring the power-control module, monitoring module, and overall layout design of the PA. It is meticulously tailored to meet the specific demands of satellite communication. Following this, a thorough exploration of electromagnetic simulation and measurement results ensues, providing validation for the precision and reliability of the proposed design. Finally, the feasibility of that design is substantiated through systematic system design, prototype production, and exhaustive experimental testing. It is noteworthy that, in the space-simulation environmental test, emphasis is placed on the excellent performance of the Star Ku-band PA within the 13.75GHz to 14.5GHz frequency range. Detailed power scan measurements reveal a P1dB of 43dBm, maintaining output power flatness < ± 0.5dBm across the entire frequency and temperature spectrum. Third-order intermodulation scan measurements indicate a third-order intermodulation of ≤ -23dBc. Detailed results of power monitoring demonstrate a range from +18dBm to +54dBm. Scans of spurious suppression and harmonic suppression, meanwhile, show that the PA evinces spurious suppression ≤ -65dBc and harmonic suppression ≤ -60dBc. Rigorous phase-scan measurements exhibit a phase-shift adjustment range of 0° to 360°, with a step of 5.625°, and a phase-shift accuracy of 0.5dB. Detailed data from gain-scan measurements show a gain-adjustment range of 0dB to 30dB, with a gain flatness of ± 0.5dB. Attenuation error is ≤ 1%. These test parameters perfectly align with the practical application requirements of the technical specifications. When compared to existing Ku-band PAs, our design reflects a deeper consideration of specific requirements in satellite communication, ensuring its outstanding performance and uniqueness. This PA features good stability, high linearity, low cost, and compact modularity, ensuring continuous and stable power output. These features position the proposed system as a leader within the market. Successful orbital deployment not only validates its operational stability; it also makes a significant contribution to the advancement of China's satellite PA technology, generating positive socio-economic benefits.

Structural identification and anti-neuroinflammatory effect of a heteropolysaccharide ATP50-3 from Acorus tatarinowii rhizome.

Acorus tatarinowii, a famous traditional Chinese medicine, is used for the clinical treatment of memory impairment and dementia. In this research, AT50, the crude polysaccharide extracted from A. tatarinowii rhizome, significantly improved the memory and learning ability of mice with Alzheimer's disease (AD) and exerted excellent anti-neuroinflammatory effects. More importantly, AT50 returned the levels of NO, TNF-α, IL-1ß, PGE-2, and IL-6 in AD mouse brains to normal levels. To identify the active ingredients in AT50, a heteropolysaccharide ATP50-3 was obtained from AT50. Structural analysis indicated ATP50-3 consisted of α-L-Araf-(1→, →2)-α-L-Araf-(1→, →3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, α-D-Xylp-(1→, →3,4)-ß-D-Xylp-(1→, →3)-α-D-Galp-(1→, →3,6)-α-D-Galp-(1→, →6)-4-OAc-α-D-Galp-(1→, →3,4,6)-α-D-Galp-(1→, →4)-α-D-Glcp-(1→, →2,3,6)-ß-D-Glcp-(1→, →4,6)-α-D-Manp-(1→, →3,4)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →4)-α-D-GlcpA-(1 â†’ residues and terminated with Xyl and Ara. Additionally, ATP50-3 significantly inhibited the release of proinflammatory factors in lipopolysaccharide-stimulated BV2 cells. ATP50-3 may be an active constituent of AT50, responsible for its anti-neuroinflammatory effects, with great potential to treat AD.

Optical Temperature-Sensing Performance of La2Ce2O7:Ho3+ Yb3+ Powders.

In this paper, La2Ce2O7 powders co-activated by Ho3+ and Yb3+ were synthesized by a high temperature solid-state reaction. Both Ho3+ and Yb3+ substitute the La3+ sites in the La2Ce2O7 lattice, where the Ho3+ concentration is 0.5 at.% and the Yb3+ concentration varies in the range of 10~18% at.%. Pumped by a 980 nm laser, the up-conversion (UC) green emission peak at 547 nm and the red emission at 661 nm were detected. When the doping concentration of Ho3+ and Yb3+ are 0.5 at.% and 14% at.%, respectively, the UC emission reaches the strongest intensity. The temperature-sensing performance of La2Ce2O7:Ho3+ with Yb3+ was studied in the temperature range of 303-483 K, where the highest relative sensitivity (Sr) is 0.0129 K-1 at 483 K. The results show that the powder La2Ce2O7:Ho3+, Yb3+ can be a potential candidate for remote temperature sensors.

