SBFI26 induces triple-negative breast cancer cells ferroptosis via lipid peroxidation.

SBFI26, an inhibitor of FABP5, has been shown to suppress the proliferation and metastasis of tumour cells. However, the underlying mechanism by which SBFI26 induces ferroptosis in breast cancer cells remains largely unknown. Three breast cancer cell lines were treated with SBFI26 and CCK-8 assessed cytotoxicity. Transcriptome was performed on the Illumina platform and verified by qPCR. Western blot evaluated protein levels. Malondialdehyde (MDA), total superoxide dismutase (T-SOD), Fe, glutathione (GSH) and oxidized glutathione (GSSG) were measured. SBFI26 induced cell death time- and dose-dependent, with a more significant inhibitory effect on MDA-MB-231 cells. Fer-1, GSH and Vitamin C attenuated the effects but not erastin. RNA-Seq analysis revealed that SBFI26 treatment significantly enriched differentially expressed genes related to ferroptosis. Furthermore, SBFI26 increased intracellular MDA, iron ion, and GSSG levels while decreasing T-SOD, total glutathione (T-GSH), and GSH levels.SBFI26 dose-dependently up-regulates the expression of HMOX1 and ALOX12 at both gene and protein levels, promoting ferroptosis. Similarly, it significantly increases the expression of SAT1, ALOX5, ALOX15, ALOXE3 and CHAC1 that, promoting ferroptosis while downregulating the NFE2L2 gene and protein that inhibit ferroptosis. SBFI26 leads to cellular accumulation of fatty acids, which triggers excess ferrous ions and subsequent lipid peroxidation for inducing ferroptosis.

Selection signatures and landscape genomics analysis to reveal climate adaptation of goat breeds.

Goats have achieved global prominence as essential livestock since their initial domestication, primarily owing to their remarkable adaptability to diverse environmental and production systems. Differential selection pressures influenced by climate have led to variations in their physical attributes, leaving genetic imprints within the genomes of goat breeds raised in diverse agroecological settings. In light of this, our study pursued a comprehensive analysis, merging environmental data with single nucleotide polymorphism (SNP) variations, to unearth indications of selection shaped by climate-mediated forces in goats. Through the examination of 43,300 SNPs from 51 indigenous goat breeds adapting to different climatic conditions using four analytical methods: latent factor mixed models (LFMM), F-statistics (Fst), Extended haplotype homozygosity across populations (XPEHH), and spatial analysis method (SAM), A total of 74 genes were revealed to display clear signs of selection, which are believed to be influenced by climatic conditions. Among these genes, 32 were consistently identified by at least two of the applied methods, and three genes (DENND1A, PLCB1, and ITPR2) were confirmed by all four approaches. Moreover, our investigation yielded 148 Gene Ontology (GO) terms based on these 74 genes, underlining pivotal biological pathways crucial for environmental adaptation. These pathways encompass functions like vascular smooth muscle contraction, cellular response to heat, GTPase regulator activity, rhythmic processes, and responses to temperature stimuli. Of significance, GO terms about endocrine regulation and energy metabolic responses, key for local adaptation were also uncovered, including biological processes, such as cell differentiation, regulation of peptide hormone secretion, and lipid metabolism. These findings contribute to our knowledge of the genetic structure of climate-triggered adaptation across the goat genome and have practical implications for marker-assisted breeding in goats.

Association between being large for gestational age and cardiovascular metabolic health in children conceived from assisted reproductive technology: a prospective cohort study.

BACKGROUND: To the best of our knowledge, no study has investigated the potential joint effect of large for gestational age (LGA) and assisted reproductive technology (ART) on the long-term health of children. METHODS: This was a prospective cohort study that recruited children whose parents had received ART treatment in the Center for Reproductive Medicine, Shandong Provincial Hospital, affiliated to Shandong University, between January 2006 and December 2017. Linear mixed model was used to compare the main outcomes. The mediation model was used to evaluate the intermediary effect of body mass index (BMI). RESULTS: 4138 (29.5%) children born LGA and 9910 (70.5%) children born appropriate for gestational age (AGA) were included in the present study. The offspring ranged from 0.4 to 9.9 years. LGAs conceived through ART were shown to have higher BMI, blood pressure, fasting blood glucose, fasting insulin, and homeostatic model assessment of insulin resistance values, even after controlling for all covariates. The odds of overweight and insulin resistance are also higher in LGA subjects. After adjusting for all covariates, LGAs conceived through ART had BMI and BMI z-scores that were 0.48 kg/m2 and 0.34 units greater than those of AGAs, respectively. The effect of LGA on BMI was identified as early as infancy and remained consistently significant throughout pre-puberty. CONCLUSIONS: Compared to AGA, LGA children conceived from ART were associated with increased cardiovascular-metabolic events, which appeared as early as infancy and with no recovery by pre-puberty.

