CD133-targeted multifunctional nanomicelles for dual-modality imaging and synergistic high-intensity focus ultrasound (HIFU) ablation on pancreatic cancer in nude mice.

Pancreatic cancer is an aggressive and highly fatal malignant tumor. Recent studies have shown that cancer stem cells (CSCs) play an important role in resisting current therapeutic modalities. Furthermore, CD133 is highly expressed in CSCs. High-intensity focused ultrasound (HIFU) is a promising non-invasive therapeutic strategy for unresectable pancreatic cancers. In our study, we synthesized targeted CD133 organosilane nanomicelles by encapsulating perfluorohexane (PFH). The CD133 antibody on the surface could specifically bind to CD133-positive pancreatic cancer cells and selectively concentrate in pancreatic cancer tumor tissues. PFH was introduced to improve the ablation effect of HIFU due to its liquid-gas phase transition properties. By combining with the dorsal skinfold window chamber model (DSWC) of pancreatic cancer in nude mice, multiphoton fluorescence microscopy was used to evaluate the targeting effect of nanomicelles on pancreatic cancer tumor tissue. These multifunctional nanomicelles synergistically affected HIFU treatment of pancreatic cancer, providing an integrated research platform for diagnosing and treating pancreatic cancer with HIFU.

Primary pulmonary meningioma and minute pulmonary meningothelial-like nodules: Rare pulmonary nodular lesions requiring more awareness in clinical practice.

In this editorial, we comment on an article by Ruan et al published in a recent issue of the World Journal of Clinical Case. Pulmonary meningothelial proliferative lesions, including primary pulmonary meningiomas, minute pulmonary meningothelial-like nodules, and metastatic pulmonary meningiomas are rare pulmonary lesions. These lesions are difficult to differentiate from lung cancers based on clinical and imaging manifestations. Herein, we briefly introduce the clinical, imaging, and pathological characteristics of these lesions and discuss their pathogenesis to strengthen the current understanding of pulmonary meningothelial proliferative lesions in clinical diagnosis and therapy.

Response of fine particulate matter and ozone concentrations to meteorology and anthropogenic precursors over the "2+26" cities of northern China.

Analyzing the influencing factors of fine particulate matter and ozone formation and identifying the coupling relationship between the two are the basis for implementing the synergistic pollutants control. However, the current research on the synergistic relationship between the two still needs to be further explored. Using the Geodetector model, we analyzed the effects of meteorology and emissions on fine particulate matter and ozone concentrations over the "2 + 26" cities at multiple timescales, and also explored the coupling relationship between the two pollutants. Fine particulate matter concentrations showed overall decreasing trends on inter-season and inter-annual scale from 2015 to 2021, whereas ozone concentrations showed overall increasing trends. While ozone concentrations displayed an inverted U-shaped distribution from month to month, fine particulate matter concentrations displayed a U-shaped fluctuation. On inter-annual scale, climatic factors, with planet boundary layer height as the main determinant, have higher effects for both pollutants than human precursors. In summer and autumn, sunshine duration had the most influence on fine particulate matter, while planet boundary layer height was the greatest factor in winter. Fine particulate matter is the leading impacting factor on ozone concentrations in summer, and there were positive associations between them on both annual and seasonal scale. The impact of nitrogen oxides and volatile organic compounds for both pollutants concentrations varied significantly between seasons. The two pollutants concentration were enhanced by the interactions between the various components. On inter-annual scale, interactions between the planet boundary layer height and other factors dominated the concentrations of the two pollutants, whereas in summer, interactions between fine particulate matter and other factors dominated the concentrations of ozone. The study has implications for the treatment of atmospheric pollution in China and other nations and can serve as an important reference for the creation of integrated atmospheric pollution regulation policies over the "2 + 26" cities.

Release of extracellular vesicles triggered by low-intensity pulsed ultrasound: immediate and delayed reactions.