Metabolome and transcriptome analyses reveal changes of rapeseed in response to ABA signal during early seedling development.

Seed germination is an important development process in plant growth. The phytohormone abscisic acid (ABA) plays a critical role during seed germination. However, the mechanism of rapeseed in response to ABA is still elusive. In order to understand changes of rapeseed under exogenous ABA treatment, we explored differentially expressed metabolites (DEMs) and the differentially expressed genes (DEGs) between mock- and ABA-treated seedlings. A widely targeted LC-MS/MS based metabolomics were used to identify and quantify metabolic changes in response to ABA during seed germination, and a total of 186 significantly DEMs were identified. There are many compounds which are involved in ABA stimuli, especially some specific ABA transportation-related metabolites such as starches and lipids were screened out. Meanwhile, a total of 4440 significantly DEGs were identified by transcriptomic analyses. There was a significant enrichment of DEGs related to phenylpropanoid and cell wall organization. It suggests that exogenous ABA mainly affects seed germination by regulating cell wall loosening. Finally, the correlation analysis of the key DEMs and DEGs indicates that many DEGs play a direct or indirect regulatory role in DEMs metabolism. The integrative analysis between DEGs and DEMs suggests that the starch and sucrose pathways were the key pathway in ABA responses. The two metabolites from starch and sucrose pathways, levan and cellobiose, both were found significantly down-regulated in ABA-treated seedlings. These comprehensive metabolic and transcript analyses provide useful information for the subsequent post-transcriptional modification and post germination growth of rapeseed in response to ABA signals and stresses.

Longitudinal polarization manipulation based on all-dielectric terahertz metasurfaces.

Polarization modulation of electromagnetic waves plays an important role in the field of optics and optoelectronics. Current polarization optics are typically limited to the modulation in a single transverse plane. However, manipulating polarization along the longitudinal direction is also important for full-space polarization modulation. Here, we propose two kinds of all-dielectric terahertz metasurfaces for longitudinally spatial polarization manipulation. The metasurfaces are capable of controlling polarization along the propagation path, namely: i) a longitudinal bifocal metalens with different polarization states at each focal point, and ii) a versatile metalens can simultaneously generate a uniformly polarized focused beam and a vector beam with varying polarization along the propagation path. Furthermore, the measurement of the dielectric thickness is demonstrated based on the polarization modulation feature of the metalens. The proposed metasurfaces allow for effective polarization state alteration along the propagation path, exhibiting significant potential for applications in versatile light-matter interactions, optical communications, and quantum optics.

A rapid and low-cost platform for detection of bacterial based on microchamber PCR microfluidic chip.

Polymerase chain reaction (PCR) has been considered as the gold standard for detecting nucleic acids. The simple PCR system is of great significance for medical applications in remote areas, especially for the developing countries. Herein, we proposed a low-cost self-assembled platform for microchamber PCR. The working principle is rotating the chamber PCR microfluidic chip between two heaters with fixed temperature to solve the problem of low temperature variation rate. The system consists of two temperature controllers, a screw slide rail, a chamber array microfluidic chip and a self-built software. Such a system can be constructed at a cost of about US$60. The micro chamber PCR can be finished by rotating the microfluidic chip between two heaters with fixed temperature. Results demonstrated that the sensitivity of the temperature controller is 0.1℃. The relative error of the duration for the microfluidic chip was 0.02 s. Finally, we successfully finished amplification of the target gene of Porphyromonas gingivalis in the chamber PCR microfluidic chip within 35 min and on-site detection of its PCR products by fluorescence. The chip consisted of 3200 cylindrical chambers. The volume of reagent in each volume is as low as 0.628 nL. This work provides an effective method to reduce the amplification time required for micro chamber PCR.

Robust Cooperative Control for Heterogeneous Uncertain Nonlinear High-Order Fully Actuated Multiagent Systems.

