Evaluation of tumor microvasculature with 3D ultrasound localization microscopy based on 2D matrix array.

OBJECTIVE: Evaluation of tumor microvascular morphology is of great significance in tumor diagnosis, therapeutic effect prediction, and surgical planning. Recently, two-dimensional ultrasound localization microscopy (2DULM) has demonstrated its superiority in the field of microvascular imaging. However, it suffers from planar dependence and is unintuitive. We propose a novel three-dimensional ultrasound localization microscopy (3DULM) to avoid these limitations. METHODS: We investigated 3DULM based on a 2D array for tumor microvascular imaging. After intravenous injection of contrast agents, all elements of the 2D array transmit and receive signals to ensure a high and stable frame rate. Microbubble signal extraction, filtering, positioning, tracking, and other processing were used to obtain a 3D vascular map, flow velocity, and flow direction. To verify the effectiveness of 3DULM, it was validated on double helix tubes and rabbit VX2 tumors. Cisplatin was used to verify the ability of 3DULM to detect microvascular changes during tumor treatment. RESULTS: In vitro, the sizes measured by 3DULM at 3 mm and 13 mm were 178 µ m and 182 µ m , respectively. In the rabbit tumors, we acquired 9000 volumes to reveal vessels about 30 µ m in diameter, which surpasses the diffraction limit of ultrasound in traditional ultrasound imaging, and the results matched with micro-angiography. In addition, there were significant changes in vascular density and curvature between the treatment and control groups. CONCLUSIONS: The effectiveness of 3DULM was verified in vitro and in vivo. Hence, 3DULM may have potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease. CLINICAL RELEVANCE STATEMENT: 3D ultrasound localization microscopy is highly sensitive to microvascular changes; thus, it has clinical potential for tumor diagnosis and treatment evaluation. KEY POINTS: • 3D ultrasound localization microscopy is demonstrated on double helix tubes and rabbit VX2 tumors. • 3D ultrasound localization microscopy can reveal vessels about 30 µ m in diameter-far smaller than traditional ultrasound. • This form of imaging has potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease.

New mechanistic understanding of osteoclast differentiation and bone resorption mediated by P2X7 receptors and PI3K-Akt-GSK3ß signaling.