Previous studies have shown that ultrasound may stimulate the release of extracellular vesicles, improving the efficiency of tumor detection. However, it is unclear whether ultrasonic stimulation affects the distribution of extracellular vesicles, and the duration of such stimulation release has not been extensively studied. In this study, we stimulated cells with low-intensity pulsed ultrasound and used liposomes containing black hole quenchers to simulate natural extracellular vesicles, confirming that ultrasound has a destructive effect on vesicles and thus affects particle size distribution. Furthermore, we used proteomics technology to examine the protein expression profile of small vesicles and discovered that the expression of proteins involved in exosome biogenesis was down-regulated. We then looked into the regulation of the actin cytoskeleton and endocytosis pathways, which are required for intracellular vesicle transport, and discovered that ultrasound might induce F-actin depolymerization. The intracellular transport of the cation-independent mannose-6-phosphate receptor (CI-MPR) in the trans-Golgi network (TGN) and the amount of Rab7a protein were proportional to the culture time after LIPUS treatment.

Mixing Performance Analysis and Optimal Design of a Novel Passive Baffle Micromixer.

Micromixers, as crucial components of microfluidic devices, find widespread applications in the field of biochemistry. Due to the laminar flow in microchannels, mixing is challenging, and it significantly impacts the efficiency of rapid reactions. In this study, numerical simulations of four baffle micromixer structures were carried out at different Reynolds numbers (Re = 0.1, Re = 1, Re = 10, and Re = 100) in order to investigate the flow characteristics and mixing mechanism under different structures and optimize the micromixer by varying the vertical displacement of the baffle, the rotation angle, the horizontal spacing, and the number of baffle, and by taking into account the mixing intensity and pressure drop. The results indicated that the optimal mixing efficiency was achieved when the baffle's vertical displacement was 90 µm, the baffle angle was 60°, the horizontal spacing was 130 µm, and there were 20 sets of baffles. At Re = 0.1, the mixing efficiency reached 99.4%, and, as Re increased, the mixing efficiency showed a trend of, first, decreasing and then increasing. At Re = 100, the mixing efficiency was 97.2%. Through simulation analysis of the mixing process, the structure of the baffle-type micromixer was effectively improved, contributing to enhanced fluid mixing efficiency and reaction speed.

Time-dependent effects of acoustic trauma and tinnitus on extracellular levels of amino acids in the inferior colliculus of rats.

Chronic tinnitus is a debilitating condition with very few management options. Acoustic trauma that causes tinnitus has been shown to induce neuronal hyperactivity in multiple brain areas in the auditory pathway, including the inferior colliculus. This neuronal hyperactivity could be attributed to an imbalance between excitatory and inhibitory neurotransmission. However, it is not clear how the levels of neurotransmitters, especially neurotransmitters in the extracellular space, change over time following acoustic trauma and the development of tinnitus. In the present study, a range of amino acids were measured in the inferior colliculus of rats during acoustic trauma as well as at 1 week and 5 months post-trauma using in vivo microdialysis and high-performance liquid chromatography. Amino acid levels in response to sound stimulation were also measured at 1 week and 5 months post-trauma. It was found that unilateral exposure to a 16 kHz pure tone at 115 dB SPL for 1 h caused immediate hearing loss in all the animals and chronic tinnitus in 58 % of the animals. Comparing to the sham condition, extracellular levels of GABA were significantly increased at both the acute and 1 week time points after acoustic trauma. However, there was no significant difference in any of the amino acid levels measured between sham, tinnitus positive and tinnitus negative animals at 5 months post-trauma. There was also no clear pattern in the relationship between neurochemical changes and sound frequency/acoustic trauma/tinnitus status, which might be due to the relatively poorer temporal resolution of the microdialysis compared to electrophysiological responses.

Temperature and Twist Sensor Based on the Sagnac Interferometer with Long-Period Grating in Polarization-Maintaining Fiber.

We utilized a CO2 laser to carve long-period fiber gratings (LPFGs) on polarization-maintaining fibers (PMFs) along the fast and slow axes. Based on the spectra of LPFGs written along two different directions, we found that when LPFG was written along the fast axis, the spectrum had lower insertion loss and fewer side lobes. We investigated the temperature and twist characteristics of the embedded structure of the LPFG and Sagnac loop and ultimately obtained a temperature sensitivity of -0.295 nm/°C and a twist sensitivity of 0.87 nm/(rad/m) for the LPFG. Compared to the single LPFG, the embedded structure of the LPFG and Sagnac loop demonstrates a significant improvement in temperature and twist sensitivities. Additionally, it also possesses the capability to discern the direction of the twist. The embedded structure displays numerous advantages, including easy fabrication, low cost, good robustness, a wide range, and high sensitivity. These features make it highly suitable for applications in structural health monitoring and other related fields.