Effects of chronic exposure to a high fat diet, nutritive or non-nutritive sweeteners on hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes of male Sprague-Dawley rats.

PURPOSE: Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions. METHODS: Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR. RESULTS: All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered. CONCLUSION: Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes.

Bioinspired Selenium-Nitrogen Exchange (SeNEx) Click Chemistry Suitable for Nanomole-Scale Medicinal Chemistry and Bioconjugation.

Click chemistry is a powerful molecular assembly strategy for rapid functional discovery. The development of click reactions with new connecting linkage is of great importance for expanding the click chemistry toolbox. We report the first selenium-nitrogen exchange (SeNEx) click reaction between benzoselenazolones and terminal alkynes (Se-N to Se-C), which is inspired by the biochemical SeNEx between Ebselen and cysteine (Cys) residue (Se-N to Se-S). The formed selenoalkyne connection is readily elaborated, thus endowing this chemistry with multidimensional molecular diversity. Besides, this reaction is modular, predictable, and high-yielding, features fast kinetics (k2≥14.43 M-1 s-1), excellent functional group compatibility, and works well at miniaturization (nanomole-scale), opening up many interesting opportunities for organo-Se synthesis and bioconjugation, as exemplified by sequential click chemistry (coupled with ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) and sulfur-fluoride exchange (SuFEx)), selenomacrocycle synthesis, nanomole-scale synthesis of Se-containing natural product library and DNA-encoded library (DEL), late-stage peptide modification and ligation, and multiple functionalization of proteins. These results indicated that SeNEx is a useful strategy for new click chemistry developments, and the established SeNEx chemistry will serve as a transformative platform in multidisciplinary fields such as synthetic chemistry, material science, chemical biology, medical chemistry, and drug discovery.

Inhibition of MiR-106b-5p mediated by exosomes mitigates acute kidney injury by modulating transmissible endoplasmic reticulum stress and M1 macrophage polarization.

Acute kidney injury (AKI), mainly caused by Ischemia/reperfusion injury (IRI), is a common and severe life-threatening disease with high mortality. Accumulating evidence suggested a direct relationship between endoplasmic reticulum (ER) stress response and AKI progression. However, the role of the transmissible ER stress response, a new modulator of cell-to-cell communication, in influencing intercellular communication between renal tubular epithelial cells (TECs) and macrophages in the AKI microenvironment remains to be determined. To address this issue, we first demonstrate that TECs undergoing ER stress are able to transmit ER stress to macrophages via exosomes, promoting macrophage polarization towards the pro-inflammatory M1 phenotype in vitro and in vivo. Besides, the miR-106b-5p/ATL3 signalling axis plays a pivotal role in the transmission of ER stress in the intercellular crosstalk between TECs and macrophages. We observed an apparent increase in the expression of miR-106b-5p in ER-stressed TECs. Furthermore, we confirmed that ALT3 is a potential target protein of miR-106b-5p. Notably, the inhibition of miR-106b-5p expression in macrophages not only restores ATL3 protein level but also decreases transmissible ER stress and hinders M1 polarization, thus alleviating AKI progression. Additionally, our results suggest that the level of exosomal miR-106b-5p in urine is closely correlated with the severity of AKI patients. Taken together, our study sheds new light on the crucial role of transmissible ER stress in the treatment of AKI through the regulation of the miR-106b-5p/ATL3 axis, offering new ideas for treating AKI.

Enolate-Azide [3 + 2]-Cycloaddition Reaction Suitable for DNA-Encoded Library Synthesis.

