Circulating HMGB1 in acute ischemic stroke and its association with post-stroke cognitive impairment.

Background: Ischemic stroke frequently leads to a condition known as post-stroke cognitive impairment (PSCI). Timely recognition of individuals susceptible to developing PSCI could facilitate the implementation of personalized strategies to mitigate cognitive deterioration. High mobility group box 1 (HMGB1) is a protein released by ischemic neurons and implicated in inflammation after stroke. Circulating levels of HMGB1 could potentially serve as a prognostic indicator for the onset of cognitive impairment following ischemic stroke. Objective: To investigate the predictive value of circulating HMGB1 concentrations in the acute phase of ischemic stroke for the development of cognitive dysfunction at the 3-month follow-up. Methods: A total of 192 individuals experiencing their initial episode of acute cerebral infarction were prospectively recruited for this longitudinal investigation. Concentrations of circulating HMGB1 were quantified using an enzyme-linked immunosorbent assay (ELISA) technique within the first 24 hours following hospital admission. Patients underwent neurological evaluation including NIHSS scoring. Neuropsychological evaluation was conducted at the 3-month follow-up after the cerebrovascular event, employing the Montreal Cognitive Assessment (MoCA) as the primary tool for assessing cognitive performance. Multivariable logistic regression models were employed to investigate the relationship between circulating HMGB1 concentrations and cognitive dysfunction following stroke, which was operationalized as a MoCA score below 26, while controlling for potential confounders including demographic characteristics, stroke severity, vascular risk factors, and laboratory parameters. Results: Of 192 patients, 84 (44%) developed PSCI. Circulating HMGB1 concentrations were significantly elevated in individuals who developed cognitive dysfunction following stroke compared to those who maintained cognitive integrity (8.4 ± 1.2 ng/mL vs 4.6 ± 0.5 ng/mL, respectively; p < 0.001). The prevalence of PSCI showed a dose-dependent increase with higher HMGB1 quartiles. After controlling for potential confounders such as demographic factors (age, gender, and education), stroke severity, vascular risk factors, and laboratory parameters in a multivariable logistic regression model, circulating HMGB1 concentrations emerged as a significant independent predictor of cognitive dysfunction following stroke (regression coefficient = 0.236, p < 0.001). Conclusion: Circulating HMGB1 concentrations quantified within the first 24 hours following acute cerebral infarction are significantly and independently correlated with the likelihood of developing cognitive dysfunction at the 3-month follow-up, even after accounting for potential confounding factors. HMGB1 may be a novel biomarker to identify patients likely to develop post-stroke cognitive impairment for targeted preventive interventions.

CRISPR/Cas9 systems: Delivery technologies and biomedical applications.

The emergence of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing system has brought about a significant revolution in the realm of managing human diseases, establishing animal models, and so on. To fully harness the potential of this potent gene-editing tool, ensuring efficient and secure delivery to the target site is paramount. Consequently, developing effective delivery methods for the CRISPR/Cas9 system has become a critical area of research. In this review, we present a comprehensive outline of delivery strategies and discuss their biomedical applications in the CRISPR/Cas9 system. We also provide an in-depth analysis of physical, viral vector, and non-viral vector delivery strategies, including plasmid-, mRNA- and protein-based approach. In addition, we illustrate the biomedical applications of the CRISPR/Cas9 system. This review highlights the key factors affecting the delivery process and the current challenges facing the CRISPR/Cas9 system, while also delineating future directions and prospects that could inspire innovative delivery strategies. This review aims to provide new insights and ideas for advancing CRISPR/Cas9-based delivery strategies and to facilitate breakthroughs in biomedical research and therapeutic applications.

A Fault Diagnosis Strategy for Analog Circuits with Limited Samples Based on the Combination of the Transformer and Generative Models.

