Near-Infrared Light-Powered and DNA Nanocage-Confined Catalytic Hairpin Assembly Nanobiosensor with a Nucleic Acid Restriction Behavior and Reinforced Enzymatic Resistance for Robust Imaging Assay in Live Biosystems.

While DNA amplifier-built nanobiosensors featuring a DNA polymerase-free catalytic hairpin assembly (CHA) reaction have shown promise in fluorescence imaging assays within live biosystems, challenges persist due to unsatisfactory precision stemming from premature activation, insufficient sensitivity arising from low reaction kinetics, and poor biostability caused by endonuclease degradation. In this research, we aim to tackle these issues. One aspect involves inserting an analyte-binding unit with a photoinduced cleavage bond to enable a light-powered notion. By utilizing 808 nm near-infrared (NIR) light-excited upconversion luminescence as the ultraviolet source, we achieve entirely a controllable sensing event during the biodelivery phase. Another aspect refers to confining the CHA reaction within the finite space of a DNA self-assembled nanocage. Besides the accelerated kinetics (up to 10-fold enhancement) resulting from the nucleic acid restriction behavior, the DNA nanocage further provides a 3D rigid skeleton to reinforce enzymatic resistance. After selecting a short noncoding microRNA (miRNA-21) as the modeled low-abundance sensing analyte, we have verified that the innovative NIR light-powered and DNA nanocage-confined CHA nanobiosensor possesses remarkably high sensitivity and specificity. More importantly, our sensing system demonstrates a robust imaging capability for this cancer-related universal biomarker in live cells and tumor-bearing mouse bodies, showcasing its potential applications in disease analysis.

Development and validation of an UPLC-MS/MS assay for the simultaneous quantification of seven commonly used antibiotics in human plasma and its application in therapeutic drug monitoring.

OBJECTIVE: To develop and validate an UPLC-MS/MS assay for simultaneous determination of the total concentration of ceftazidime, ciprofloxacin, flucloxacillin, piperacillin, tazobactam, sulfamethoxazole, N-acetyl sulfamethoxazole and trimethoprim, and the protein-unbound concentration of flucloxacillin, in human plasma to be used for research and clinical practice. METHODS: Sample pretreatment included protein precipitation with methanol. For the measurement of protein-unbound flucloxacillin, ultrafiltration was performed at physiological temperature. For all compounds, a stable isotopically labelled internal standard was used. Reliability of the results was assessed by participation in an international quality control programme. RESULTS: The assay was successfully validated according to the EMA guidelines over a concentration range of 0.5-100 mg/L for ceftazidime, 0.05-10 mg/L for ciprofloxacin, 0.4-125 mg/L for flucloxacillin, 0.2-60 mg/L for piperacillin, 0.15-30 mg/L for tazobactam, 1-200 mg/L for sulfamethoxazole and N-acetyl sulfamethoxazole, 0.05-10 mg/L for trimethoprim and 0.10-50 mg/L for unbound flucloxacillin. For measurement of total concentrations, the within- and between-day accuracy ranged from 90.0% to 109%, and 93.4% to 108%, respectively. Within- and between-day precision (variation coefficients, CVs) ranged from 1.70% to 11.2%, and 0.290% to 5.30%, respectively. For unbound flucloxacillin, within-day accuracy ranged from 103% to 106% and between-day accuracy from 102% to 105%. The within- and between-day CVs ranged from 1.92% to 7.11%. Results of the international quality control programme showed that the assay is reliable. CONCLUSIONS: The method provided reliable, precise and accurate measurement of seven commonly prescribed antibiotics, including the unbound concentration of flucloxacillin. This method is now routinely applied in research and clinical practice.

Symbiosis between Dendrobium catenatum protocorms and Serendipita indica involves the plant hypoxia response pathway.

