Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membrane-decorated nanoparticles.

Current cytotoxic T lymphocyte (CTL) activating immunotherapy requires a major histocompatibility complex I (MHC-I)-mediated presentation of tumor-associated antigens, which malfunctions in around half of patients with triple-negative breast cancer (TNBC). Here, we create a LCL161-loaded macrophage membrane decorated nanoparticle (LMN) for immunotherapy of MHC-I-deficient TNBC. SIRPα on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161, which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer cells. The released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 folds. LMNs also block CD47-mediated phagocytosis suppression. LMNs inhibit the growth of MHC-I-deficient TNBC tumors, as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel, and prolong the survival of animals, during which process CTLs also play important roles. This macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophage-mediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

Chemical conjugation mitigates immunotoxicity of chemotherapy via reducing receptor-mediated drug leakage from lipid nanoparticles.

Immunotoxicity remains a major hindrance to chemotherapy in cancer therapy. Nanocarriers may alleviate the immunotoxicity, but the optimal design remains unclear. Here, we created two variants of maytansine (DM1)-loaded synthetic high-density lipoproteins (D-sHDL) with either physically entrapped (ED-sHDL) or chemically conjugated (CD-sHDL) DM1. We found that CD-sHDL showed less accumulation in the tumor draining lymph nodes (DLNs) and femur, resulting in a lower toxicity against myeloid cells than ED-sHDL via avoiding scavenger receptor class B type 1 (SR-B1)-mediated DM1 transportation into the granulocyte-monocyte progenitors and dendritic cells. Therefore, higher densities of lymphocytes in the tumors, DLNs, and blood were recorded in mice receiving CD-sHDL, leading to a better efficacy and immune memory of CD-sHDL against colon cancer. Furthermore, liposomes with conjugated DM1 (CD-Lipo) showed lower immunotoxicity than those with entrapped drug (ED-Lipo) through the same mechanism after apolipoprotein opsonization. Our findings highlight the critical role of drug loading patterns in dictating the biological fate and activity of nanomedicine.

A decade of insight: bibliometric analysis of gut microbiota's role in osteoporosis (2014-2024).

Purpose: Osteoporosis represents a profound challenge to public health, underscoring the critical need to dissect its complex etiology and identify viable targets for intervention. Within this context, the gut microbiota has emerged as a focal point of research due to its profound influence on bone metabolism. Despite this growing interest, the literature has yet to see a bibliometric study addressing the gut microbiota's contribution to both the development and management of osteoporosis. This study aims to fill this gap through an exhaustive bibliometric analysis. Our objective is to uncover current research hotspots, delineate key themes, and identify future research trends. In doing so, we hope to provide direction for future studies and the development of innovative treatment methods. Methods: Relevant publications in this field were retrieved from the Web of Science Core Collection database. We used VOSviewer, CiteSpace, an online analysis platform and the R package "Bibliometrix" for bibliometric analysis. Results: A total of 529 publications (including 351 articles and 178 reviews) from 61 countries, 881 institutions, were included in this study. China leads in publication volume and boast the highest cumulative citation. Shanghai Jiao Tong University and Southern Medical University are the leading research institutions in this field. Nutrients contributed the largest number of articles, and J Bone Miner Res is the most co-cited journal. Of the 3,166 scholars who participated in the study, Ohlsson C had the largest number of articles. Li YJ is the most co-cited author. "Probiotics" and "inflammation" are the keywords in the research. Conclusion: This is the first bibliometric analysis of gut microbiota in osteoporosis. We explored current research status in recent years and identified frontiers and hot spots in this research field. We investigate the impact of gut microbiome dysregulation and its associated inflammation on OP progression, a topic that has garnered international research interest in recent years. Additionally, our study delves into the potential of fecal microbiota transplantation or specific dietary interventions as promising avenues for future research, which can provide reference for the researchers who focus on this research filed.

Prevalence and trends of Chlamydia trachomatis infection in female sex workers and men who have sex with men in China: a systematic review and meta-analysis.