As a pivotal integral component within electronic systems, analog circuits are of paramount importance for the timely detection and precise diagnosis of their faults. However, the objective reality of limited fault samples in operational devices with analog circuitry poses challenges to the direct applicability of existing diagnostic methods. This study proposes an innovative approach for fault diagnosis in analog circuits by integrating deep convolutional generative adversarial networks (DCGANs) with the Transformer architecture, addressing the problem of insufficient fault samples affecting diagnostic performance. Firstly, the employment of the continuous wavelet transform in combination with Morlet wavelet basis functions serves as a means to derive time-frequency images, enhancing fault feature recognition while converting time-domain signals into time-frequency representations. Furthermore, the augmentation of datasets utilizing deep convolutional GANs is employed to generate synthetic time-frequency signals from existing fault data. The Transformer-based fault diagnosis model was trained using a mixture of original signals and generated signals, and the model was subsequently tested. Through experiments involving single and multiple fault scenarios in three simulated circuits, a comparative analysis of the proposed approach was conducted with a number of established benchmark methods, and its effectiveness in various scenarios was evaluated. In addition, the ability of the proposed fault diagnosis technique was investigated in the presence of limited fault data samples. The outcome reveals that the proposed diagnostic method exhibits a consistently high overall accuracy of over 96% in diverse test scenarios. Moreover, it delivers satisfactory performance even when real sample sizes are as small as 150 instances in various fault categories.

Cellular organelles as drug carriers for disease treatment.

Organelles not only constitute the basic structure of the cell but also are important in maintaining the normal physiological activities of the cell. With the development of biomimetic nanoscience, researchers have developed technologies to use organelles as drug carriers for disease treatment. Compared with traditional drug carriers, organelle drug carriers have the advantages of good biocompatibility, high drug loading efficiency, and modifiability, and the surface biomarkers of organelles can also participate in intracellular signal transduction to enhance intracellular and intercellular communication, and assist in enhancing the therapeutic effect of drugs. Among different types of organelles, extracellular vesicles, lipid droplets, lysosomes, and mitochondria have been used as drug carriers. This review briefly reviews the biogenesis, isolation methods, and drug-loading methods of four types of organelles, and systematically summarizes the research progress in using organelles as drug-delivery systems for disease treatment. Finally, the challenges faced by organelle-based drug delivery systems are discussed. Although the organelle-based drug delivery systems still face challenges before they can achieve clinical translation, they offer a new direction and vision for the development of next-generation drug carriers.

DNA-directed assembly of nanomaterials and their biomedical applications.

In the past decades, DNA has been widely used in the field of nanostructures due to its unique programmable properties. Besides being used to form its own diverse structures such as the assembly of DNA origami, DNA can also be used for the assembly of nanostructures with other materials. In this review, different strategies for the functionalization of DNA on nanoparticle surfaces are listed, and the roles of DNA in the assembly of nanostructures as well as the influencing factors are discussed. Finally, the biomedical applications of DNA-assembled nanostructures were summarized. This review provided new insight into the application of DNA in nanostructure assembly.

In situ stimulus-responsive self-assembled nanomaterials for drug delivery and disease treatment.

The individual motifs that respond to specific stimuli for the self-assembly of nanomaterials play important roles. In situ constructed nanomaterials are formed spontaneously without human intervention and have promising applications in bioscience. However, due to the complex physiological environment of the human body, designing stimulus-responsive self-assembled nanomaterials in vivo is a challenging problem for researchers. In this article, we discuss the self-assembly principles of various nanomaterials in response to the tissue microenvironment, cell membrane, and intracellular stimuli. We propose the applications and advantages of in situ self-assembly in drug delivery and disease diagnosis and treatment, with a focus on in situ self-assembly at the lesion site, especially in cancer. Additionally, we introduce the significance of introducing exogenous stimulation to construct self-assembly in vivo. Based on this foundation, we put forward the prospects and possible challenges in the field of in situ self-assembly. This review uncovers the relationship between the structure and properties of in situ self-assembled nanomaterials and provides new ideas for innovative drug molecular design and development to solve the problems in the targeted delivery and precision medicine.

DNA-Guided Metallization of Nanomaterials and Their Biomedical Applications.

Precise control of the structure of metallic nanomaterials is critical for the advancement of nanobiotechnology. As DNA (deoxyribonucleic acid) can readily modify various moieties, such as sulfhydryl, carboxyl, and amino groups, using DNA as a directing ligand to modulate the morphology of nanomaterials is a promising strategy. In this review, we focus on the use of DNA as a template to control the morphology of metallic nanoparticles and their biomedical applications, discuss the use of DNA for the metallization of gold and silver, explore the factors that influence the process, and outline its biomedical applications. This review aims to provide valuable insights into the DNA-guided growth of nanomaterials. The challenges and future directions are also discussed.

High Precision Feature Fast Extraction Strategy for Aircraft Attitude Sensor Fault Based on RepVGG and SENet Attention Mechanism.