The DNA-encoded chemical library (DEL) is a powerful hit selection technique in either basic science or innovative drug discovery. With the aim to circumvent the issue concerning DNA barcode damage in a conventional on-DNA copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC), we have successfully developed the first DNA-compatible enolate-azide [3 + 2] cycloaddition reaction. The merits of this DEL chemistry include metal-free reaction and high DNA fidelity, high conversions and easy operation, broad substrate scope, and ready access to the highly substituted 1,4,5-trisubstituted triazoles. Thus, it will not only further enrich the DEL chemistry toolbox but also will have great potential in practical DEL synthesis.

Plasmopara viticola RxLR effector PvAvh77 triggers cell death and governs immunity responses in grapevine.

Grapevine downy mildew, caused by the oomycete Plasmopara viticola, is one of the most significant production challenges for the grape and wine industry. P. viticola injects a plethora of effectors into its host cells to disrupt immune processes, but the mechanisms by which these effectors act at the molecular level have not been well characterized. Herein, we show that a candidate P. viticola avirulence homolog (Avh) RxLR effector gene, designated PvAvh77, was strongly up-regulated during the initial stages of P. viticola infection in Vitis vinifera. Further experiments demonstrated that PvAvh77 could trigger non-specific cell death when expressed in the wild grapevine Vitis riparia and in tobacco (Nicotiana benthamiana and Nicotiana tabacum). In addition, a truncated form of PvAvh77, designated PvAvh77-M2, was more active in inducing cell death in N. benthamiana and V. riparia than full-length PvAvh77. Ectopic expression of PvAvh77 in V. vinifera 'Thompson Seedless' leaves neutralized host immunity and enhanced colonization by P. viticola, and the immune-inhibiting activity of PvAvh77 on susceptible Eurasian grapevine depended on its nuclear localization. Using a yeast signal sequence trap approach, we showed that the signal peptide of PvAvh77 is functional in yeast. Moreover, PvAvh77 with a signal peptide stimulated plant immune responses in the apoplast. Notably, application of exogenous purified PvAvh77-M2 effectively initiated defence responses in grapevine extracellularly, as evidenced by increased accumulation of salicylic acid and H2O2, and reduced infection of inoculated P. viticola. In summary, we identified a novel effector, PvAvh77, from P. viticola, which has the potential to serve as an inducer of plant immunity.

Parallel photonic acceleration processor for matrix-matrix multiplication.

We propose and experimentally demonstrate a highly parallel photonic acceleration processor based on a wavelength division multiplexing (WDM) system and a non-coherent Mach-Zehnder interferometer (MZI) array for matrix-matrix multiplication. The dimensional expansion is achieved by WDM devices, which play a crucial role in realizing matrix-matrix multiplication together with the broadband characteristics of an MZI. We implemented a 2 × 2 arbitrary nonnegative valued matrix using a reconfigurable 8 × 8 MZI array structure. Through experimentation, we verified that this structure could achieve 90.5% inference accuracy in a classification task for the Modified National Institute of Standards and Technology (MNIST) handwritten dataset. This provides a new effective solution for large-scale integrated optical computing systems based on convolution acceleration processors.

Multiple-Droplet Selective Manipulation Enabled by Laser-Textured Hydrophobic Magnetism-Responsive Slanted Micropillar Arrays with an Ultrafast Reconfiguration Rate.

Biomimetic structures based on the magnetic response have attracted ever-increasing attention in droplet manipulation. Till now, most methods for droplet manipulation by a magnetic response are only applicable to a single droplet. It is still a challenge to achieve on-demand and precise control of multiple droplets (≥2). In this paper, a strategy for on-demand manipulation of multiple droplets based on magnetism-responsive slanted micropillar arrays (MSMAs) is proposed. The Glaco-modified superhydrophobic surface is the basis of multiple-droplet manipulation. The droplet's motion mode (pinned, unidirectional, and bidirectional) can be readily fine-tuned by changing the volume of droplets and the speed of the magnetic field. The rapid movement of droplets (10-80 mm/s) in the horizontal direction is realized by the unidirectional waves of the micropillar array driven by a specific magnetic field. The bending angle of micropillars can be rapidly and reversibly adjusted from 0 to 90° under the action of a magnetic field. Meanwhile, the liquid-involved light, electric switch, and biomedical detection can be designed by manipulating the droplets on demand. The superiority of MSMAs in multiple-droplet programmable manipulation opens up an avenue for applications in microfluidic and biomedical engineering.