Mycorrhizae are ubiquitous symbioses established between fungi and plant roots. Orchids, in particular, require compatible mycorrhizal fungi for seed germination and protocorm development. Unlike arbuscular mycorrhizal fungi, which have wide host ranges, orchid mycorrhizal fungi are often highly specific to their host orchids. However, the molecular mechanism of orchid mycorrhizal symbiosis is largely unknown compared to that of arbuscular mycorrhizal and rhizobial symbiosis. Here, we report that an endophytic Sebacinales fungus, Serendipita indica, promotes seed germination and the development of protocorms into plantlets in several epiphytic Epidendroideae orchid species (6 species in 2 genera), including Dendrobium catenatum, a critically endangered orchid with high medicinal value. Although plant-pathogen interaction and high meristematic activity can induce the hypoxic response in plants, it has been unclear whether interactions with beneficial fungi, especially mycorrhizal ones, also involve the hypoxic response. By studying the symbiotic relationship between D. catenatum and S. indica, we determined that hypoxia-responsive genes, such as those encoding alcohol dehydrogenase (ADH), are highly induced in symbiotic D. catenatum protocorms. In situ hybridization assay indicated that the ADH gene is predominantly expressed in the basal mycorrhizal region of symbiotic protocorms. Additionally, the ADH inhibitors puerarin and 4-methylpyrazole both decreased S. indica colonization in D. catenatum protocorms. Thus, our study reveals that S. indica is widely compatible with orchids and that ADH and its related hypoxia-responsive pathway are involved in establishing successful symbiotic relationships in germinating orchids.

A population-based study of Helicobacter pylori: Does asymptomatic infection mean no gastroscopic lesions?

OBJECTIVES: We determined the common clinical characteristics of patients infected with Helicobacter pylori (H. pylori) and investigated the relationship between H. pylori infection, and clinical symptoms, and gastroscopic manifestations. Our focus was specifically on the clinical manifestations in asymptomatic patients. METHODS: We obtained the physical examination data of patients who underwent the 14C urea breath test between January 2018 and December 2020 at our Hospital. Basic demographic data, questionnaire data on clinical symptoms, and clinical examination data of the patients were also collected, and the correlation analysis was performed. RESULTS: A total of 2863 participants were included in the study. The overall H. pylori infection rate was 26.30%. The clinical symptoms between H. pylori-positive patients and H. pylori-negative patients did not differ significantly (P > .05). However, H. pylori-positive patients exhibited more severe gastroscopic manifestations (P < .001). The 14C urea breath test disintegrations per minute (DPM) values in H. pylori-positive patients correlated with their serum pepsinogen and gastrin-17 levels. With an increase in the DPM value, more combinations of clinical symptoms appeared in the patients. Among H. pylori-positive patients, DPM levels in asymptomatic patients were lower than those in symptomatic patients (P < .001). However, gastroscopic manifestations did not vary significantly between asymptomatic and symptomatic patients (P > .05). CONCLUSION: Patients infected with H. pylori showed no specific gastrointestinal symptoms. Patients with asymptomatic infection showed lower DPM levels, but their gastroscopic manifestations were similar to those of patients with symptomatic infection, and their lesions were more severe than H. pylori-negative people.

Percutaneous dilatation tracheotomy in patients on extracorporeal membrane oxygenation after cardiac surgery.

BACKGROUND: Current practices regarding percutaneous dilatational tracheostomy in adult patients treated with extracorporeal membrane oxygenation (ECMO) after cardiac surgery is not completely defined. This study aimed to evaluate the safety of the percutaneous dilatational tracheostomy in patients with ECMO after cardiac surgery. METHODS: Between July 2017 and May 2021, 371 ECMO procedures were performed in more than 35,000 adult patients who underwent cardiac surgery in our hospital. Sixty-two patients underwent percutaneous dilatational tracheostomy (PDT) during or after ECMO. A retrospective analysis was performed comparing the incidence of complications and clinical outcomes of the two groups. RESULTS: Of the 371 patients treated with ECMO after adult cardiac surgery during the enrollment period, 22 (7.1%) and 40 (12.8%) underwent PDT during or after ECMO, respectively. The platelet count (PLT) of the day was significantly lower in the PDT during ECMO group (54 (34, 68) vs. 108 (69, 162) (thousands), p < 0.001)). The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the day were longer in the PDT during ECMO group (15.8 (14.6, 19.9) vs. 13.8 (13.2, 15.2) seconds, p = 0.001, 43.8 (38.0, 49.4) vs. 35.2 (28.2, 40.9) seconds, p < 0.001, respectively). There was no significant difference in tracheotomy-related complications between the two groups. Significantly decreased ventilator time was observed in the PDT during ECMO group. CONCLUSIONS: Despite poor coagulation of the day, PDT during ECMO is safe and can appropriately reduce the duration of mechanical ventilation compared with PDT after ECMO weaning in adult patients who have undergone cardiac surgery.