This research is intended to address a robust cooperative control problem of heterogeneous uncertain nonlinear high-order fully actuated multiagent systems (HUN-HOFAMASs). A nonlinear HOFA system model is used to describe the multiagent systems (MASs) with heterogeneous uncertain nonlinear dynamics, which is called the HUN-HOFAMASs. A predictive terminal sliding-mode control-based robust cooperative control scheme is presented to address this problem. In this scheme, heterogeneous nonlinear dynamics of original system are offset to establish a linear constant HOFA system with the help of full actuation feature. Then, a terminal sliding-mode variable for enhancing the system robustness is introduced to handle the uncertainties. Furthermore, a linear incremental prediction model is developed in a HOFA form by means of a Diophantine equation. According to this model, the multistep terminal sliding-mode predictions are yielded to optimize the robust cooperative control performance and compensate for the network-induced communication constraints in the feedback and forward channels. Based on a linear matrix inequality (LMI) method, a necessary and sufficient criterion is derived to discuss the simultaneous consensus and stability of closed-loop HUN-HOFAMASs. The simulation and comparison results of cooperative flying around of multiple spacecraft system are shown to illustrate the capability and advantage of the presented predictive terminal sliding-mode control for robust cooperative control.

External Stimuli-Induced Welding of Dynamic Cross-Linked Polymer Networks.

Thermosets have been crucial in modern engineering for decades, finding applications in various industries. Welding cross-linked components are essential in the processing of thermosets for repairing damaged areas or fabricating complex structures. However, the inherent insolubility and infusibility of thermoset materials, attributed to their three-dimensional network structure, pose challenges to welding development. Incorporating dynamic chemical bonds into highly cross-linked networks bridges the gap between thermosets and thermoplastics presenting a promising avenue for innovative welding techniques. External stimuli, including thermal, light, solvent, pH, electric, and magnetic fields, induce dynamic bonds' breakage and reformation, rendering the cross-linked network malleable. This plasticity facilitates the seamless linkage of two parts to an integral whole, attracting significant attention for potential applications in soft actuators, smart devices, solid batteries, and more. This review provides a comprehensive overview of dynamic bonds employed in welding dynamic cross-linked networks (DCNs). It extensively discusses the classification and fabrication of common epoxy DCNs and acrylate DCNs. Notably, recent advancements in welding processes based on DCNs under external stimuli are detailed, focusing on the welding dynamics among covalent adaptable networks (CANs).

The Influence of an Unsupported Sleeper on the Vertical Bearing Characteristics of Heavy-Haul Railway Ballast.

In order to study the influence of an unsupported sleeper on the vertical bearing characteristics of heavy-haul railway ballast, a three-dimensional discrete element model (DEM) was established for a ballasted track, by removing ballast particles that come into contact with the bottom of the sleeper from the model to simulate the unsupported sleeper. Vertical bearing characteristics for ballast on different types of unsupported sleepers were studied. The results showed that an unsupported sleeper could reduce the bearing area of the ballast below the sleeper and reduce the number of ballast particles that were in contact. It could also lead to an increase in the maximum contact force between the particles, accelerating the deterioration of the particles (thus affecting the overall performance of the ballast) and reducing the vertical stiffness of the ballast. As the unsupported length and width increased, vertical stiffness gradually decreased. The vertical ballast stiffness for an unsupported sleeper was then used in a dynamic coupled vehicle/track model, and the effect of the unsupported sleeper on wheel/rail interaction was analyzed. Results showed that increasing the unsupported length and width leads to a decrease in the supporting force on the unsupported sleeper and to an increase in the supporting force on the adjacent sleepers.

Revolutionizing cancer treatment: enhancing CAR-T cell therapy with CRISPR/Cas9 gene editing technology.

CAR-T cell therapy, a novel immunotherapy, has made significant breakthroughs in clinical practice, particularly in treating B-cell-associated leukemia and lymphoma. However, it still faces challenges such as poor persistence, limited proliferation capacity, high manufacturing costs, and suboptimal efficacy. CRISPR/Cas system, an efficient and simple method for precise gene editing, offers new possibilities for optimizing CAR-T cells. It can increase the function of CAR-T cells and reduce manufacturing costs. The combination of CRISPR/Cas9 technology and CAR-T cell therapy may promote the development of this therapy and provide more effective and personalized treatment for cancer patients. Meanwhile, the safety issues surrounding the application of this technology in CAR-T cells require further research and evaluation. Future research should focus on improving the accuracy and safety of CRISPR/Cas9 technology to facilitate the better development and application of CAR-T cell therapy. This review focuses on the application of CRISPR/Cas9 technology in CAR-T cell therapy, including eliminating the inhibitory effect of immune checkpoints, enhancing the ability of CAR-T cells to resist exhaustion, assisting in the construction of universal CAR-T cells, reducing the manufacturing costs of CAR-T cells, and the security problems faced. The objective is to show the revolutionary role of CRISPR/Cas9 technology in CAR-T cell therapy for researchers.