A three-dimensional multiscale model for the prediction of thrombus growth under flow with single-platelet resolution.

Modeling thrombus growth in pathological flows allows evaluation of risk under patient-specific pharmacological, hematological, and hemodynamical conditions. We have developed a 3D multiscale framework for the prediction of thrombus growth under flow on a spatially resolved surface presenting collagen and tissue factor (TF). The multiscale framework is composed of four coupled modules: a Neural Network (NN) that accounts for platelet signaling, a Lattice Kinetic Monte Carlo (LKMC) simulation for tracking platelet positions, a Finite Volume Method (FVM) simulator for solving convection-diffusion-reaction equations describing agonist release and transport, and a Lattice Boltzmann (LB) flow solver for computing the blood flow field over the growing thrombus. A reduced model of the coagulation cascade was embedded into the framework to account for TF-driven thrombin production. The 3D model was first tested against in vitro microfluidics experiments of whole blood perfusion with various antiplatelet agents targeting COX-1, P2Y1, or the IP receptor. The model was able to accurately capture the evolution and morphology of the growing thrombus. Certain problems of 2D models for thrombus growth (artifactual dendritic growth) were naturally avoided with realistic trajectories of platelets in 3D flow. The generalizability of the 3D multiscale solver enabled simulations of important clinical situations, such as cylindrical blood vessels and acute flow narrowing (stenosis). Enhanced platelet-platelet bonding at pathologically high shear rates (e.g., von Willebrand factor unfolding) was required for accurately describing thrombus growth in stenotic flows. Overall, the approach allows consideration of patient-specific platelet signaling and vascular geometry for the prediction of thrombotic episodes.

Nutritive/non-nutritive sweeteners and high fat diet contribute to dysregulation of sweet taste receptors and metabolic derangements in oral, intestinal and central nervous tissues.

OBJECTIVES: Overconsumption of non-nutritive sweeteners is associated with obesity, whereas the underlying mechanisms remain controversial. This study aimed to investigate the effects of long-term consumption of nutritive or non-nutritive sweeteners with or without high fat diet on sweet taste receptor expression in nutrient-sensing tissues and energy regulation dependent on sweet-sensing. METHODS: 50 Male Sprague-Dawley rats (140-160 g) were assigned to 10 groups (n = 5/group). All received fructose at 2.5% or 10%, sucralose at 0.01% or 0.015% or water with a normal chow diet or high fat diet for 12 weeks. Food and drink intake were monitored daily. Oral glucose tolerance test and intraperitoneal glucose tolerance test were performed at week 10 and 11 respectively. Serum was obtained for measurement of biochemical parameters. Tongue, duodenum, jejunum, ileum, colon and hypothalamus were rapidly removed to assess gene expression. RESULTS: Long-term consumption of sweeteners impaired glucose tolerance, increased calorie intake and body weight. A significant upregulation of sweet taste receptor expression was observed in all the four intestinal segments in groups fed 0.01% sucralose or 0.015% sucralose, most strikingly in the ileum, accompanied by elevated serum glucagon-like peptide-1 levels and up-regulated expression of sodium-dependent glucose cotransporter 1 and glucose transporter 2. A significant down-regulation in the tongue and hypothalamus was observed in groups fed 10% fructose or 0.015% sucralose, with alterations in hypothalamic appetite signals. The presence of high fat diet differentially modulates sweet taste perception in nutrient-sensing tissues. CONCLUSIONS: Long-term consumption of whether nutritive sweeteners or non-nutritive sweeteners combined with high fat diet contribute to dysregulation of sweet taste receptor expression in oral, intestinal and central nervous tissues.

GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization.

Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.