OBJECTIVE: Osteoporosis is a global health issue characterized by decreased bone mass and microstructural degradation, leading to an increased risk of fractures. This study aims to explore the molecular mechanism by which P2X7 receptors influence osteoclast formation and bone resorption through the PI3K-Akt-GSK3ß signaling pathway. METHODS: An osteoporosis mouse model was generated through ovariectomy (OVX) in normal C57BL/6 and P2X7f/f; LysM-cre mice. Osteoclasts were isolated for transcriptomic analysis, and differentially expressed genes were selected for functional enrichment analysis. Metabolite analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and multivariate statistical analysis and pattern recognition were used to identify differential lipid metabolism markers and their distribution. Bioinformatics analyses were conducted using the Encyclopedia of Genes and Genomes database and the MetaboAnalyst database to assess potential biomarkers and create a metabolic pathway map. Osteoclast precursor cells were used for in vitro cell experiments, evaluating cell viability and proliferation using the Cell Counting Kit 8 (CCK-8) assay. Osteoclast precursor cells were induced to differentiate into osteoclasts using macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-beta ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) staining was performed to compare differentiation morphology, size, and quantity between different groups. Western blot analysis was used to assess the expression of differentiation markers, fusion gene markers, and bone resorption ability markers in osteoclasts. Immunofluorescence staining was employed to examine the spatial distribution and quantity of osteoclast cell skeletons, P2X7 protein, and cell nuclei, while pit assay was used to evaluate osteoclast bone resorption ability. Finally, in vivo animal experiments, including micro computed tomography (micro-CT), hematoxylin and eosin (HE) staining, TRAP staining, and immunohistochemistry, were conducted to observe bone tissue morphology, osteoclast differentiation, and the phosphorylation level of the PI3K-Akt-GSK3ß signaling pathway. RESULTS: Transcriptomic and metabolomic data collectively reveal that the P2X7 receptor can impact the pathogenesis of osteoporosis through the PI3K-Akt-GSK3ß signaling pathway. Subsequent in vitro experiments showed that cells in the Sh-P2X7 + Recilisib group exhibited increased proliferative activity (1.15 versus 0.59), higher absorbance levels (0.68 versus 0.34), and a significant increase in resorption pit area (13.94 versus 3.50). Expression levels of osteoclast differentiation-related proteins MMP-9, CK, and NFATc1 were markedly elevated (MMP-9: 1.72 versus 0.96; CK: 2.54 versus 0.95; NFATc1: 3.05 versus 0.95), along with increased fluorescent intensity of F-actin rings. In contrast, the OE-P2X7 + LY294002 group showed decreased proliferative activity (0.64 versus 1.29), reduced absorbance (0.34 versus 0.82), and a significant decrease in resorption pit area (5.01 versus 14.96), accompanied by weakened expression of MMP-9, CK, and NFATc1 (MMP-9: 1.14 versus 1.79; CK: 1.26 versus 2.75; NFATc1: 1.17 versus 2.90) and decreased F-actin fluorescent intensity. Furthermore, in vivo animal experiments demonstrated that compared with the wild type (WT) + Sham group, mice in the WT + OVX group exhibited significantly increased levels of CTX and NTX in serum (CTX: 587.17 versus 129.33; NTX: 386.00 versus 98.83), a notable decrease in calcium deposition (19.67 versus 53.83), significant reduction in bone density, increased trabecular separation, and lowered bone mineral density (BMD). When compared with the KO + OVX group, mice in the KO + OVX + recilisib group showed a substantial increase in CTX and NTX levels in serum (CTX: 503.50 versus 209.83; NTX: 339.83 versus 127.00), further reduction in calcium deposition (29.67 versus 45.33), as well as decreased bone density, increased trabecular separation, and reduced BMD. CONCLUSION: P2X7 receptors positively regulate osteoclast formation and bone resorption by activating the PI3K-Akt-GSK3ß signaling pathway.

Locking plate combined with titanium cable for Neer type II distal clavicle fractures.

BACKGROUND: There is controversy about the optimal strategy treatment of unstable distal clavicle fractures. We explored use of a surgical strategy: combination of a distal clavicle locking plate and a titanium cable. The purpose of this retrospective case series study was to evaluate the clinical outcomes of this new strategy in treating Neer type II distal clavicle fractures. METHODS: Twenty-one patients with Neer type II distal clavicle fracture were treated with a distal clavicle locking plate and a titanium cable. All patients were followed for at least one year. We retrospectively collected and reviewed follow-up data. The clinical outcomes were assessed for union rate, functional score, and complication rate. RESULTS: All patients achieved bony union within 6 months. The average follow-up period was 20.6 months (range12-48 months). The mean Constant score at one-year follow-up was 94.6 ± 3.3 (range 84-98), and the mean UCLA (University of California, Los Angeles) score was 33.3 ± 2.6 (range 27-35). Only one complication (wound infection) was observed during follow-up. Two patients received another operation for implant removal due to local irritation. CONCLUSIONS: Use of a distal clavicle locking plate in combination with a titanium cable for treatment of Neer type II fractures results in high union rate, a low complication rate, and good shoulder function. This combined surgical strategy can be considered an effective method for treating unstable distal clavicle fractures.

Three-dimensional spiral motion of microparticles by a binary-phase logarithmic-spiral zone plate.