High-throughput 3D microfluidic chip for generation of concentration gradients and mixture combinations.

Concentration gradient generation and mixed combinations of multiple solutions are of great value in the field of biomedical research. However, existing concentration gradient generators for single or two-drug solutions cannot simultaneously achieve multiple concentration gradient formations and mixed solution combinations. Furthermore, the whole system was huge, and required expensive auxiliary equipment, which may lead to complex operations. To address this problem, we devised a novel 3D microchannel network design, which is capable of creating all the desired mixture combinations and concentration gradients of given small amounts of the input solutions. As a proof of concept, the device we presented was verified by both colorimetric and fluorescence detection methods to test the efficiency. This can enable the implementation of one to three solutions with no driving pump and facilitate unique multiple types of more concentration gradients and mixture combinations in a single operation. We envision that this will be a promising candidate for the development of simplified methods for screening of the appropriate concentration and combination, such as various drug screening applications.

Air-Liquid Interface Microfluidic Monitoring Sensor Platform for Studying Autophagy Regulation after PM2.5 Exposure.

Undoubtedly, a deep understanding of PM2.5-induced tumor metastasis at the molecular level can contribute to improving the therapeutic effects of related diseases. However, the underlying molecular mechanism of fine particle exposure through long noncoding RNA (lncRNA) regulation in autophagy and, ultimately, lung cancer (LC) metastasis remains elusive; on the other hand, the related monitoring sensor platform used to investigate autophagy and cell migration is lacking. Herein, this study performed an air-liquid interface microfluidic monitoring sensor (AIMMS) platform to analyze human bronchial epithelial cells after PM2.5 stimulation. The multiomics analysis [RNA sequencing (RNA-seq) on lncRNA and mRNA expressions separately] showed that MALAT1 was highly expressed in the PM2.5 treatment group. Furthermore, RNA-seq analysis demonstrated that autophagy-related pathways were activated. Notably, the main mRNAs associated with autophagy regulation, including ATG4D, ATG12, ATG7, and ATG3, were upregulated. Inhibition or downregulation of MALAT1 inhibited autophagy via the ATG4D/ATG12/ATG7/ATG3 pathway after PM2.5 exposure and ultimately suppressed LC metastasis. Thus, based on the AIMMS platform, we found that MALAT1 might become a promising therapeutic target. Furthermore, this low-cost AIMMS system as a fluorescence sensor integrated with the cell-monitor module could be employed to study LC migration after PM2.5 exposure. With the fluorescence cell-monitoring module, the platform could be used to observe the migration of LC cells and construct the tumor metastasis model. In the future, several fluorescence probes, including nanoprobes, could be used in the AIMMS platform to investigate many other biological processes, especially cell interaction and migration, in the fields of toxicology and pharmacology.

Engineering Domain Variants in 0.7Pb(Mg1/3Nb2/3)-0.3PbTiO3 Single Crystals Using High-Frequency AC Poling.

Single crystals of (001)-oriented 0.7Pb(Mg1/3Nb2/3)-0.3PbTiO3 (PMN-30PT) with a composition near the morphotropic phase boundary have attracted considerable attention due to their superior dielectric and electromechanical performance. Recently, a new alternating current (electric field) poling approach used for the enhancement of dielectric and piezoelectric properties. However, the microscopic domain variants that govern the performance, especially under high-frequency alternating current (AC) voltages, remain largely unexplored. In this work, the domain microstructure under AC poling reveals the presence of four monoclinic (MA) domain variants using a suite of scanning probe microscopy methods, and X-ray diffraction (XRD) reciprocal space mapping is tuned. It is reported on the emergence of hierarchical fine domains - needle-shaped, and 109° domain walls under applied high-frequency AC poling. Time-resolved Kelvin probe force microscopy (KPFM) reveals the charge dynamics and relaxation behavior of these needle domains and walls. The findings provide new insight and guidance to the domain engineering by high-frequency AC poling for the development of advanced transducer technology.