The post-discharge coping difficulty of puerperal women in a middle and low-income tourist city during the COVID-19 pandemic.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) pandemic outbreak, the incidence of mental health problems in perinatal women has been high, and particularly prominent in China which was the first country affected by COVID-19. This paper aims to investigate the current situation and the related factors of maternal coping difficulties after discharge during COVID-19. METHODS: General information questionnaires (the Perinatal Maternal Health Literacy Scale, Postpartum Social Support Scale and Post-Discharge Coping Difficulty Scale-New Mother Form) were used to investigate 226 puerperal women in the third week of puerperium. The influencing factors were analyzed by single factor analysis, correlation and multiple linear regression. RESULTS: The total score of coping difficulties after discharge was 48.92 ± 12.05. At the third week after delivery, the scores of health literacy and social support were 21.34 ± 5.18 and 47.96 ± 12.71. There were negative correlations among health literacy, social support and coping difficulties after discharge (r = -0.34, r = -0.38, P < 0.001). Primipara, family income, health literacy and social support were the main factors influencing maternal coping difficulties after discharge. CONCLUSION: During the COVID-19 pandemic, puerperal women in a low- and middle-income city had moderate coping difficulties after discharge and were affected by many factors. To meet the different needs of parturients and improve their psychological coping ability, medical staff should perform adequate assessment of social resources relevant to parturients and their families when they are discharged, so they can smoothly adapt to the role of mothers.

Kurstakin Triggers Multicellular Behaviors in Bacillus cereus AR156 and Enhances Disease Control Efficacy Against Rice Sheath Blight.

Kurstakin is the latest discovered family of lipopeptides secreted by Bacillus spp. In this study, the effects of kurstakin on the direct antagonism, multicellularity, and disease control ability of Bacillus cereus AR156 were explored. An insertion mutation in the nonribosomal peptide synthase responsible for kurstakin synthesis led to a significant reduction of antagonistic ability of AR156 against the plant-pathogenic fungi Rhizoctonia solani, Ascochyta citrullina, Fusarium graminearum, and F. oxysporum f. sp. cubense. The loss of kurstakin synthesis ability significantly impaired the swarming motility of AR156 and reduced biofilm formation and amyloid protein accumulation. Although the loss of kurstakin synthesis ability did not reduce the competitiveness of AR156 under laboratory conditions, the colonization and environmental adaptability of the mutant was significantly weaker than that of wild-type AR156 on rice leaves. The cell surface of wild-type AR156 colonizing the leaf surface was covered by a thick biofilm matrix under a scanning electron microscope, but not the mutant. The colonization ability on rice roots and control efficacy against rice sheath blight disease of the mutant were also impaired. Thus, kurstakin participates in the control of plant diseases by B. cereus AR156 through directly inhibiting the growth of pathogenic fungi and improving long-term environmental adaptability and colonization of AR156 on the host surface by triggering multicellularity. This study explored the multiple functions of kurstakin in plant disease control by B. cereus.

Reconfigurable Magnetic Liquid Metal Robot for High-Performance Droplet Manipulation.

Droplet manipulation is crucial for diverse applications ranging from bioassay to medical diagnosis. Current magnetic-field-driven manipulation strategies are mainly based on fixed or partially tunable structures, which limits their flexibility and versatility. Here, a reconfigurable magnetic liquid metal robot (MLMR) is proposed to address these challenges. Diverse droplet manipulation behaviors including steady transport, oscillatory transport, and release can be achieved by the MLMR, and their underlying physical mechanisms are revealed. Moreover, benefiting from the magnetic-field-induced active deformability and temperature-induced phase transition characteristics, its droplet-loading capacity and shape-locking/unlocking switching can be flexibly adjusted. Because of the fluidity-based adaptive deformability, MLMR can manipulate droplets in challenging confined environments. Significantly, MLMR can accomplish cooperative manipulation of multiple droplets efficiently through on-demand self-splitting and merging. The high-performance droplet manipulation using the reconfigurable and multifunctional MLMR unfolds new potential in microfluidics, biochemistry, and other interdisciplinary fields.

Selenylation Chemistry Suitable for On-Plate Parallel and On-DNA Library Synthesis Enabling High-Throughput Medicinal Chemistry.

Click chemistry is a concept wherein modular synthesis is used for rapid functional discovery. To this end, continuous discovery of clickable chemical transformations is the pillar to support the development of this field. This report details the development of a clickable C3-H selenylation of indole that is suitable for on-plate parallel and DNA-encoded library (SeDEL) synthesis via bioinspired LUMO activation strategy. This reaction is modular, robust and highly site-selective, and it features a simple and mild reaction system (catalyzed by nonmetallic B(C6 F5 )3 at room temperature), high yields and excellent functional group compatibility. Using this method, a library of 1350 indole-selenides was parallel synthesized in an efficient and practical manner, enabling the rapid identification of 3 ai as a promising compound with nanomolar antiproliferative activity in cancer cells via in situ phenotypic screening. These results indicate the great potential of this new clickable selenylation reaction in high-throughput medicinal chemistry and chemical biology.