[ST266 inhibits neointimal hyperplasia after arterial balloon injury in rats].

Objective    To examine the effect of Human Amnion-Derived Multipotent Progenitor (AMP) cells and their novel ST266 secretome on neointimal hyperplasia after arterial balloon injury in rats.Material and Methods    Sprague-Dawley male rats were randomly divided into four groups (n=7): Control (PBS) group, systemic ST266 group, systemic AMP group and local AMP implant group. Neointimal hyperplasia was induced in the iliac using a 2F Fogarty embolectomy catheter. After surgery, the rats in the ST266 group were treated with 0.1, 0.5, or 1ml ST266 iv daily. In the systemic AMP groups, a single dose (SD) of 0.5 ×106 or 1×106 AMP cells was injected via the inferior vena cava after arterial balloon injury. In local AMP implant groups, 1×106, 5×106, or 20×106 AMP cells were implanted in 300 µl Matrigel (Mtgl) around the iliac artery after balloon injury. The iliac arteries were removed for histologic analysis at 28 days after the surgery. Re-endothelialization index was measured at 10 days after balloon injury.Results    ST266 (1 ml) group had a lower level of the Neointima / Neointima+Media ratio (N / N+M) 0.3±0.1 vs 0.5±0.1, p=0.004) and luminal stenosis (LS) percentage (18.2±1.9 % vs 39.2±5.8 %, p=0.008) compared with the control group. Single-dose AMP (1×106) decreased LS compared to the control group (19.5±5.4 % vs 39.2±5.8 %, p=0.033). Significant reduction in N / N+M were found between implanted AMPs (20×106) and the control group (0.4±0.1 vs 0.5±0.1, p=0.003) and the Mtgl-only group (0.5±0.1, p=0.007). Implanted AMPs (20×106) decreased the LS compared with both the control (39.2±5.8 %, p=0.001) and Mtgl-only group (37.5±8.6 %, p=0.016). ST266 (1 ml) significantly increased the re-endothelialization index compared to the control (0.4±0.1 vs 0.1±0.1, p=0.002).Conclusion    ST266 and AMP cells reduce neointimal formation and increase the re-endothelialization index after arterial balloon injury. ST266 is potentially a novel, therapeutic agent to prevent vascular restenosis in human.

A Self-Made Optical Tweezers Integrated Upconversion Luminescence Confocal Scanning Instrument Enables Stable and Noninvasive Long-Term In Situ Imaging a Single Suspension Cell Under Exceptionally Efficient Luminescent Resonance Energy Transfer Sensing.