INTRODUCTION: Chlamydia trachomatis infection can cause a significant disease burden in high-risk populations. This study aimed to assess the overall prevalence of C. trachomatis infection, and determine the long-term trends and geographic distribution of this infection among female sex workers (FSWs) and men who have sex with men (MSM) in China. METHODS: The PubMed, Web of Science, CNKI, Wanfang Data and VIP databases were searched from 1 January 1990 through 30 April 2023. Publications in which C. trachomatis infection was detected using nucleic acid amplification tests (NAATs) were included. The Q test and I2 statistics were used to assess the heterogeneity between studies. A random-effect model was used to estimate the pooled prevalence of C. trachomatis infection. Subgroup, meta-regression, and sensitivity analyses were performed to explore the sources of heterogeneity. Publication bias was evaluated using Egger's test. Trend analysis of the prevalence was performed using the Jonckheere-Terpstra trend test method. RESULTS: Sixty-one studies were eligible for inclusion (including 38 for FSWs and 23 for MSM). The pooled prevalence of C. trachomatis infection was 19.5% (95% CI: 16.4, 23.0) among FSWs and 12.7% (95% CI: 9.2, 17.7) in the rectum, 6.4% (95% CI: 5.3, 7.8) in the urethra and 1.3% (95% CI: 0.8, 2.1) in the oropharynx from MSM in China. The subgroup analyses showed that the sample size, study period, study region, specimen collection type, molecular diagnosis method, and recruitment site could explain some heterogeneity among studies of FSWs, and the publication language, study period, study region, molecular diagnosis method, and specimen collection anatomical site could explain some heterogeneity among studies of MSM. From 1998 to 2004, 2005 to 2009, 2010 to 2015, and 2016 to 2021, the pooled prevalence of C. trachomatis infection among FSWs were 30.3%, 19.9%, 21.4%, and 11.3%, respectively. For MSM, the pooled prevalence from 2003 to 2009, 2010 to 2015, and 2016 to 2022 were 7.8%, 4.7%, and 6.5%, respectively. However, no overall decline in the prevalence of C. trachomatis infection was observed among FSWs (z = -1.51, P = 0.13) or MSM (z = -0.71, P = 0.48) in China. CONCLUSIONS: The prevalence of C. trachomatis infection was high in these two high-risk populations in China. The findings of this study provide evidence for the formulation of effective surveillance and screening strategies for the prevention and control of C. trachomatis infection among these two specific populations.

Ultrasensitive and Wash-Free Detection of Tumor Extracellular Vesicles by Aptamer-Proximity-Ligation-Activated Rolling Circle Amplification Coupled to Single Particle ICP-MS.

Tumor-derived extracellular vesicles (TEVs) are rich in cellular information and hold great promise as a biomarker for noninvasive cancer diagnosis. However, accurate measurement of TEVs presents challenges due to their low abundance and potential interference from a high number of EVs derived from normal cells. Herein, an aptamer-proximity-ligation-activated rolling circle amplification (RCA) method for EV membrane recognition, coupled with single particle inductively coupled plasma mass spectrometry (sp-ICP-MS) for the quantification of TEVs, is developed. When DNA-labeled ultrasmall gold nanoparticle (AuNP) probes bind to the long chains formed by RCA, they aggregate to form large particles. Notably, small AuNPs scarcely produce pulse signals in sp-ICP-MS, thereby detecting TEVs in a wash-free manner. By leveraging the strong binding affinity of aptamers, dual aptamers for EpCAM and PD-L1 recognition, and the sp-ICP-MS technique, this method offers remarkable sensitivity and selectivity in tracing TEVs. Under optimized conditions, the present method shows a favorable linear relationship between the pulse signal frequency of sp-ICP-MS and TEV concentration within the range of 105-107 particles/mL, along with a detection limit of 1.1 × 104 particles/mL. The pulse signals from sp-ICP-MS combined with machine learning algorithms are used to discriminate cancer patients from healthy donors with 100% accuracy. Due to its simple and fast operation and excellent sensitivity and accuracy, this approach holds significant potential for diverse applications in life sciences and personalized medicine.

Pullulan-Based Spray-Dried Mucoadhesive Microparticles for Sustained Oromucosal Drug Delivery.

Mucoadhesive microparticles for oromucosal drug delivery offer several advantages, including intimate contact with the mucosa, delivery to less accessible regions, extended residence time, sustained drug release, reduced irritation, and improved patient compliance. In this study, pullulan was used to prepare mucoadhesive spray-dried microparticles for delivering benzydamine hydrochloride (BZH) to oral mucosa. The BZH-pullulan spray-dried microparticles had a mean size of <25 µm with an angle of repose values between 25.8-36.6°. Pullulan markedly extended drug-release time to >180 min, ~9 times greater than the duration (i.e., 20 min) reportedly achieved by chitosan. Kinetic analysis showed the drug-release rate was concentration dependent and jointly controlled by drug diffusion and polymer chain relaxation. Further, pullulan was mucoadhesive and was able to retain up to 78.8% w/w of microencapsulated gold nanoparticle probes at the mucosal membrane. These data strongly suggest that BZH-pullulan microparticles have great potential for oromucosal drug delivery, by providing elongated residence time in situ and sustained drug release for the treatment of local diseases.