Acoustic vortex beams, which have both linear and angular momentum, can be used to make precise acoustic tweezers. Limited by the symmetry of a normal vortex beam, these tweezers are usually used for trapping or rotating particles in two dimensions. Here, the three-dimensional spiral motion of two soft particles of different sizes was realized using a vortex beam with a twisted focus, which was synthesized by a silicone binary-phase logarithmic-spiral zone plate. Numerical simulations and experimental measurements demonstrated that the beam had anisotropic focuses of crescent transverse intensity profiles and a screw phase dislocation with a singularity at the center. Experiments showed that a small particle (k0r ≈ 1.3) can follow the twisted intensity of the beam, but a large particle (k0r ≈ 4.7) spirals up away from the twisted field pattern. This is attributed to the dominant gradient force for the small particle, whereas the scattering effect induced a scattering force combined with a gradient force for the large particle. This focused twisted beam, which was generated with a structured silicone plate, and the three-dimensional spiral motion of microparticles, advance the development of simple, compact, and disposable acoustic devices for the precise and diverse manipulation of microparticles.

Traditional Uses, Origins, Chemistry and Pharmacology of Bombyx batryticatus: A Review.

Bombyx batryticatus (B. batryticatus), a well-known traditional animal Chinese medicine, has been commonly used in China for thousands of years. The present paper reviewed advances in traditional uses, origin, chemical constituents, pharmacology and toxicity studies of B. batryticatus. The aim of the paper is to provide more comprehensive references for modern B. batryticatus study and application. In Traditional Chinese Medicine (TCM) culture, drugs containing B. batryticatus have been used to treat convulsions, headaches, skin prurigo, scrofula, tonsillitis and fever. Many studies indicate B. batryticatus contains various compounds, including protein and peptides, fatty acids, flavonoids, nucleosides, steroids, coumarin, polysaccharide and others. Numerous investigations also have shown that extracts and compounds from B. batryticatus exert a wide spectrum of pharmacological effects both in vivo and in vitro, including effects on the nervous system, anticoagulant effects, antitumor effects, antibacterial and antifungal effects, antioxidant effects, hypoglycemic effects, as well as other effects. However, further studies should be undertaken to investigate bioactive compounds (especially proteins and peptides), toxic constituents, using forms and the quality evaluation and control of B. batryticatus. Furthermore, it will be interesting to study the mechanism of biological activities and structure-function relationships of bioactive constituents in B. batryticatus.

Treatment of distal tibial shaft fractures by three different surgical methods: a randomized, prospective study.

PURPOSE: A few studies focused on the methods of treatment for displaced distal tibial shaft fractures have been published, all of which compared two different methods. In this randomized, prospective study, we aimed to compare minimally invasive plate osteosynthesis, locking intramedullary nail stabilization and external fixation combined with limited open reduction and absorbable internal fixation for distal tibial shaft fractures by assessing complications and secondary procedures. METHODS: From November 2002 to June 2012, 137 skeletally mature patients with displaced distal tibial shaft fractures with or without fibula fracture were randomized to be treated by minimally invasive plate osteosynthesis (group A, n = 46), locking intramedullary nail (group B, n = 46) or external fixation combined with limited open reduction and absorbable internal fixation (group C, n = 45). Age, gender, mechanism of injury, fracture pattern and presence of open fracture were equally distributed among the three groups. Indexes for evaluation included hospital stay, operative time, time to radiographic union, union status, infection and the incidence of re-operation. Mazur ankle score was introduced for functional evaluation. Statistics Analysis System (SAS) 9.2 was used for analysis. RESULTS: A total of 121 patients were included in the final analysis (group A 42, group B 40 and group C 39) and evaluated after a mean of 14.8 months follow-up. There was no significant difference (P > 0.05) in hospital stay, time to radiographic union and the incidence of union status among the three groups. Although group C was associated with less secondary procedures versus groups A and B, it was related with more pin tract infections (15.4 %). Anterior knee pain occurred frequently after locking intramedullary nailing (37.5 %) and the irritation symptoms were more frequently encountered in group A (59.5 %). There was no difference in ankle function between the three methods after operation (P > 0.05). CONCLUSIONS: We consider that the minimally invasive plate osteosynthesis, locking intramedullary nail stabilization and external fixation combined with limited open reduction and absorbable internal fixation techniques are all efficient methods for treating distal tibia fractures. With its wide indications, external fixation combined with limited open reduction and absorbable internal fixation leads to minimal soft tissue complication, good functional result and no local soft tissue irritation or implant removal.