It is necessary to explore labeling probes with worthy optical properties and a noninvasive fluorescence imaging manner for stable long-term in situ measuring a single suspension cell. In response to these goals, we herein make a breakthrough on two fronts. On one hand, a co-sensitizer-induced efficient 808 nm near-infrared light-excited luminescence-confined upconversion nanoparticle with a low thermal effect is fabricated by employing a layer-by-layer seed growing approach to develop a sandwich structure, under which the luminescence domain is vastly restricted into an extremely thin inner shell (∼ 2.77 nm) to finally bring about a high-efficiency luminescent resonance energy transfer (LRET) sensing behavior. On the other hand, a self-made optical tweezers integrated upconversion luminescence confocal scanning instrument is applied to enhance the imaging accuracy, after which the liquid viscous force is sufficiently overcome by the resulting single beam gradient force and the analyzed suspension cell is always immobilized to the focal plane to ensure a constant luminescence excitation condition. By making use of a metal ion-dependent DNAzyme and a hairpin DNA strand to design a corresponding LRET sensing system, our nanoprobe shows satisfactory assay performance for two model biomolecules (Ca2+ and TK1 messenger RNA). Following the optical trapping-assisted imaging, this exceptional measurement method is capable of effectively monitoring the intracellular target changes in different physiological states, endowing a powerful toolbox for single cell analysis.

Upconversion Luminescence-Initiated and GSH-Responsive Self-Driven DNA Motor for Automatic Operation in Living Cells and In Vivo.

In light of the worthy design flexibility and the good signal amplification capacity, the recently developed DNA motor (especially the DNA walker)-based fluorescent biosensors can offer an admirable choice for realizing bioimaging. However, this attractive biosensing strategy not only has the disadvantage of uncontrollable initiation but also usually demands the supplement of exogenous driving forces. To handle the above obstacles, some rewarding solutions are proposed here. First, on the surface of an 808 nm near-infrared light-excited low-heat upconversion nanoparticle, a special ultraviolet upconversion luminescence-initiated three-dimensional (3D) walking behavior is performed by embedding a photocleavage linker into the sensing elements, and such light-controlled target recognition can perfectly overcome the pre-triggering of the biosensor during the biological delivery to significantly boost the sensing precision. After that, a peculiar self-driven walking pattern is constructed by employing MnO2 nanosheets as an additional nanovector to physically absorb the sensing frame, for which the reduction of the widespread glutathione in the biological medium can bring about sufficient self-supplied Mn2+ to guarantee the walking efficiency. By selecting an underlying next-generation broad-spectrum cancer biomarker (survivin messenger RNA) as the model target, we obtain that the newly formed autonomous 3D DNA motor shows a commendable sensitivity (where the limit of detection is down to 0.51 pM) and even an outstanding specificity for distinguishing single-base mismatching. Beyond this sound assay performance, our sensing approach is capable of working as a powerful imaging platform for accurately operating in various living specimens such as cells and bodies, showing a favorable diagnostic ability for cancer care.

Inhibiting microRNA-155 attenuates atrial fibrillation by targeting CACNA1C.

BACKGROUND: Reduction in L-type Ca2+ current (ICa,L) density is a hallmark of the electrical remodeling in atrial fibrillation (AF). The expression of miR-155, whose predicted target gene is the α1c subunit of the calcium channel (CACNA1C), was upregulated in atrial cardiomyocytes (aCMs) from patients with paroxysmal AF.The study is to determine miR-155 could target the gene expression of ICa,L and contribute to electrical remodeling in AF. METHODS: The expression of miR-155 and CACNA1C was assessed in aCMs from patients with paroxysmal AF and healthy control. ICa,L properties were observed after miR-155 transfection in human induced pluripotent stem cell derived atrial cardiomyocytes (hiPSC-aCMs). Furthermore, an miR-155 transgene (Tg) and knock-out (KO) mouse model was generated to determine whether miR-155 was involved in ICa,L-related electrical remodeling in AF by targeting CACNA1C. RESULTS: The expression level of miR-155 was increased, while the expression level of CACNA1C reduced in the aCMs of patients with AF. miR-155 transfection in hiPSC-aCMs produced changes in ICa,L properties qualitatively similar to those produced by AF. miR-155/Tg mice developed a shortened action potential duration and increased vulnerability to AF, which was associated with decreased ICa,L and attenuated by an miR-155 inhibitor. Finally, the genetic inhibition of miR-155 prevented AF induction in miR-155/KO mice with no changes in ICa,L properties. CONCLUSIONS: The increased miR-155 expression in aCMs was sufficient for the reduction in the density of ICa,L and the underlying electronic remodeling. The inhibition of miR-155 prevented ICa,L-related electric remodeling in AF and might constitute a novel anti-AF approach targeting electrical remodeling.

