Lymph node targeting strategy using a hydrogel sustained-release system to load effector memory T cells improves the anti-tumor efficacy of anti-PD-1.

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. STATEMENT OF SIGNIFICANCE: F127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.

Time-resolved map of serum metabolome profiling in D-galactose-induced aging rats with exercise intervention.

Exercise, an intervention with wide-ranging effects on the whole body, has been shown to delay aging. Due to aging and exercise as modulator of metabolism, a picture of how exercise delayed D-galactose (D-gal)-induced aging in a time-resolved manner was presented in this paper. The mapping of molecular changes in response to exercise has become increasingly accessible with the development of omics techniques. To explore the dynamic changes during exercise, the serum of rats and D-gal-induced aging rats before, during, and after exercise was analyzed by untargeted metabolomics. The variation of metabolites was monitored to reveal the specific response to D-gal-induced senescence and exercise in multiple pathways, especially the basal amino acid metabolism, including glycine serine and threonine metabolism, cysteine and methionine metabolism, and tryptophan metabolism. The homeostasis was disturbed by D-gal and maintained by exercise. The paper was expected to provide a theoretical basis for the study of anti-aging exercise.

In vitro investigation of stone ablation efficiency, char formation, spark generation, and damage mechanism produced by thulium fiber laser.

To investigate stone ablation characteristics of thulium fiber laser (TFL), BegoStone phantoms were spot-treated in water at various fiber tip-to-stone standoff distances (SDs, 0.5 ~ 2 mm) over a broad range of pulse energy (Ep, 0.2 ~ 2 J), frequency (F, 5 ~ 150 Hz), and power (P, 10 ~ 30 W) settings. In general, the ablation speed (mm3/s) in BegoStone decreased with SD and increased with Ep, reaching a peak around 0.8 ~ 1.0 J. Additional experiments with calcium phosphate (CaP), uric acid (UA), and calcium oxalate monohydrate (COM) stones were conducted under two distinctly different settings: 0.2 J/100 Hz and 0.8 J/12 Hz. The concomitant bubble dynamics, spark generation and pressure transients were analyzed. Higher ablation speeds were consistently produced at 0.8 J/12 Hz than at 0.2 J/100 Hz, with CaP stones most difficult yet COM and UA stones easier to ablate. Charring was mostly observed in CaP stones at 0.2 J/100 Hz, accompanied by strong spark-generation, explosive combustion, and diminished pressure transients, but not at 0.8 J/12 Hz. By treating stones in parallel fiber orientation and leveraging the proximity effect of a ureteroscope, the contribution of bubble collapse to stone ablation was found to be substantial (16% ~ 59%) at 0.8 J/12 Hz, but not at 0.2 J/100 Hz. Overall, TFL ablation efficiency is significantly better at high Ep/low F setting, attributable to increased cavitation damage with less char formation.

Insights gained from single-cell analysis of chimeric antigen receptor T-cell immunotherapy in cancer.

Advances in chimeric antigen receptor (CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies. However, progress is still hindered as clinical benefit is only available for a fraction of patients. A lack of understanding of CAR-T cell behaviors in vivo at the single-cell level impedes their more extensive application in clinical practice. Mounting evidence suggests that single-cell sequencing techniques can help perfect the receptor design, guide gene-based T cell modification, and optimize the CAR-T manufacturing conditions, and all of them are essential for long-term immunosurveillance and more favorable clinical outcomes. The information generated by employing these methods also potentially informs our understanding of the numerous complex factors that dictate therapeutic efficacy and toxicities. In this review, we discuss the reasons why CAR-T immunotherapy fails in clinical practice and what this field has learned since the milestone of single-cell sequencing technologies. We further outline recent advances in the application of single-cell analyses in CAR-T immunotherapy. Specifically, we provide an overview of single-cell studies focusing on target antigens, CAR-transgene integration, and preclinical research and clinical applications, and then discuss how it will affect the future of CAR-T cell therapy.

The use of histotripsy as intratumoral immunotherapy beyond tissue ablation-the rationale for exploring the immune effects of histotripsy.

Mechanical high-intensity focused ultrasound (M-HIFU), which includes histotripsy, is a non-ionizing, non-thermal ablation technology that can be delivered by noninvasive methods. Because acoustic cavitation is the primary mechanism of tissue disruption, histotripsy is distinct from the conventional HIFU techniques resulting in hyperthermia and thermal injury. Phase I human trials have shown the initial safety and efficacy of histotripsy in treating patients with malignant liver tumors. In addition to tissue ablation, a promising benefit of M-HIFU has been stimulating a local and systemic antitumor immune response in preclinical models and potentially in the Phase I trial. Preclinical studies combining systemic immune therapies appear promising, but clinical studies of combinations have been complicated by systemic toxicities. Consequently, combining M-HIFU with systemic immunotherapy has been demonstrated in preclinical models and may be testing in future clinical studies. An additional alternative is to combine intratumoral M-HIFU and immunotherapy using microcatheter-placed devices to deliver both M-HIFU and immunotherapy intratumorally. The promise of M-HIFU as a component of anti-cancer therapy is promising, but as forms of HIFU are tested in preclinical and clinical studies, investigators should report not only the parameters of the energy delivered but also details of the preclinical models to enable analysis of the immune responses. Ultimately, as clinical trials continue, clinical responses and immune analysis of patients undergoing M-HIFU including forms of histotripsy will provide opportunities to optimize clinical responses and to optimize application and scheduling of M-HIFU in the context of the multi-modality care of the cancer patient.