Covalent organic framework based cytoprotective therapy after ischemic stroke.

Cytoprotection has emerged as an effective therapeutic strategy for mitigating brain injury following acute ischemic stroke (AIS). The sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) channel plays a pivotal role in brain edema and neuroinflammation. However, the practical use of the inhibitor glyburide (GLB) is hindered by its low bioavailability. Additionally, the elevated reactive oxygen species (ROS) after AIS exacerbate SUR1-TRPM4 activation, contributing to irreversible brain damage. To overcome these challenges, GLB and superoxide dismutase (SOD) were embedded in a covalent organic framework (COF) with a porous structure and great stability. The resulting S/G@COF demonstrated significant improvements in survival and neurological functions. This was achieved by eliminating ROS, preventing neuronal loss and apoptosis, suppressing neuroinflammation, modulating microglia activation, and ameliorating blood-brain barrier (BBB) disruption. Mechanistic investigations revealed that S/G@COF concurrently activated the Wnt/ß-catenin signaling pathway while suppressing the upregulation of SUR1-TRPM4. This study underscores the potential of employing multi-target therapy and drug modification in cytoprotective strategies for ischemic stroke.

Skin-Conformable Flexible and Stretchable Ultrasound Transducer for Wearable Imaging.

Ultrasound imaging offers a noninvasive, radiation-free method for visualizing internal tissues and organs, with deep penetration capabilities. This has established it as a crucial tool for physicians in diagnosing internal tissue pathologies and monitoring human conditions. Nonetheless, conventional ultrasound probes are often characterized by their rigidity and bulkiness. Designing a transducer that can seamlessly adapt to the contours and dynamics of soft, curved human skin presents significant technical hurdles. We present a novel flexible and stretchable ultrasound transducer (FSUT) designed for adaptability to large-curvature surfaces while preserving superior imaging quality. Central to this breakthrough is the innovative use of screen-printed silver nanowires (AgNWs) coupled with a composite elastic substrate, together ensuring robust and stable electrical and mechanical connections. Standard tensile and fatigue tests verify its durability. The mechanical, electrical, and acoustic properties of FSUTs are characterized using standard methods, with large tensile strains (≥110%), high flexibility ( R ≥ 1.4 mm), and lightweight ( ≤ 1.58 g) to meet the needs of wearable devices. Center frequency and -6-dB bandwidth are approximately 5.3 MHz and 66.47%, respectively. Images of the commercial anechoic cyst phantom yielded an axial and lateral resolution (depths of 10-70 mm) of approximately 0.31 and 0.46, and 0.34 and 0.84 mm, respectively. The complex curved surface imaging capabilities of FSUT were tested on agar-gelatin-based breast cyst phantoms under different curvatures. Finally, ultrasound images of the thyroid, brachial, and carotid arteries were also obtained from volunteer wearing FSUT.

Treatment of type C pilon fractures by external fixator combined with limited open reduction and absorbable internal fixation.

INTRODUCTION: This study was conducted to evaluate the clinical outcome of the treatment of type C pilon fractures by using an external fixator combined with limited open reduction and absorbable internal fixation. PATIENTS AND METHODS: Twenty-five type C pilon fractures, including 4 open fractures, were included in this retrospective study. The procedure of first-stage manipulation and external fixation spanning the ankle joint was conducted as early as possible. For the second stage, the tibial and fibular fractures were reduced and fixed with absorbable screws or rods through a limited incision. Clinical and radiographic evaluations were performed. The American Orthopaedic Foot & Ankle Society score (AOFAS) was obtained for evaluation of function. Twenty-one patients were followed postoperatively for a minimum of 18 months. RESULTS: The mean time of union was 4.8 months. Delayed union of the distal tibia occurred in 1 patient. Minor infection occurred in 8 patients and deep infection in 1 patient. No skin necrosis, malunion, loss of reduction, nonunion, or fixation failure was observed during the follow-up period. No hardware removal was needed, nor was adverse tissue reaction to the implants observed. An excellent or good AOFAS outcome was obtained in 81% (17/21) of the patients. CONCLUSIONS: External fixator combined with limited open reduction and absorbable internal fixation was a reliable treatment for closed and open AO/OTA type C pilon fractures of the distal tibia.