MicroRNA-146b-5p promotes atrial fibrosis in atrial fibrillation by repressing TIMP4.

Alteration of tissue inhibitors of matrix metalloproteinases (TIMP)/matrix metalloproteinases (MMP) associated with collagen upregulation has an important role in sustained atrial fibrillation (AF). The expression of miR-146b-5p, whose the targeted gene is TIMPs, is upregulated in atrial cardiomyocytes during AF. This study was to determine whether miR-146b-5p could regulate the gene expression of TIMP4 and the contribution of miRNA to atrial fibrosis in AF. Collagen synthesis was observed after miR-146b-5p transfection in human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs)-fibroblast co-culture cellular model in vitro. Furthermore, a myocardial infarction (MI) mouse model was used to confirm the protective effect of miR-146b-5p downregulation on atrial fibrosis. The expression level of miR-146b-5p was upregulated, while the expression level of TIMP4 was downregulated in the fibrotic atrium of canine with AF. miR-146b-5p transfection in hiPSC-aCMs-fibroblast co-culture cellular model increased collagen synthesis by regulating TIMP4/MMP9 mediated extracellular matrix proteins synthesis. The inhibition of miR-146b-5p expression reduced the phenotypes of cardiac fibrosis in the MI mouse model. Fibrotic marker MMP9, TGFB1 and COL1A1 were significantly downregulated, while TIMP4 was significantly upregulated (at both mRNA and protein levels) by miR-146b-5p inhibition in cardiomyocytes of MI heart. We concluded that collagen fibres were accumulated in extracellular space on miR-146b-5p overexpressed co-culture cellular model. Moreover, the cardiac fibrosis induced by MI was attenuated in antagomiR-146 treated mice by increasing the expression of TIMP4, which indicated that the inhibition of miR-146b-5p might become an effective therapeutic approach for preventing atrial fibrosis.

A mutant-cell library for systematic analysis of heparan sulfate structure-function relationships.

Heparan sulfate (HS) is a complex linear polysaccharide that modulates a wide range of biological functions. Elucidating the structure-function relationship of HS has been challenging. Here we report the generation of an HS-mutant mouse lung endothelial cell library by systematic deletion of HS genes expressed in the cell. We used this library to (1) determine that the strictly defined fine structure of HS, not its overall degree of sulfation, is more important for FGF2-FGFR1 signaling; (2) define the epitope features of commonly used anti-HS phage display antibodies; and (3) delineate the fine inter-regulation networks by which HS genes modify HS and chain length in mammalian cells at a cell-type-specific level. Our mutant-cell library will allow robust and systematic interrogation of the roles and related structures of HS in a cellular context.

Strengthened rebamipide ocular nanoformulation to effectively treat corneal alkali burns in mice through the HMGB1 signaling pathway.

Corneal alkali burns are a major ophthalmic emergency, as current therapeutic treatments are limited. Novel treatment targets and new potential agents are required to combat this severe ocular injury. Glycyrrhizin and rebamipide (RBM) are both FDA-approved drugs with potential effects against corneal alkali burns, but RBM is limited by its low aqueous solubility and low bioavailability. This study aimed to utilize dipotassium glycyrrhizinate (DG, a dipotassium salt of glycyrrhizin) as a nanocarrier encapsulating RBM to formulate an ophthalmic solution (marked DG-RBM) with strengthened activities to treat corneal alkali burns. Results showed that an easy DG-RBM preparative process generated particles with high encapsulation efficacy and ultra-small micellar size. The solubility of RBM in DG-RBM in aqueous solution was 3.1 × 105-fold enhanced than its free solution. DG-RBM exhibited excellent storage stability. In vitro cytotoxicity, ex vivo conjunctival responses, and rabbit eye tolerance tests showed that DG-RBM possessed good ocular safety profiles. DG-RBM exhibited improved in vivo corneal permeation profiles and demonstrated a strong effect against H2O2-induced oxidative damage, with a significant effect on promoting epithelial wound healing in corneal cells in vitro. As expected, in a mouse model of corneal alkali burns, the topical administration of DG-RBM achieved a strengthened efficacy against alkali burn damages. The mechanism of this therapeutic effect involved regulating high-mobility group box 1 (HMGB1) signaling and its related angiogenic and proinflammatory cytokines. These findings demonstrate the ease of preparing DG-RBM and its great potential as a novel ocular topical formulation to treat corneal alkali burns by regulating HMGB1 signaling.