Combined Assessment of 2-D Ultrasound and Real-Time Shear Wave Elastography of Low-Intensity Pulsed Ultrasound Therapy Efficacy in Rabbits with Achilles Tendinopathy.

OBJECTIVE: Low-intensity pulsed ultrasound (LIPUS) has been gradually used to treat Achilles tendinopathy. However, there are limited non-invasive and efficient instruments for monitoring LIPUS efficacy in Achilles tendinopathy. The purpose of this study was to assess the therapeutic effectiveness of LIPUS after Achilles tendinopathy by 2-D ultrasound and real-time shear wave elastography (SWE). METHODS: Ninety New Zealand white rabbits were divided into control, sham and LIPUS groups after tendinopathy modeling. On days 1, 4, 7, 14 and 28, the Achilles tendon thickness and SWE Young's modulus on the long axis were measured. The tissues of the Achilles tendon were then evaluated histologically. RESULTS: The mean SWE values increased while the average thickness and histologic scores decreased, especially in the LIPUS group (9.5% and 80.7% on day 28, respectively). The SWE values in the LIPUS group were significantly lower than those in the control group on day 1 (121.0 kPa vs. 177.6 kPa) and peaked on day 7 (173.7 kPa, p < 0.001). By day 28, the SWE value had approached that of the control (191.2 kPa vs. 192.4 kPa), and had been significantly higher than that in the sham group since day 7. SWE values and histologic scores were correlated (r = -0.792, p < 0.01). The average thickness decreased in the three groups but did not differ significantly. CONCLUSION: Two-dimensional ultrasound is beneficial to the diagnosis of Achilles tendinopathy. SWE could quantify changes in Achilles tendon stiffness non-invasively during LIPUS treatment, enabling the study of early Achilles tendon healing after LIPUS treatment.

ITGB2-ICAM1 axis promotes liver metastasis in BAP1-mutated uveal melanoma with retained hypoxia and ECM signatures.

PURPOSE: Uveal melanoma (UM) with BAP1 inactivating mutations has a high risk of metastasis, but the mechanism behind BAP1 deficiency driving UM metastasis is unknown. METHODS: We analyzed the single-cell RNA sequencing (scRNA-Seq) data comprised primary and metastatic UM with or without BAP1 mutations (MUTs) to reveal inter- and intra-tumor heterogeneity among different groups. Then, an immune-competent mouse liver metastatic model was used to explore the role of ITGB2-ICAM1 in BAP1-associated UM metastasis. RESULTS: Cluster 1 tumor cells expressed high levels of genes linked to tumor metastasis, such as GDF15, ATF3, and CDKN1A, all of which are associated with poor prognosis. The strength of communication between terminally exhausted CD8+ T cells and GDF15hiATF3hiCDKN1Ahi tumor cells was enhanced in BAP1-mutated UM, with CellChat analysis predicting strong ITGB2-ICAM1 signaling between them. High expression of either ITGB2 or ICAM1 was a worse prognostic indicator. Using an immune-competent mouse liver metastatic model, we indicated that inhibiting either ICAM1 or ITGB2 prevented liver metastasis in the BAP1-mutated group in vivo. The inhibitors primarily inhibited hypoxia- and ECM-related pathways indicated by changes in the expression of genes such as ADAM8, CAV2, ENO1, PGK1, LOXL2, ITGA5, and VCAN. etc. CONCLUSION: This study suggested that the ITGB2-ICAM1 axis may play a crucial role for BAP1-associated UM metastasis by preserving hypoxia- and ECM- related signatures, which provide a potential strategy for preventing UM metastasis in patients with BAP1 mutation.

A high sensitivity cross-capacitive sensor for water droplets and bubble detection in hydraulic oil.