Chemical Constituents from Mycelia of Lepista sordida (Agaricomycetes) and Their ABTS Radical Scavenging Activity.

Lepista sordida is an edible mushroom possessing high nutritional value and high medicinal value. The artificial cultivation technology of L. sordida made a breakthrough and has been popularized in Yunnan, Guizhou, Sichuan province with good economic benefits. The secondary metabolites were investigated from ethyl EtOAc (acetate extract) of solid cultures of L. sordida. Silica gel column chromatography, semi-preparation HPLC, recrystallization, and medium pressure column chromatography were applied to obtain 15 compounds. Nine compounds were first isolated from genus Lepista and 11 compounds were first isolated from species L. sordida. Moreover, compounds 13 and 14 exhibited strong scavenging activity of ABTS.

MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells.

BACKGROUND: The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells (PSCs) into osteoblasts or chondrocytes; however, the underlying mechanisms remain unclear. AIM: To determine the effect of hypoxia on PSCs, and the expression of microRNA-584-5p (miR-584-5p) and RUNX family transcription factor 2 (RUNX2) in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxia-induced osteogenic differentiation of PSCs. METHODS: In this study, we isolated primary mouse PSCs and stimulated them with hypoxia, and the characteristics and functional genes related to PSC osteogenic differentiation were assessed. Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation. RESULTS: Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules, intracellular calcium ion levels, and alkaline phosphatase (ALP) activity in PSCs. Osteogenic differentiation-related factors such as RUNX2, bone morphogenetic protein 2, hypoxia-inducible factor 1-alpha, and ALP were upregulated; in contrast, miR-584-5p was downregulated in these cells. Furthermore, upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation. RUNX2 was the target gene of miR-584-5p, antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation. CONCLUSION: Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.

Identification of acetylshikonin as a novel tubulin polymerization inhibitor with antitumor activity in human hepatocellular carcinoma cells.

Background: Microtubules are attractive targets for anticancer drugs. However, the microtubule-targeting agents (MTAs) currently in clinical use exhibit inevitable drug resistance. Therefore, there is an urgent need to discover novel MTAs for the clinical treatment of cancer. Methods: Bioactive compounds extracted from Lithospermum erythrorhizon were assessed for in vitro anti-proliferative activities against a panel of human cancer cell lines using cell counting kit-8 (CCK-8) assay. Tubulin polymerization inhibition assay, colchicine competitive binding site assay, and immunofluorescence were used to validate the tubulin inhibition effect of acetylshikonin. Flow cytometry, Hoechst staining, and caspase-3 activity evaluation were performed to assess cell cycle arrest and cell apoptosis. 5,5',6,6'-tetrachloro-1,1',3,3'-tetramethylbenzimidazolylcarbocyanine iodide (JC-1) staining and dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining were used to evaluate mitochondrial membrane potential (MMP) and reactive oxygen species (ROS), respectively. Results: Acetylshikonin exhibited potent anti-proliferative activities against a panel of human cancer cell lines (IC50 values: 1.09-7.26 µM) and displayed comparable cytotoxicity against several drug-resistant cell lines. Further mechanism studies revealed that acetylshikonin induced cell cycle arrest of MHCC-97H cells at G2/M phase, and significantly promoted apoptosis marked by a collapse of MMP and abnormal ROS accumulation. Conclusions: In this study, acetylshikonin was identified as MTA against hepatocellular carcinoma and can serve as a promising lead compound for further development of anti-cancer drug, underscoring its potential clinical significance.