Glycyrrhizin micelle as a genistein nanocarrier: Synergistically promoting corneal epithelial wound healing through blockage of the HMGB1 signaling pathway in diabetic mice.

The purpose of this study was to explore the feasibility of targeting the HMGB1 signaling pathway to treat diabetic keratopathy with a dipotassium glycyrrhizinate-based micelle ophthalmic solution encapsulating genistein (DG-Gen), and to evaluate whether these dipotassium glycyrrhizinate (DG) micelles could synergistically enhance the therapeutic effect of encapsulated genistein (Gen). An optimized DG-Gen ophthalmic solution was fabricated with a Gen/DG weight of ratio 1:15, and this formulation featured an encapsulation efficiency of 98.96 ± 0.82%, and an average particle size of 29.50 ± 2.05 nm. The DG-Gen ophthalmic solution was observed to have good in vivo ocular tolerance and excellent in vivo corneal permeation, and to remarkably improve in vitro antioxidant activity. Ocular topical application of the DG-Gen ophthalmic solution significantly prompted corneal re-epithelialization and nerve regeneration in diabetic mice, and this efficacy might be due to the inhibition of HMGB1 signaling through down-regulation of HMGB1 and its receptors RAGE and TLR4, as well as inflammatory factor interleukin (IL)-6 and IL-1ß. In conclusion, these data showed that HMGB1 signaling is a potential regulation target for the treatment of diabetic keratopathy, and novel DG-micelle formulation encapsulating active agents such as Gen could synergistically cause blockage of HMGB1 signaling to prompt diabetic corneal and nerve wound healing.

Effect of fermentation bed on bacterial growth in the fermentation mattress material and cecum of ducks.

The composition of microorganisms in the gastrointestinal tract is closely related to the intestinal microenvironments and the exterior growth environments of host. In this study, 16S rDNA sequencing technology was adopted to investigate the influence of fermentation bed on the cecum microorganisms of ducks. Two feeding density treatment groups were set up, including group A (n = 4brids/m2) and group B (n = 6brids/m2). Samples were collected from the intermediate core fermentation layer (10-20 cm) of the fermented mattress materials and from the intestinal contents of ducks at 4, 6 and 8 weeks, respectively. Results showed that Bacteroidetes (20.12-27.17%) and Ruminococcaceae UCG-014 (2.97-10.1%) were the predominant microorganisms in duck cecum, while the Truepera (5.08-6.29%), Pricia (4.44-5.44%) and Luteimonas (3.62-4.99%) were the dominant microorganisms in fermentation mattress material. The cecum bacteria exhibited great difference among different growth periods of the ducks. Increasing the stocking density of ducks had a negative effect on the beneficial bacteria in the cecum. The microbial populations in fermentation mattress material were very different from that in the cecal. In summary, our findings can provide a scientific data for the rational use of fermentation bed feeding mode in poultry production.

Stretching Hookean ribbons part II: from buckling instability to far-from-threshold wrinkle pattern.