Deep Learning Promotes Profiling of Multiple miRNAs in Single Extracellular Vesicles for Cancer Diagnosis.

Extracellular vesicle microRNAs (EV miRNAs) are critical noninvasive biomarkers for early cancer diagnosis. However, accurate cancer diagnosis based on bulk analysis is hindered by the heterogeneity among EVs. Herein, we report an approach for profiling single-EV multi-miRNA signatures by combining total internal reflection fluorescence (TIRF) imaging with a deep learning (DL) algorithm for the first time. This innovative technique allows for the precise characterization of EV miRNAs at the single-vesicle level, overcoming the challenges posed by EV heterogeneity. TIRF with high resolution and a signal-to-noise ratio can simultaneously detect multi-miRNAs in situ in individual EVs. DL algorithm avoids complicated and inaccurate artificial feature extraction, achieving automated high-resolution image analysis. Using this approach, we reveal that the main variation of EVs from 5 cancer cells and normal plasma is the triple-positive EV subpopulation, and the classification accuracy of single triple-positive EVs from 6 sources can reach above 95%. In the clinical cohort, 20 patients (5 lung cancer, 5 breast cancer, 5 cervical cancer, and 5 colon cancer) and 5 healthy controls are predicted with an overall accuracy of 100%. This single-EV strategy provides new opportunities for exploring more specific EV biomarkers to achieve cancer diagnosis and classification.

Preparation of nitrogen doped hyper-crosslinked polymer-based hard carbon for high performance Li+/Na+ battery anode.

Hyper cross-linked polymers (HCPs), as a key precursor of hard carbon (HC) anode materials, stand out because of their capacity for molecular-scale structural design and comparatively straightforward preparation techniques, which are not seen in other porous materials synthesized procedure. A novel synthesis method of HCPs is developed in this paper, which is through the incorporation of functional macromolecules, the structural control and heteroatom doping of the product has been achieved, thus augmenting its electrochemical performance in batteries. In this work, carbonized tetraphenylporphyrin zinc (TPP-Zn) doped HCP-based hard carbon (CTHCP) with stable structure was prepared by Friedel-Crafts reaction and carbonization by using naphthalene and trace TPP-Zn as monomers, dimethoxybenzene (DMB) as crosslinking agent and FeCl3 as catalyst. The introduction of TPP-Zn, a functional macromolecule with unique two-dimensional structure, realized the pore structure regulation and N doping of the raw carbonized HCP-based hard carbon (CHCP). The results showed that CTHCP had higher mesoporous volume, N content and wider layer spacing than CHCP. In addition, CTHCP anode exhibited excellent Li+/Na+ storage performance, initial reversible capacity, rate performance and long cycle life. More amount of N-containing (N-5) active sites and mesoporous content in CTHCP anode was the main reason for the improvement of Na+ storage effect. While the increased interlayer spacing had a greater effect on the lithium storage capacity. This study uncovered the design rules of HC anode materials suitable for Li+/Na+ batteries and provided a new idea for the preparation of high-performance HC anode materials.

Adenosine-modulating synthetic high-density lipoprotein for chemoimmunotherapy of triple-negative breast cancer.

Adenosine (ADO) is a common chemotherapy-associated immune checkpoint that hinders anti-tumor immunity-mediated efficacy of chemotherapy. Herein, we created a synthetic high-density lipoprotein (sHDL) by co-assembly of a doxorubicin (DOX)-apolipoprotein A1 mimetic peptide conjugate, PSB-603 (an A2BR inhibitor), phospholipid, and cholesterol oleate with a microfluidic-based method. The obtained DP-sHDL showed a self-promoted drug delivery to cancer cells via remodeling tumor microenvironment. DP-sHDL could trigger the release of ATP from cancer cells and inhibit its conversion into ADO. Consequently, DP-sHDL, while increasing immunogenic cell death, reduced intratumoral ADO levels by 58%. This treatment improved both the density and activity of CD8+ T cells as well as NK cells and relieved the immunosuppressive microenvironment, and led to a substantial inhibition of 4T1 tumor growth, thereby extending the survival of mice. The efficacy of DP-sHDL could be further improved when used in combination with immune checkpoint blockade therapy. We envision that this platform provides a simple yet promising strategy to enhance anti-tumor response of chemotherapy by relieving treatment-associated immunosuppression.