The attitude sensor of the aircraft can give feedback on the perceived flight attitude information to the input of the flight controller to realize the closed-loop control of the flight attitude. Therefore, the fault diagnosis of attitude sensors is crucial for the flight safety of aircraft, in view of the situation that the existing diagnosis methods fail to give consideration to both the diagnosis rate and the diagnosis accuracy. In this paper, a fast and high-precision fault diagnosis strategy for aircraft sensor is proposed. Specifically, the aircraft's dynamics model and the attitude sensor's fault model are built. The SENet attention mechanism is used to allocate weights for the collected time-domain fault signals and transformed time-frequency signals, and then inject the fused feature signals with weights into the RepVGG based on the convolutional neural network structure for deep feature mining and classification. Experimental results show that the proposed method can achieve good precision speed tradeoff.

Effect of Yttrium on the Microstructure and Mechanical Properties of PH13-8Mo Stainless Steels Produced by Selective Laser Melting.

In the present work, PH13-8Mo stainless steel parts without yttrium and with yttrium (Y) were manufactured by selective laser melting (SLM). The microstructure, phase composition and grain orientation of the stainless steels parts with Y and without Y were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), electron-backscatter diffraction (EBSD), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM). The characterization results revealed that the addition of Y clearly refined the grain size of the PH13-8Mo steel formed part, resulting in more equiaxed massive grains and in a less anisotropic microstructure. PH13-8Mo stainless steel formed parts were mainly composed of martensite and retained austenite. The addition of Y could significantly increase the content of retained austenite and also generate nano-sized precipitates containing Y. The mechanical test results showed that both strength and toughness of the shaped parts containing Y were improved synergistically. The yield strength reached 1443 MPa, the elongation was 12.2%, and the room temperature impact energy reached 124.25 J/cm2. The strengthening and toughening by Y of the formed parts were mainly attributed to grain refinement, higher volume fraction of the retained austenite and the formation of nano-sized precipitates containing Y.

Multifunctional theranostic nanoplatform loaded with autophagy inhibitor for enhanced photothermal cancer therapy under mild near-infrared irradiation.

Photothermal therapy (PTT) usually causes hyperthermia and damages healthy tissues. Developing a PTT platform with enhanced therapeutic effects and reduced side effects to normal tissues attracts increasing attention. Herein, we developed a multifunctional theranostic nanoplatform using poly(lactic-co-glycolic acid) (PLGA) loaded with near-infrared (NIR) photothermal agent (new indocyanine green IR820), fluorescence imaging agent (ZnCdSe/ZnS quantum dots, QDs) and autophagy inhibitor (chloroquine, CQ). These PLGA/IR820/Fluorescence imaging agent/CQ co-loading nanoparticles (termed PIFC NPs) displayed photothermal effects, enhanced the stability of IR820 in vivo, and enabled QDs to have stable fluorescent signals in vitro and in vivo. The PIFC NPs with particle size around 240 nm aggregated to tumor sites through the high permeability and retention effects of solid tumors. The intracellular delivery of CQ molecules through PIFC NPs significantly attenuated the degradation of autophagic lysosomes in tumor cells and effectively inhibited the autophagy mediated repair of photothermal damaged cells. Under milder NIR irradiation conditions, PIFC NPs exhibited high antitumor effect. By regulating autophagy, PTT can be effectively sensitized, which will provide a new idea for future cancer treatment research.

Aptamer-based biosensors for virus protein detection.

Virus threatens life health seriously. The accurate early diagnosis of the virus is vital for clinical control and treatment of virus infection. Aptamers are small single-stranded oligonucleotides (DNAs or RNAs). In this review, we summarized aptasensors for virus detection in recent years according to the classification of the viral target protein, and illustrated common detection mechanisms in the aptasensors (colorimetry, fluorescence assay, surface plasmon resonance (SPR), surface-enhanced raman spectroscopy (SERS), electrochemical detection, and field-effect transistor (FET)). Furthermore, aptamers against different target proteins of viruses were summarized. The relationships between the different biomarkers of the viruses and the detection methods, and their performances were revealed. In addition, the challenges and future directions of aptasensors were discussed. This review will provide valuable references for constructing on-site aptasensors for detecting viruses, especially the SARS-CoV-2.

Catalyst-free reductive cyclization of bis(2-aminophenyl) disulfide with CO2 in the presence of BH3NH3 to synthesize 2-unsubstituted benzothiazole derivatives.