Liquid biopsy technologies for hematological diseases.

Since the discovery of circulating tumor cells in 1869, technological advances in studying circulating biomarkers from patients' blood have made the diagnosis of nonhematologic cancers less invasive. Technological advances in the detection and analysis of biomarkers provide new opportunities for the characterization of other disease types. When compared with traditional biopsies, liquid biopsy markers, such as exfoliated bladder cancer cells, circulating cell-free DNA (cfDNA), and extracellular vesicles (EV), are considered more convenient than conventional biopsies. Liquid biopsy markers undoubtedly have the potential to influence disease management and treatment dynamics. Our main focuses of this review will be the cell-based, gene-based, and protein-based key liquid biopsy markers (including EV and cfDNA) in disease detection, and discuss the research progress of these biomarkers used in conjunction with liquid biopsy. First, we highlighted the key technologies that have been broadly adopted used in hematological diseases. Second, we introduced the latest technological developments for the specific detection of cardiovascular disease, leukemia, and coronavirus disease. Finally, we concluded with perspectives on these research areas, focusing on the role of microfluidic technology and artificial intelligence in point-of-care medical applications. We believe that the noninvasive capabilities of these technologies have great potential in the development of diagnostics and can influence treatment options, thereby advancing precision disease management.

In Situ Tuning Underwater Bubble Movement on Slippery Lubricant-Infused Anisotropic Microgrooved Surface by Unidirectional Mechanical Strain.

Numerous studies have focused on designing and fabricating functional interfaces that control movement behavior of underwater gas bubbles, which are ubiquitous in a variety of natural and industrial settings. Nevertheless, developing surfaces with in situ tunable bubble movement remain elusive because of current complicated tuning strategies on the specific materials. Inspired by natural pitcher plant and rice leaves, here we report a kind of slippery lubricant-infused anisotropic microgrooved surface (SLI-AMGS) fabricated by femtosecond laser direct writing technology and realize the in situ reversible switching between underwater bubble sliding and pinning by unidirectional mechanical tensile strain. Different experimental parameters including lubricant oil film thickness, bubble volumes and laser power have been researched to manifest the relationship with bubble sliding behaviors. The underlying mechanism of in situ reversible switching mainly lies on the decrease of the lubricant oil film thickness during the process of mechanical stretching in which the uniform and stable oil film layer becomes uneven. This uneven lubricant oil film results in an extraordinary increase of contact angle hysteresis and resistance. At last, we demonstrate a real-time dynamic modulation of the underwater bubble on the SLI-AMGS with a changing mechanical tensile strain for several repeatable times in different acid-based environments. Our work manifests great potential applications in widespread fields including underwater bubble microfluidics and microbubble robots.

Recognition of Bathroom Activities in Older Adults Using Wearable Sensors: A Systematic Review and Recommendations.

This article provides a systematic review of studies on recognising bathroom activities in older adults using wearable sensors. Bathroom activities are an important part of Activities of Daily Living (ADL). The performance on ADL activities is used to predict the ability of older adults to live independently. This paper aims to provide an overview of the studied bathroom activities, the wearable sensors used, different applied methodologies and the tested activity recognition techniques. Six databases were screened up to March 2020, based on four categories of keywords: older adults, activity recognition, bathroom activities and wearable sensors. In total, 4262 unique papers were found, of which only seven met the inclusion criteria. This small number shows that few studies have been conducted in this field. Therefore, in addition, this critical review resulted in several recommendations for future studies. In particular, we recommend to (1) study complex bathroom activities, including multiple movements; (2) recruit participants, especially the target population; (3) conduct both lab and real-life experiments; (4) investigate the optimal number and positions of wearable sensors; (5) choose a suitable annotation method; (6) investigate deep learning models; (7) evaluate the generality of classifiers; and (8) investigate both detection and quality performance of an activity.