Is state-owned enterprise merging private enterprise "market choice" or "space crowding" ? -Based on the motives of equity transfer of mixed-ownership enterprises.

Many state-owned enterprises have mergers and acquisitions (M&A) with private enterprises, which has caused private enterprises to worry about their living space being squeezed. Based on 572 data records about equity transfers of Chinese listed companies extracted from CSMAR4.0 from 2013 to 2020, this paper categorized ownership structures into three categories: privatization of state-owned enterprises (Category 1), state-owned enterprises merging private enterprises (Category 2), and state-owned enterprises merging state-owned enterprises (Category 3). The categorical regression of ex-ante equity transfer motivation revealed that the motives for Category 1 conformed to the phenomenon of the "pretty girl gets married first" and "embezzlement view." Category In contrast, the motives for Category 2 conformed to the "fiscal revenue view." The categorical regression of ex-post equity transfer motivation showed that all three types significantly improved various efficiencies and represented an optimal allocation of resources. Moreover, it was revealed that the transfer of equity to state-owned enterprises by inefficient private firms in Category 2 also significantly improved enterprise efficiency. Thus, it can be considered as a rational behavior of market selection and never squeezed the space crowding. Further analysis showed that the efficiency improvement is due to the symbiotic development relationship rather than the antagonistic relationship between heterogeneous shareholders. Therefore, it is suggested to initiate market-oriented reform by actively developing ownership mixed-ownership economy and adhering to the "two unwavering" basic economic system.

Retrolaminar migration as a complication of intraocular silicone oil injection detected on unenhanced CT.

AIM: To describe the clinical and radiologic features of retrolaminar migration silicone oil (SiO) and observe the dynamic position of ventricular oil accumulation in supine and prone. METHODS: For this retrospective study, 29 patients who had a history of SiO injection treatment and underwent unenhanced head computed tomography (CT) were included from January 2019 to October 2022. The patients were divided into migration-positive and negative groups. Clinical history and CT features were compared using Whitney U and Fisher's exact tests. The dynamic position of SiO was observed within the ventricular system in supine and prone. CT images were visually assessed for SiO migration along the retrolaminar involving pathways for vision (optic nerve, chiasm, and tract) and ventricular system. RESULTS: Intraocular SiO migration was found in 5 of the 29 patients (17.24%), with SiO at the optic nerve head (n=1), optic nerve (n=4), optic chiasm (n=1), optic tract (n=1), and within lateral ventricles (n=1). The time interval between SiO injection and CT examination of migration-positive cases was significantly higher than that of migration-negative patients (22.8±16.5mo vs 13.1±2.6mo, P<0.001). The hyperdense lesion located in the frontal horns of the right lateral ventricle migrated to the fourth ventricle when changing the position from supine to prone. CONCLUSION: Although SiO retrolaminar migration is unusual, the clinician and radiologist should be aware of migration routes. The supine combined with prone examination is the first-choice method to confirm the presence of SiO in the ventricular system.

Hounsfield units on abdominal computed tomography: a new tool for predicting osteoporosis.

BACKGROUND: Osteoporosis can cause bone fractures and disability, but early diagnosis faces challenges. Our proposed diagnostic indicators offer a new approach for early detection, which benefits early identification. PURPOSE: To determine the most appropriate threshold for predicting osteoporosis in patients with each section of vertebral body. MATERIAL AND METHODS: A retrospective analysis of 210 patients, including 646 vertebrae, who had both abdominal computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) within six months. The correlation between DXA T-score and CT Hounsfield units (HU) values was tested by Pearson. The area under the curve (AUC) was calculated using the threshold obtained from the regression equation. RESULTS: The thresholds matching the T-score of -2.5 were 85, 95, 85, and 90 HU for the upper axial plane of the vertebral body (Lau), the middle axial plane of the vertebral body (Lam), the lower axial plane of the vertebral body (Lad), and the mid-sagittal plane of the vertebral body (Lsm), respectively. Defining osteoporosis using CT as Lau ≤ 85, Lam ≤ 95, Lad ≤ 85, or Lsm ≤ 90 HU had a specificity of 88.1% (116/134) and sensitivity of 90.8% (69/76) for distinguishing DXA osteoporosis of the lumbar spine in 210 patients. T-score ≤-2.5 defined as Lau ≤85 or Lam ≤95 or Lad ≤85 or Lsm ≤90 HU had a specificity of 85.9% (275/320) and sensitivity of 82.8% (270/326) for DXA T-score ≤-2.5 in 646 lumbar vertebrae. CONCLUSION: CT HU values obtained based on different sections of the vertebral body in abdominal CT can be used as a supplementary measure to assess osteoporosis.