The presence of moisture and air in hydraulic oil will seriously affect the reliability of machines. This paper proposes a new cross-capacitive oil pollution detection sensor, which is based on the Thompson and Lampard theorem. The sensing unit consists of four identical copper electrodes with infinitesimally small gaps. The sensor can effectively distinguish water droplets and air bubble pollutants mixed in the oil through the pulse direction of the signal. Compared with traditional capacitive sensors, the sensor has a significant improvement in detection accuracy and detection throughput. In this paper, the relationship between the cross-capacitance value with the dielectric constant and the frequency in an alternating electric field was deduced, and the best excitation frequency was chosen as 1.9 MHz. Experiments show that the sensor can effectively detect water droplets of 140-160 µm and bubbles of 170-190 µm and has good linearity for detecting water droplets and air bubbles of different sizes. The sensor provides a new method for machine condition monitoring of hydraulic systems.

Integrative landscape analysis of prognostic model biomarkers and immunogenomics of disulfidptosis-related genes in breast cancer based on LASSO and WGCNA analyses.

BACKGROUND: Disulfidptosis is a novel type of programmed cell death. However, the value of disulfidptosis-related genes (DRGs) in the prediction of breast cancer prognosis is unclear. METHODS: RNA-seq data of 1231 patients, together with information on patient clinical characteristics and prognosis, were downloaded from TCGA. DRGs were identified between cancerous and non-cancerous tissues. The LASSO algorithm was used to assign half of the samples to the training set. Risk scores were used for construction of a prognostic model for risk stratification and prognosis prediction, and the clinical applicability was examined using a line diagram. The relationships between risk scores, immune cell infiltration, molecular subtypes, and responses to immunotherapy and chemotherapy were examined. RESULTS: We identified and obtained four DRG-related prognostic lncRNAs (AC009097.2, AC133552.5, YTHDF3-AS1, and AC084824.5), which were used for establishing the risk model. Longer survival was associated with low risk. The DRG-associated lncRNAs were found to independently predict patient prognosis. The AUCs under the ROCs for one-, three-, and 5-year survival in the training cohort were 0.720, 0.687, and 0.692, respectively. The model showed that the high-risk patients had reduced overall survival as well as high tumor mutation burdens. Furthermore, high-risk patients showed increased sensitivity to therapeutic drugs, including docetaxel, paclitaxel, and oxaliplatin. CONCLUSION: The risk score model was effective for predicting both prognosis and sensitivity to therapeutic drugs, suggesting its possible usefulness for the management of patients with breast cancer.

High-Sensitivity Temperature Sensor Based on Fiber Fabry-Pérot Interferometer with UV Glue-Filled Hollow Capillary Fiber.

Optical fiber Fabry-Pérot (FP) interferometer sensors have long been the focus of researchers in sensing applications because of their simple light path, low cost, compact size and convenient manufacturing methods. A miniature and highly sensitive optic fiber temperature sensor using an ultraviolet glue-filled FP cavity in a hollow capillary fiber is proposed. The sensor is fabricated by fusion splicing a single-mode fiber with a hollow capillary fiber, which is filled with ultraviolet glue to form a FP cavity. The sensor has a good linear response in the temperature testing and high-temperature sensitivity, which can be increased with the length of the FP cavity. The experimental results show that the temperature sensitivity reaches 1.174 nm/°C with a high linear response in the range of 30-60 °C. In addition, this sensor is insensitive to pressure and can be highly suitable for real-time water temperature monitoring for ocean research. The proposed ultraviolet glue-filled structure has the advantages of easy fabrication, high-temperature sensitivity, low cost and an arbitrary length of capillary, which has broad application prospects for marine survey technology, biological diagnostics and environmental monitoring.

Molecular mechanisms of immunotherapy resistance in triple-negative breast cancer.

The emergence of immunotherapy has profoundly changed the treatment model for triple-negative breast cancer (TNBC). But the heterogeneity of this disease resulted in significant differences in immunotherapy efficacy, and only some patients are able to benefit from this therapeutic modality. With the recent explosion in studies on the mechanism of cancer immunotherapy drug resistance, this article will focus on the processes of the immune response; summarize the immune evasion mechanisms in TNBC into three categories: loss of tumor-specific antigen, antigen presentation deficiency, and failure to initiate an immune response; together with the aberrant activation of a series of immune-critical signaling pathways, we will discuss how these activities jointly shape the immunosuppressive landscape within the tumor microenvironment. This review will attempt to elucidate the molecular mechanism of drug resistance in TNBC, identify potential targets that may assist in reversing drug resistance, and lay a foundation for research on identifying biomarkers for predicting immune efficacy and selection of breast cancer populations that may benefit from immunotherapy.