An efficient and catalyst-free methodology for the reductive cyclization of various disulfides using BH3NH3 as a reductant and CO2 as a C1 resource was developed. The desired 2-unsubstituted benzothiazole derivatives were obtained in good to excellent yields. Moreover, mechanism investigation demonstrated that BH3NH3 played an important role in the formation of benzothiazole. As a reducing agent, BH3NH3 reduced CO2 and cleaved the S-S bond of the disulfide efficiently. In addition, the N-H bond of the amino group was also activated by BH3NH3. To the best of our knowledge, this is an unprecedented catalyst-free protocol for the synthesis of 2-unsubstituted benzothiazole from bis(2-aminophenyl) disulfide and CO2.

Aptamer based probes for living cell intracellular molecules detection.

Biosensors have been employed for monitoring and imaging biological events and molecules. Sensitive detection of different biomolecules in vivo can reflect the changes of physiological conditions in real-time, which is of great significance for the diagnosis and treatment of diseases. The detection of intracellular molecules concentration change can indicate the occurrence and development of disease. But the analysis process of the existing detection methods, such as Western blot detection of intracellular protein, polymerase chain reaction (PCR) technique quantitative analysis of intracellular RNA and DNA, usually need to extract the cell lysis which is complex and time-consuming. Fluorescence bioimaging enables in situ monitoring of intracellular molecules in living cells. By combining the specificity of aptamer for intracellular molecules binding, and biocompatibility of fluorescent materials and nanomaterials, biosensors with different nanostructures have been developed to enter into living cells for analysis. This review summarizes the fluorescence detection methods based on aptamer for intracellular molecules detection. The principles, limit of detection, advantages, and disadvantages of different platforms for intracellular molecular fluorescent response are summarized and reviewed. Finally, the current challenges and future developments were discussed and proposed.

Yeast as carrier for drug delivery and vaccine construction.

Yeast has been employed as an effective derived drug carrier as a unicellular microorganism. Many research works have been devoted to the encapsulation of nucleic acid compounds, insoluble small molecule drugs, small molecules, liposomes, polymers, and various nanoparticles in yeast for the treatment of disease. Recombinant yeast-based vaccine carriers (WYV) have played a major role in the development of vaccines. Herein, the latest reports on the application of yeast carriers and the development of related research are summarized, a conceptual description of gastrointestinal absorption of yeast carriers, as well as the various package forms of different drug molecules and nanoparticles in yeast carriers are introduced. In addition, the advantages and development of recombinant yeast vaccine carriers for the disease, veterinary and aquaculture applications are discussed. Moreover, the current challenges and future directions of yeast carriers are proposed.

Photolytic Removal of Red Blood Cell Membranes Camouflaged on Nanoparticles for Enhanced Cellular Uptake and Combined Chemo-Photodynamic Inhibition of Cancer Cells.

Biomimetic therapeutics offer great potential for drug delivery that avoids immune recognition. However, the coated cell membrane usually hinders the cellular uptake of nanoparticles; thus, structure-changeable formulations have attracted increasing attention. Herein, we report photolytic pyropheophorbide a (PA)-inserted red blood cell (RBC) membrane-camouflaged curcumin dimeric prodrug (CUR2-TK)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles [(CUR2-TK)-PLGA@RBC-PA] for enhanced cancer therapy. In these nanoparticles, the inner core was constructed using PLGA and loaded with our synthesized reactive oxygen species (ROS)-responsive cleavable curcumin dimeric prodrug (CUR2-TK). The nanoparticles generated ROS in response to the light irradiation attributed to the incorporated PA. The ROS further triggered the lysis of the cell membrane and exposed the nanoparticles for enhanced tumor cellular uptake, and the ROS also cleaved CUR2-TK for controlled CUR drug release. Moreover, the ROS performed photodynamic therapy (PDT). The chemotherapy and PDT produced a combined effect in the treatment of cancer cells, thus enhancing anticancer therapeutic efficacy.

Effect of Organizational Evolution on the Stress Corrosion Cracking of the Cr-Co-Ni-Mo Series of Ultra-High Strength Stainless Steel.