Tunable non-volatile memories based on 2D InSe/h-BN/GaSe heterostructures towards potential multifunctionality.

Floating-gate memories based on two-dimensional van der Waal (2D vdW) heterostructures play an important role in the development of next-generation information technology. The diversity of 2D vdW materials and their heterostructures provides flexibility in the design of novel storage architectures. However, 2D InSe/h-BN/GaSe heterostructures are rarely reported in the field of tunable non-volatile memories, probably due to the quality limitation of materials and complex interfaces from stackings. Herein, a floating-gate 2D InSe/h-BN/GaSe memory with high performance and atmosphere stability is demonstrated. It exhibits both a large ON/OFF current ratio of ∼105 and a good extinction ratio of ∼103, with an estimated maximum storage capacity of 5.1 × 1012 cm-2. Moreover, the storage performance can be regulated by optimizing the thickness of the insulating h-BN layer. Different device configurations have been explored to validate the working mechanism. Furthermore, a simulation of biological synaptic behavior is achieved on the same prototype device. The enhanced non-volatile characteristics enable the exploration of the integrated 2D memory and potential multifunctionality.

Study of the Microstructure of Coal at Different Temperatures and Quantitative Fractal Characterization.

In order to understand the influence of underground coal fires on coal fractures and pores, mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM) are combined to study the development of coal pore and fracture under high-temperature treatment and calculate the fractal dimension to analyze the relationship between the development of coal pore and fracture and the fractal dimension. The results show that the volume of pores and fractures of the coal sample (C200) treated at 200 °C (0.1715 mL/g) is greater than that of the coal sample (C400) treated at 400 °C (0.1209 mL/g), and both are greater than the original coal sample (RC) (0.1135 mL/g). The volume increase is mainly due to mesopores and macropores, and the proportions of mesopores and macropores in C200 were 70.15 and 59.97% in C400. The MIP fractal dimension shows a decreasing trend with the increase of temperature, and the connectivity of coal samples improved with the increase of temperature. The changes in volume and three-dimensional fractal dimension of C200 and C400 showed the opposite trend and are related to the different stress of coal matrix at different temperatures. The experimental SEM images confirm that the connectivity of coal fractures and pores improves with the increase of temperature. Based on the SEM experiment, the larger the fractal dimension, the more complex the surface is. The SEM surface fractal dimensions indicate that the surface fractal dimension of C200 is the smallest and that of C400 is the largest, which is consistent with the observations made by SEM. The combination of the two fractal dimensions is used to characterize the self-similarity of coal using the fractal dimension difference. When the temperature increased to 200 °C, the unordered expansion of the coal sample resulted in the largest fractal dimension difference and the lowest self-similarity. When heated to 400 °C, the fractal dimension difference of the coal sample is the smallest, and the microstructure of coal shows a regular groove-like development.

Design of public cultural sign based on Faster-R-CNN and its application in urban visual communication.

People are increasingly enthusiastic about pursuing spiritual life as economic and social development continues. Consequently, public cultural content has emerged as a pivotal instrument for promoting international soft power across diverse nations and regions. In today's era of advanced artificial intelligence, cultural sign design optimization has become achievable through its deployment. This article establishes an automatic layout optimization framework, specifically tailored to meet the visual communication requirements of public cultural signage. Our framework employs Faster-R-CNN for detecting and extracting key elements of the poster, yielding an impressive average detection accuracy of 94.6%. Subsequently, we use the three-division method in design to optimize the layout, ensuring that cultural logo design conforms to visual communication principles. Our framework produced an average cultural logo satisfaction rating exceeding 70% in actual tests, providing novel insights for cultural sign design within the artificial intelligence context and significantly enhancing the efficacy of visual communication conveyed through such signage.

Application of visual communication in digital animation advertising design using convolutional neural networks and big data.