Flexible Ultrasound Transducer With Embedded Optical Shape Sensing Fiber for Biomedical Imaging Applications.

Flexible ultrasound transducers (FUTs), capable of conforming to irregular surfaces, have become a research hotspot in the field of medical imaging. With these transducers, high-quality ultrasound images can be obtained only if strict design criteria are fulfilled. Moreover, the relative positions of array elements must be determined, which are important for ultrasound beamforming and image reconstruction. These two major characteristics present great challenges to the design and fabrication of FUTs compared to that for traditional rigid probes. In this study, an optical shape-sensing fiber was embedded into a 128-element flexible linear array transducer to acquire the real-time relative positions of array elements to produce high-quality ultrasound images. Minimum concave and convex bend diameters of approximately 20 and 25 mm, respectively, were achieved. The transducer was flexed 2000 times, and yet no obvious damage was observed. Stable electrical and acoustic responses confirmed its mechanical integrity. The developed FUT exhibited an average center frequency of 6.35 MHz, and average -6-dB bandwidth of 69.2%. The array profile and element positions measured by the optic shape-sensing system were instantly transferred to the imaging system. Phantom experiments for both spatial resolution and contrast-to-noise ratio proved that FUTs can maintain satisfactory imaging capability despite bending to sophisticated geometries. Finally, color Doppler images and Doppler spectra of the peripheral arteries of healthy volunteers were obtained in real time.

In vivo ocular microvasculature imaging in rabbits with 3D ultrasound localization microscopy.

Morphological and hemodynamic changes in the ocular vasculature are important signs of various ocular diseases. The evaluation of the ocular microvasculature with high resolution is valuable in comprehensive diagnoses. However, it is difficult for current optical imaging techniques to visualize the posterior segment and retrobulbar microvasculature due to the limited penetration depth of light, particularly when the refractive medium is opaque. Thus, we have developed a 3D ultrasound localization microscopy (ULM) imaging method to visualize the ocular microvasculature in rabbits with micron-scale resolution. We used a 32 × 32 matrix array transducer (center frequency: 8 MHz) with a compounding plane wave sequence and microbubbles. Block-wise singular value decomposition spatiotemporal clutter filtering and block-matching 3D denoising were implemented to extract the flowing microbubble signals at different imaging depths with high signal-to-noise ratios. The center points of microbubbles were localized and tracked in 3D space to achieve the micro-angiography. The in vivo results demonstrate the ability of 3D ULM to visualize the microvasculature of the eye in rabbits, where vessels down to 54 µm were successfully revealed. Moreover, the microvascular maps indicated the morphological abnormalities in the eye with retinal detachment. This efficient modality shows potential for use in the diagnosis of ocular diseases.

In-vivo programmable acoustic manipulation of genetically engineered bacteria.

Acoustic tweezers can control target movement through the momentum interaction between an acoustic wave and an object. This technology has advantages over optical tweezers for in-vivo cell manipulation due to its high tissue penetrability and strong acoustic radiation force. However, normal cells are difficult to acoustically manipulate because of their small size and the similarity between their acoustic impedance and that of the medium. In this study, we use the heterologous expression of gene clusters to generate genetically engineered bacteria that can produce numerous sub-micron gas vesicles in the bacterial cytoplasm. We show that the presence of the gas vesicles significantly enhances the acoustic sensitivity of the engineering bacteria, which can be manipulated by ultrasound. We find that by employing phased-array-based acoustic tweezers, the engineering bacteria can be trapped into clusters and manipulated in vitro and in vivo via electronically steered acoustic beams, enabling the counter flow or on-demand flow of these bacteria in the vasculature of live mice. Furthermore, we demonstrate that the aggregation efficiency of engineering bacteria in a tumour is improved by utilizing this technology. This study provides a platform for the in-vivo manipulation of live cells, which will promote the progress of cell-based biomedical applications.

Effect of theophylline on prevention of contrast-induced acute kidney injury: a meta-analysis of randomized controlled trials.