We address the fully developed wrinkle pattern formed upon stretching a Hookean, rectangular-shaped sheet, when the longitudinal tensile load induces transverse compression that far exceeds the stability threshold of a purely planar deformation. At this "far-from-threshold" parameter regime, which has been the subject of the celebrated Cerda-Mahadevan model (Cerda and Mahadevan in Phys Rev Lett 90:074302, 2003), the wrinkle pattern expands throughout the length of the sheet and the characteristic wavelength of undulations is much smaller than its width. Employing Surface Evolver simulations over a range of sheet thicknesses and tensile loads, we elucidate the theoretical underpinnings of the far-from-threshold framework in this setup. We show that the evolution of wrinkles comes in tandem with collapse of transverse compressive stress, rather than vanishing transverse strain (which was hypothesized by Cerda and Mahadevan in Phys Rev Lett 90:074302, 2003), such that the stress field approaches asymptotically a compression-free limit, describable by tension field theory. We compute the compression-free stress field by simulating a Hookean sheet that has finite stretching modulus but no bending rigidity, and show that this singular limit encapsulates the geometrical nonlinearity underlying the amplitude-wavelength ratio of wrinkle patterns in physical, highly bendable sheets, even though the actual strains may be so small that the local mechanics is perfectly Hookean. Finally, we revisit the balance of bending and stretching energies that gives rise to a favorable wrinkle wavelength, and study the consequent dependence of the wavelength on the tensile load as well as the thickness and length of the sheet.

Stretching Hookean ribbons part I: relative edge extension underlies transverse compression and buckling instability.

The wrinkle pattern exhibited upon stretching a rectangular sheet has attracted considerable interest in the "extreme mechanics" community. Nevertheless, key aspects of this notable phenomenon remain elusive. Specifically-what is the origin of the compressive stress underlying the instability of the planar state? what is the nature of the ensuing bifurcation? how does the shape evolve from a critical, near-threshold regime to a fully developed pattern of parallel wrinkles that permeate most of the sheet? In this paper we address some of these questions through numerical simulations and analytic study of the planar state in Hookean sheets. We show that transverse compression is a boundary effect, which originates from the relative extension of the clamped edges with respect to the transversely contracted, compression-free bulk of the sheet, and draw analogy between this edge-induced compression and Moffatt vortices in viscous, cavity-driven flow. Next, we address the instability of the planar state and show that it gives rise to a buckling pattern, localized near the clamped edges, which evolves-upon increasing the tensile load-to wrinkles that invade the uncompressed portion of the sheet. Crucially, we show that the key aspects of the process-from the formation of transversely compressed zones, to the consequent instability of the planar state and the emergence of a wrinkle pattern-can be understood within a Hookean framework, where the only origin of nonlinear response is geometric, rather than a non-Hookean stress-strain relation.

Exposure-time-dependent subcellular staging of gold nanoparticles deposition and vesicle destruction in mice livers.

Several advances in nanomedicine have been accompanied by rising concerns about the bioaccumulation and toxicity of gold nanoparticles (AuNPs). Here, we assessed the in vivo fate of diversely sized AuNPs that were injected into mice as a computed tomography contrast agent and examined with multi-scale analyses across the organ, tissue, cell, and subcellular levels. After focusing on the strong detected accumulation in livers, our data revealed a set of three clear, exposure-time-dependent patterns based on i) AuNPs deposit morphology and ii) readily identifiable phenotypes for AuNP-impacted subcellular vesicles. Importantly, we detected no obvious differences in liver function, liver cell apoptosis, or autophagy upon exposure to AuNPs. Thus, our study illustrates an accessible experimental and high-resolution data interpretation framework for quickly obtaining and contextualizing informative trends about any AuNP-triggered patterns of subcellular damage in nanomedicine studies; these can help guide cytotoxity and safety testing of diagnostic nanomedical technologies.

Enhancing CO2 utilization by a physical absorption-based technique in microalgae culture.