In the age of big data, visual communication has emerged as a critical means of engaging with customers. Among multiple modes of visual communication, digital animation advertising is an exceptionally potent tool. Advertisers can create lively and compelling ads by harnessing the power of digital animation technology. This article proposes a multimodal visual communication system (MVCS) model based on multimodal video emotion analysis. This model automatically adjusts video content and playback mode according to users' emotions and interests, achieving more personalized video communication. The MVCS model analyses videos from multiple dimensions, such as vision, sound, and text, by training on a large-scale video dataset. We employ convolutional neural networks to extract the visual features of videos, while the audio and text features are extracted and analyzed for emotions using recurrent neural networks. By integrating feature information, the MVCS model can dynamically adjust the video's playback mode based on users' emotions and interaction behaviours, which increases its playback volume. We conducted a satisfaction survey on 106 digitally corrected ads created using the MVCS method to evaluate our approach's effectiveness. Results showed that 92.6% of users expressed satisfaction with the adjusted ads, indicating the MVCS model's efficacy in enhancing digital ad design effectiveness.

Gemcitabine-loaded synthetic high-density lipoprotein preferentially eradicates hepatic monocyte-derived macrophages in mouse liver with colorectal cancer metastases.

Liver metastasis of colorectal cancer (CRC) is the critical cause of CRC-related death due to its unique immunosuppressive microenvironment. In this study we generated a gemcitabine-loaded synthetic high-density lipoprotein (G-sHDL) to reverse immunosuppression in livers with CRC metastases. After intravenous injection, sHDL targeted hepatic monocyte-derived alternatively activated macrophages (Mono-M2) in the livers of mice bearing both subcutaneous tumors and liver metastases. The G-sHDL preferentially eradicated Mono-M2 in the livers with CRC metastases, which consequently prevented Mono-M2-mediated killing of tumor antigen-specific CD8+ T cells in the livers and thus improved the densities of tumor antigen-specific CD8+ T cells in the blood, tumor-draining lymph nodes and subcutaneous tumors of the treated mice. While reversing the immunosuppressive microenvironment, G-sHDL also induced immunogenic cell death of cancer cells, promoted maturation of dendritic cells, and increased tumor infiltration and activity of CD8+ T cells. Collectively, G-sHDL inhibited the growth of both subcutaneous tumors and liver metastases, and prolonged the survival of animals, which could be further improved when used in conjunction with anti-PD-L1 antibody. This platform can be a generalizable platform to modulate immune microenvironment of diseased livers.

A machine learning-based colorimetric sensor array for high-precision pathogen identification in household refrigerators.

A precise and convenient sensor was constructed to identify pathogens in household refrigerators (4 °C, RH = 55%) by integrating a volatile organic compound fingerprint-responsive gel-based colorimetric sensor array and a neural network. The platform is expected to be extended to the intelligent food packaging field and has promise for point-of-need monitoring of pathogens.

Rapid and Accurate Identification of Cell Phenotypes of Different Drug Mechanisms by Using Single-Cell Fluorescence Images Via Deep Learning.

Identification of a drug mechanism is vital for drug development. However, it often resorts to the expensive and cumbersome omics methods along with complex data analysis. Herein, we developed a methodology to analyze organelle staining images of single cells using a deep learning algorithm (TL-ResNet50) for rapid and accurate identification of different drug mechanisms. Based on the organelle-related cell morphological changes caused by drug action, the constructed deep learning model can fast predict the drug mechanism with a high accuracy of 92%. Further analysis reveals that drug combination at different ratios can enhance a certain mechanism or generate a new mechanism. This work would highly facilitate clinical medication and drug screening.

Ultrafast Microfluidic PCR Thermocycler for Nucleic Acid Amplification.

The polymerase chain reaction (PCR) is essential in nucleic acid amplification tests and is widely used in many applications such as infectious disease detection, tumor screening, and food safety testing; however, most PCR devices have inefficient heating and cooling ramp rates for the solution, which significantly limit their application in special scenarios such as hospital emergencies, airports, and customs. Here, we propose a temperature control strategy to significantly increase the ramp rates for the solution temperature by switching microfluidic chips between multiple temperature zones and excessively increasing the temperature difference between temperature zones and the solution; accordingly, we have designed an ultrafast thermocycler. The results showed that the ramp rates of the solution temperature are a linear function of temperature differences within a range, and a larger temperature difference would result in faster ramp rates. The maximum heating and cooling ramp rates of the 25 µL solution reached 24.12 °C/s and 25.28 °C/s, respectively, and the average ramp rate was 13.33 °C/s, 6-8 times higher than that of conventional commercial PCR devices. The thermocycler achieved 9 min (1 min pre-denaturation + 45 PCR cycles) ultrafast nucleic acid amplification, shortening the time by 92% compared to the conventional 120 min nucleic acid amplification, and has the potential to be used for rapid nucleic acid detection.