BACKGROUND: Whether treatment with adenosine receptor antagonists such as theophylline can prevent contrast-induced acute kidney injury (AKI) remains controversial. STUDY DESIGN: We conducted a meta-analysis of randomized controlled trials using MEDLINE (1966 to July 2011), EMBASE (1980 to July 2011), Web of Science (1986 to July 2011), and the Cochrane Central Register of Controlled Trials (1996 to July 2011), without language restriction. SETTING & POPULATION: Patients undergoing contrast procedures. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials assessing adenosine antagonists versus control for prevention of contrast-induced AKI. INTERVENTION: Adenosine antagonists with or without N-acetylcysteine versus control with or without N-acetylcysteine. OUTCOMES: Contrast-induced AKI, change in serum creatinine level, requirement of dialysis, and in-hospital mortality. RESULTS: 16 trials (1,412 participants) were included. Theophylline significantly decreased the risk of contrast-induced AKI (13 trials, 1,222 patients; risk ratio, 0.48; 95% CI, 0.26-0.89; P = 0.02; I(2) = 45%) and had a protective effect on the absolute change in serum creatinine concentration (13 trials, 1,170 patients; standardized mean difference, -0.31 mg/dL; 95% CI, -0.50 to -0.11; P = 0.002; I(2) = 60%). Meta-regression showed a significant relation between the relative risk of contrast nephropathy and baseline serum creatinine level or Jadad score. No clear effects of treatment on risk of dialysis and in-hospital mortality were identified. LIMITATIONS: Power to assess clinical end points was limited. CONCLUSIONS: Theophylline treatment significantly reduced the incidence of contrast-induced AKI and had a modest improvement on kidney function after contrast exposure in the general population. However, beneficial effects of theophylline were not observed in patients with high baseline creatinine values (serum creatinine ≥1.5 mg/dL). In addition, the long-term effect of this agent on more clinically important outcomes was not established. Future large-scale high-quality multicenter trials in participants with different underlying risks of contrast-induced AKI and that incorporate the evaluation of clinically relevant outcomes are required.

QFD-Based Research on Sustainable User Experience Optimization Design of Smart Home Products for the Elderly: A Case Study of Smart Refrigerators.

In the current situation of global aging, the current market shortage of age-appropriate smart home products and the recent epidemic have led to greater isolation of the elderly, seriously affecting their physical and mental health. In order to optimize the sustainable user experience of the elderly when using smart home products, this paper proposes a research method based on Quality Function Deployment (QFD) for the optimal design of user experience of smart home products for the elderly, taking the design of age-appropriate home smart refrigerators as an example. Firstly, based on the results of market research and user interviews, the requirements of smart refrigerators for the elderly are screened and integrated, and the Kano model is used to prioritize these needs, resulting in the identification of important features needed in smart refrigerators for the elderly. Secondly, based on QFD, user requirements are transformed into design requirements, and a quality house model is established to ascertain the degree of importance of each design requirement through user ratings so as to obtain the key requirements as the theoretical basis for the solution design. Finally, optional solutions are generated for concept evaluation based on PUGH concept selection, comparing the advantages and disadvantages of the solutions and recombining them into an evaluation to determine the best solution. The quantitative evaluation of the four solutions reveals that Solution A has the highest score of 117.358, followed by Solution D with 113.259, Solution B with 96.415, and Solution C with 85.511, which is the lowest. The scoring allows the best design solution to be selected and applied to product development. The results show that the introduction of the Kano model and PUGH concept selection into QFD can be effectively used as a research method for optimizing the user experience of smart refrigerators for the elderly, and a corresponding design strategy for sustainable user experience optimization is proposed. The method and strategy provide guidance for the innovative design of new smart home products.

3D Acoustic Manipulation of Living Cells and Organisms Based On 2D Array.