Targeting the Limbic System: Insights into Its Involvement in Tinnitus.

Tinnitus is originally derived from the Latin verb tinnire, which means "to ring". Tinnitus, a complex disorder, is a result of sentient cognizance of a sound in the absence of an external auditory stimulus. It is reported in children, adults, and older populations. Patients suffering from tinnitus often present with hearing loss, anxiety, depression, and sleep disruption in addition to a hissing and ringing in the ear. Surgical interventions and many other forms of treatment have been only partially effective due to heterogeneity in tinnitus patients and a lack of understanding of the mechanisms of tinnitus. Although researchers across the globe have made significant progress in understanding the underlying mechanisms of tinnitus over the past few decades, tinnitus is still deemed to be a scientific enigma. This review summarises the role of the limbic system in tinnitus development and provides insight into the development of potential target-specific tinnitus therapies.

Vestibular modulation of the tail of the rat striatum.

Fragmented and piecemeal evidence from animal and human studies suggests that vestibular information is transmitted to the striatum, a part of the basal ganglia that degenerates in Parkinson's Disease. Nonetheless, surprisingly little is known about the precise effects of activation of the vestibular system on the striatum. Electrophysiological studies have yielded inconsistent results, with many studies reporting only sparse responses to vestibular stimulation in the dorsomedial striatum. In this study, we sought to elucidate the effects of electrical stimulation of the peripheral vestibular system on electrophysiological responses in the tail of the rat striatum, a newly discovered region for sensory input. Rats were anaesthetised with urethane and a bipolar stimulating electrode was placed in the round window in order to activate the peripheral vestibular system. A recording electrode was positioned in the tail of the striatum. Local field potentials (LFPs) were recorded ipsilaterally and contralaterally to the stimulation using a range of current parameters. In order to confirm that the vestibular system was activated, video-oculography was used to monitor vestibular nystagmus. At current amplitudes that evoked vestibular nystagmus, clear triphasic LFPs were evoked in the bilateral tail of the striatum, with the first phase of the waveform exhibiting latencies of less than 22 ms. The LFP amplitude increased with increasing current amplitude (P ≤ 0.0001). In order to exclude the possibility that the LFPs were evoked by the activation of the auditory system, the cochlea was surgically lesioned in some animals. In these animals the LFPs persisted despite the cochlear lesions, which were verified histologically. Overall, the results obtained suggest that there are vestibular projections to the tail of the striatum, which could possibly arise from projections via the vestibular nucleus or cerebellum and the parafasicular nucleus of the thalamus.

Quantifying hydrological-ecological response relationships based on zooplankton index of biotic integrity and comprehensive habitat quality index - A case study of typical rivers in Xi'an, China.

With the accelerated development of urbanization, rivers in urban areas have become the most closely synergized water ecosystem between human activities and natural processes. To achieve the restoration goal of using hydrological regime change-ecological response relationship to advance the sustainable development of regulated river ecosystems, this study collected ecohydrological data at four tributaries of the Wei River system (Ba, Chan, Feng, and Hei Rivers) at a total of 24 stations in October 2020 and June 2021. Taking ecological flow as hydrological parameter and zooplankton as indicator organism, combined with habitat data scored on-site, the indicator system of zooplankton index of biological integrity and comprehensive habitat quality index was established to explore the hydrological-ecological response relationship in a multi-dimensional way. The results showed that during the ebb stage, the ecological health of the Feng River was better overall, with an average ecological flow value of 267.09 ± 348.62. The ecological health of the Hei River was the worst, with an average ecological flow value of 37.80 ± 38.80. During the abundant water period, the ecological health of the Chan River was optimal with an average ecological flow value of 189.25 ± 190.10, while the ecological health of the Hei River remained unimproved, but the average ecological flow value increased by 283.12 ± 197.76. There was a clear negative correlation relationship between the comprehensive habitat quality index and ecological flow. The correlation between zooplankton index of biological integrity and ecological flows is extremely strong and threshold values exist, but there is strong heterogeneity in the interaction of disturbance factors across water systems, which may not provide a predictable response to flow changes. This study aims to provide a case reference for flow management in watersheds that also lack long-time series hydrological data and to contribute new thinking to the wide application of the hydrological-ecological response relationship.