Different microstructures were obtained under various thermal conditions by adjusting the heat treatment parameters of the Cr-Co-Ni-Mo series of ultra-high strength stainless steel. The effect of organizational evolution on the stress corrosion cracking (SCC) of the Cr-Co-Ni-Mo series of ultra-high strength stainless steel was investigated using potentiodynamic polarization curves, electrochemical impedance spectroscopy (EIS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and other test methods in combination with slow strain rate tensile tests (SSRTs). The results show that the Mo- and Cr-rich clusters and precipitation of the Laves phase reduce the corrosion resistance, while increasing the austenite content can improve the corrosion resistance. The Cr-Co-Ni-Mo series of ultra-high strength stainless steel has a high SCC resistance after quenching at 1080 °C and undergoing deep cooling (DC) treatment at -73 °C. With increasing holding time, the strength of the underaged and peak-aged specimens increases, but the passivation and SCC resistance decreases. At the overaged temperature, the specimen has good SCC resistance after a short holding time, which is attributed to its higher austenite content and lower dislocation density. As a stable hydrogen trap in steel, austenite effectively improves the SCC resistance of steel. However, under the coupled action of hydrogen and stress, martensitic transformation occurs due to the decrease in the lamination energy of austenite, and the weak martensitic interface becomes the preferred location for crack initiation and propagation.

Metal-Organic Frameworks for Bioimaging: Strategies and Challenges.

Metal-organic frameworks (MOFs), composited with metal ions and organic linkers, have become promising candidates in the biomedical field own to their unique properties, such as high surface area, pore-volume, tunable pore size, and versatile functionalities. In this review, we introduce and summarize the synthesis and characterization methods of MOFs, and their bioimaging applications, including optical bioimaging, magnetic resonance imaging (MRI), computed tomography (CT), and multi-mode. Furthermore, their bioimaging strategies, remaining challenges and future directions are discussed and proposed. This review provides valuable references for the designing of molecular bioimaging probes based on MOFs.

Robust adaptive recursive sliding mode attitude control for a quadrotor with unknown disturbances.

Model uncertainties, unknown disturbances, and sensors measurement noises affect the attitude tracking control performance of quadrotors. In this article, a novel robust adaptive recursive sliding mode control (ARSMC) strategy is proposed for the quadrotor to improve the attitude tracking performance and disturbance rejection. Firstly, recursive sliding mode control is introduced, including a two-layer sliding surface, an integral sliding surface, and a fast nonsingular terminal sliding surface, which are recursive. Both sliding surfaces converge to zero in turn. And the initial value of the integral sliding surface is designed to eliminate the reaching phase. Besides, the adaptive gain adjustment method is presented to make an estimate of the unknown upper bound of disturbances. It is proved that the attitude control system has the finite-time convergence and the attitude tracking error will converge to zero. A quadrotor attitude test platform is built to evaluate the proposed algorithm. For comparison, twisting controller (TC), cascade PID, and active disturbance rejection control (ADRC) algorithms are introduced. Ultimately, the efficiency and feasibility of the proposed algorithm are verified by simulation and experimental results.

Light responsive nucleic acid for biomedical application.

Nucleic acids are widely used in biomedical applications because of their programmability and biocompatibility. The light responsive nucleic acids have attracted wide attention due to their remote control and high spatiotemporal resolution. In this review, we summarized the latest developments in biomedicine of light responsive molecules. The molecules which confer light responsive properties to nucleic acids were summarized. The binding sites of molecules to nucleic acids, the induced structural changes, and functional regulation of nucleic acids were reviewed. Then, the biomedical applications of light responsive nucleic acids were listed, such as drug delivery, biosensing, optogenetics, gene editing, etc. Finally, the challenges were discussed and possible future directions of light-responsive nucleic acids were proposed.

Deoxyribonucleic acid anchored on cell membranes for biomedical application.

Engineering cellular membranes with functional molecules provides an attractive strategy to manipulate cellular behaviors and functionalities. Currently, synthetic deoxyribonucleic acid (DNA) has emerged as a promising molecular tool to engineer cellular membranes for biomedical applications due to its molecular recognition and programmable properties. In this review, we summarized the recent advances in anchoring DNA on the cellular membranes and their applications. The strategies for anchoring DNA on cell membranes were summarized. Then their applications, such as immune response activation, receptor oligomerization regulation, membrane structure mimicking, cell-surface biosensing, and construction of cell clusters, were listed. The DNA-enabled intelligent systems which were able to sense stimuli such as DNA strands, light, and metal ions were highlighted. Finally, insights regarding the remaining challenges and possible future directions were provided.