Carbon dioxide supplementation is significant for cell growth in autotrophic cultures of microalgae. However, the CO2 utilization efficiency is quite low in most processes. Aimed at this problem, six kinds of physical absorption enhancers were investigated to enhance the biological carbon sequestration of microalgae. By the addition of a small amount of CO2 absorption enhancer, the total inorganic carbon concentration of the medium was significantly increased. In addition, the biomass productivity of Scenedesmus dimorphus was maximally increased by 63% by the addition of propylene carbonate in flask cultures. In cultures using an air-lift photobioreactor equipped with a pH-feedback control system to supply CO2, the CO2 consumption was maximally reduced by 71% with added polyethylene glycol dimethyl ether. This study indicates that the incorporation of physical absorption enhancers could be a promising approach to overcome the problems of low CO2 utilization efficiency and high carbon source cost in algal biomass production.

[Application and Progress of Convolutional Neural Network-based Pathological Diagnosis of Gastric Cancer].

The incidence of gastric cancer is the highest among all kinds of malignant tumors in China. Because gastric cancer is very hard to identify in its early stage, the early diagnosis rate of gastric cancer in China is relatively low. At present, the pathological diagnosis of gastric cancer mainly depends on the diagnosis of pathologists. However, the gradual improvement of people's living standards and the growing demand for medical and health care have exacerbated the shortage of medical resources, which has become a even more serious problem. Therefore, there is an urgent need for new technologies to help deal with this challenge. In recent years, with the rapid development of artificial intelligence (AI) and digital pathology, AI-aided pathological diagnosis based on convolutional neural network (CNN) as the core technology is showing promises for improving the diagnostic efficiency of gastric cancer. It is also of great significance for the early diagnosis and treatment of the disease and the reduction of its high incidence and mortality. We herein summarize the application and progress of deep-learning CNN in pathological diagnosis of gastric cancer, as well as the existing problems and prospects of future development.

[An integrative metabolomics and network pharmacology method for exploring bioactive components and preliminary pharmacodynamics in medicinal parts of Harrisonia perforata].

In this paper,metabolomics and network pharmacology were used to investigate the bioactive components of Harrisonia perforata and their possible mechanisms of action. Metabolites in the flowers,fruits,branches,leaves and stalks of H. perforata were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Meanwhile,multiple statistical analysis methods including principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA)were applied to screen and identify differential compounds. With metabolomics method,9 differential compounds were preliminarily identified from leaves and other non-traditional medicinal parts. Subsequently,these compounds were explored by using network pharmacology. With gastrointestinal absorption and drug-likeness as limiting conditions,they were imported into the Swiss ADME,from which 7 compounds with potential medicinal activity were obtained. Then,their targets were predicted by PharmMapper,with Human Protein Targets Only and Normalized Fit Score>0. 9 set as limiting conditions,and 60 standardized potential targets were identified with Uniprot. KEGG( Kyoto encyclopedia of genes and genomes) pathway data was obtained using metascape and the " potential active ingredients-target-pathway" network was constructed with Cytoscape 3. 7. 2. The enrichment analysis of KEGG demonstrated that the 60 targets were enriched in 78 signaling pathways( min overlap: 3,P value cutoff: 0. 01,min enrichment: 1. 5),many of which are related to anti-bacteria,anti-inflammation and anti-virus,such as IL-17 signaling pathway,RIG-I-like receptor signaling pathway and NOD-like receptor signaling pathway. Finally,depending on the clinical activity of H. perforata,the relevant signaling pathways were analyzed through experimental data and literature. Dehydroconiferyl alcohol was reported to have the anti-inflammatory effect and perforamone D to possess the antimycobacterial activity. The KEGG pathway enrichment analysis showed that dehydroconiferyl alcohol could act on the Alzheimer's disease( AD) signaling pathway by targeting CDK5 R1 and BACE1. ACh E inhibitor is the most promising drug to treat AD,while dehydroconiferyl alcohol has been proved to inhibit ACh E according to literature. The experimental results revealed that the extract of leaves of H. perforata can effectively inhibit the growth of Staphylococcus aureus. These are consistent with the enrichment analysis results of KEGG. This study explored the bioactive components and pharmacodynamics of the leaves of the H. perforata,laying a theoretical foundation for its in-depth development and rational application.