Progress of photoacoustic imaging combined with targeted photoacoustic contrast agents in tumor molecular imaging.

Molecular imaging visualizes, characterizes, and measures biological processes at the molecular and cellular level. In oncology, molecular imaging is an important technology to guide integrated and precise diagnosis and treatment. Photoacoustic imaging is mainly divided into three categories: photoacoustic microscopy, photoacoustic tomography and photoacoustic endoscopy. Different from traditional imaging technology, which uses the physical properties of tissues to detect and identify diseases, photoacoustic imaging uses the photoacoustic effect to obtain the internal information of tissues. During imaging, lasers excite either endogenous or exogenous photoacoustic contrast agents, which then send out ultrasonic waves. Currently, photoacoustic imaging in conjunction with targeted photoacoustic contrast agents is frequently employed in the research of tumor molecular imaging. In this study, we will examine the latest advancements in photoacoustic imaging technology and targeted photoacoustic contrast agents, as well as the developments in tumor molecular imaging research.

Deffini: A family-specific deep neural network model for structure-based virtual screening.

Deep learning-based virtual screening methods have been shown to significantly improve the accuracy of traditional docking-based virtual screening methods. In this paper, we developed Deffini, a structure-based virtual screening neural network model. During training, Deffini learns protein-ligand docking poses to distinguish actives and decoys and then to predict whether a new ligand will bind to the protein target. Deffini outperformed Smina with an average AUC ROC of 0.92 and AUC PRC of 0.44 in 3-fold cross-validation on the benchmark dataset DUD-E. However, when tested on the maximum unbiased validation (MUV) dataset, Deffini achieved poor results with an average AUC ROC of 0.517. We used the family-specific training approach to train the model to improve the model performance and concluded that family-specific models performed better than the pan-family models. To explore the limits of the predictive power of the family-specific models, we constructed Kernie, a new protein kinase dataset consisting of 358 kinases. Deffini trained with the Kernie dataset outperformed all recent benchmarks on the MUV kinases, with an average AUC ROC of 0.745, which highlights the importance of quality datasets in improving the performance of deep neural network models and the importance of using family-specific models.

Sustainable valorization of asphaltenes via flash joule heating.

The refining process of petroleum crude oil generates asphaltenes, which poses complicated problems during the production of cleaner fuels. Following refining, asphaltenes are typically combusted for reuse as fuel or discarded into tailing ponds and landfills, leading to economic and environmental disruption. Here, we show that low-value asphaltenes can be converted into a high-value carbon allotrope, asphaltene-derived flash graphene (AFG), via the flash joule heating (FJH) process. After successful conversion, we develop nanocomposites by dispersing AFG into a polymer effectively, which have superior mechanical, thermal, and corrosion-resistant properties compared to the bare polymer. In addition, the life cycle and technoeconomic analysis show that the FJH process leads to reduced environmental impact compared to the traditional processing of asphaltene and lower production cost compared to other FJH precursors. Thus, our work suggests an alternative pathway to the existing asphaltene processing that directs toward a higher value stream while sequestering downstream emissions from the processing.

Optical Fiber Probe Microcantilever Sensor Based on Fabry-Perot Interferometer.

Optical fiber Fabry-Perot sensors have long been the focus of researchers in sensing applications because of their unique advantages, including highly effective, simple light path, low cost, compact size, and easy fabrication. Microcantilever-based devices have been extensively explored in chemical and biological fields while the interrogation methods are still a challenge. The optical fiber probe microcantilever sensor is constructed with a microcantilever beam on an optical fiber, which opens the door for highly sensitive, as well as convenient readout. In this review, we summarize a wide variety of optical fiber probe microcantilever sensors based on Fabry-Perot interferometer. The operation principle of the optical fiber probe microcantilever sensor is introduced. The fabrication methods, materials, and sensing applications of an optical fiber probe microcantilever sensor with different structures are discussed in detail. The performances of different kinds of fiber probe microcantilever sensors are compared. We also prospect the possible development direction of optical fiber microcantilever sensors.