Flexible manipulation techniques for living cells and organisms are extremely useful tools for fundamental biomedical and life science research. Acoustic tweezers, which permit non-contact, label-free manipulation, are particularly suited to micromanipulation tasks as they provide a large acoustic radiation force and can be applied in various media. Here, we describe the design and fabrication of a 3 MHz, 64-element (8 × 8), 2D planar ultrasound array that realizes the multidimensional translation, rotation, orientation, and levitation of living cells and organisms. The focusing vortex and twin fields are generated using the holographic acoustic elements framework method. We demonstrate that the eggs and larvae of brine shrimp can be translated along a preset trajectory by controlling the central position of the vortex. By multiplexing counterclockwise vortices, clockwise vortices, and twin trap fields in a time sequence, the rotation direction of the shrimp eggs can be switched in real time, while non-spherical larvae can be reoriented. Moreover, the reflection of the acoustic beam can lift eggs and larvae from the bottom of the culture dish and further manipulate them in the vertical and horizontal directions. Additionally, we present quantitative analyses of the shrimp-egg rotation frequency with respect to the focal depths, topological charges of the vortex, and excitation voltages. These results indicate that acoustic tweezers based on 2D matrix arrays can realize complex and selective manipulation of living cells and organisms, thereby demonstrating their value for advancing research in the fields of cell assembly, tissue engineering, and micro-robot driving.

LINC00665 affects the malignant biological behavior of ovarian cancer via the miR-148b-3p/KLF5.

This study investigated the expression and clinical significance of long intergenic noncoding RNA 00665 (LINC00665) in ovarian cancer (OC), as well as its effect on the malignant biological behavior of OC cells. The expression of LINC00665, miR-148b-3p, and Krüppel-like factor 5 (KLF5) in OC tissues and cells were determined by RT-qPCR. Western blot was used to detect the protein expression of KLF5. The expression patterns of LINC00665 in nuclear and cytoplasm fractions were undertaken using RT-qPCR. In addition, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, the interactions between LINC00665 and miR-148b-3p and between miR-148b-3p and KLF5 were verified by the luciferase reporter assay, and the correlations among these three genes were analyzed. LINC00665 expression was upregulated both in OC cell lines and tissues. Si-LINC00665 inhibited cell proliferation, invasion, and migration and induced apoptosis to a certain extent. The subcellular fraction assay revealed LINC00665 to be located mainly in the cytoplasm. miR-148b-3p was a target of LINC00665, and KLF5 was directly targeted by miR-148b-3p. Si-LINC00665 inhibited KLF5 expression, miR-148b-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited LINC00665 expression. Interestingly, the expression of LINC00665 was reversely associated with miR-148b-3p expression but positively correlated with KLF5. Furthermore, miR-148b-3p expression was negatively correlated with KLF5. In addition, si-KLF5 inhibited the malignant biological behavior of OC cells, whereas miR-148b-3p inhibitor had the opposite effect. Most importantly, the si-LINC00665 could reverse the promotion effect of the miR-148b-3p inhibitor on the malignant biological behavior of OC cells. LINC00665 can be used as an effective prognostic indicator of OC, which has the potential to be a new therapeutic target.

Design and Fabrication of a High-Frequency Microconvex Array Transducer for Small Animals Imaging.

High-frequency convex array transducer, featuring both high spatial resolution and wide field of view, has been successfully developed for ophthalmic imaging. To further expand its application range to small animals' imaging, this work develops a high-frequency microconvex array transducer possessing smaller aperture size and wider scanning angle. This transducer featured 128 array elements arranged in a curvilinear 2-2 piezoelectric composite configuration, yielding a maximum view angle of 97.8°. The array was composed of two front matching layers, a nonconductive backing layer, and a customized flexible circuit that electrically connected array elements to coaxial cables. The center frequency and the -6-dB fractional bandwidth were about 18.14 MHz and 69.15%, respectively. The image of a tungsten wire phantom resulted in approximately 62.9- [Formula: see text] axial resolution and 121.3- [Formula: see text] lateral resolution. The image of the whole kidney of a rat as well as its internal arteries was acquired in vivo, demonstrating the imaging capability of the proposed high-frequency microconvex array transducers for small animals' imaging applications.