Dissimilar cavitation dynamics and damage patterns produced by parallel fiber alignment to the stone surface in holmium:yttrium aluminum garnet laser lithotripsy.

Recent studies indicate that cavitation may play a vital role in laser lithotripsy. However, the underlying bubble dynamics and associated damage mechanisms are largely unknown. In this study, we use ultra-high-speed shadowgraph imaging, hydrophone measurements, three-dimensional passive cavitation mapping (3D-PCM), and phantom test to investigate the transient dynamics of vapor bubbles induced by a holmium:yttrium aluminum garnet laser and their correlation with solid damage. We vary the standoff distance (SD) between the fiber tip and solid boundary under parallel fiber alignment and observe several distinctive features in bubble dynamics. First, long pulsed laser irradiation and solid boundary interaction create an elongated "pear-shaped" bubble that collapses asymmetrically and forms multiple jets in sequence. Second, unlike nanosecond laser-induced cavitation bubbles, jet impact on solid boundary generates negligible pressure transients and causes no direct damage. A non-circular toroidal bubble forms, particularly following the primary and secondary bubble collapses at SD = 1.0 and 3.0 mm, respectively. We observe three intensified bubble collapses with strong shock wave emissions: the intensified bubble collapse by shock wave, the ensuing reflected shock wave from the solid boundary, and self-intensified collapse of an inverted "triangle-shaped" or "horseshoe-shaped" bubble. Third, high-speed shadowgraph imaging and 3D-PCM confirm that the shock origins from the distinctive bubble collapse form either two discrete spots or a "smiling-face" shape. The spatial collapse pattern is consistent with the similar BegoStone surface damage, suggesting that the shockwave emissions during the intensified asymmetric collapse of the pear-shaped bubble are decisive for the solid damage.

High-Throughput Peptide Arrays Identify Potential Diagnostic Autoantibody Signatures in Early-Stage Lung Adenocarcinoma.

BACKGROUND: Early diagnosis is critical to lung adenocarcinoma patients' survival but faces inadequacies in convenient early detection. METHODS: We applied a comprehensive microarray of 130,000 peptides to detect "autoantibody signature" that is autoantibodies binding to mimotopes for early detection of stage 0-I LUAD. Plasma samples were collected from 147 early-stage lung adenocarcinoma (Early-LUAD), 108 benign lung disease (BLD), and 122 normal healthy controls (NHC). Clinical characteristics, low-dose CT (LDCT), and laboratory tests were incorporated into correlation analysis. RESULTS: We identified 143 and 133 autoantibody signatures, distinguishing Early-LUAD from NHC/BLD in the discovery cohort. Autoantibody signatures significantly correlated with age, stage, tumor size, basophil count, and IgM level (P < 0.05). The random forest models based on differential autoantibody signatures displayed AUC of 0.92 and 0.87 to discern Early-LUAD from NHC/BLD in the validation cohort, respectively. Compared with LDCT, combining autoantibody signature and LDCT improved the positive predictive value from 50% to 78.33% (P = 0.049). In addition, autoantibody signatures displayed higher sensitivity of 72.4% to 81.0% compared with the combinational tumor markers (cyfra21.1, NSE, SCC, ProGRP) with a sensitivity of 22.4% (P = 0.000). Proteins matched by differential peptides were enriched in cancer-related PI3K/Akt, MAPK, and Wnt pathways. Overlaps between matched epitopes and autoantibody signatures illustrated the underlying engagement of autoantibodies in immune recognition. CONCLUSIONS: Collectively, autoantibody signatures identified by a high-throughput peptide microarray have the potential to detect Early-LUAD, which could assist LDCT to better diagnose Early-LUAD. IMPACT: Novel sensitive autoantibody signatures can adjuvant LDCT to better diagnose LUAD at very early stage.

Increased risk of olfactory and taste dysfunction in the United States psoriasis population.

BACKGROUND: It is plausible that immunopathological processes associated with psoriasis might contribute to the occurrence of olfactory or taste dysfunction. However, the actual association was still unknown. PURPOSE: To determine the relationship between olfactory or taste dysfunction and psoriasis. METHODS: Two cross-sectional studies were performed by using National Health and Nutrition Examination Survey (NHANES) data. Participants with psoriasis were defined as cases and those without psoriasis were identified as controls. Taste and smell self-reported questionnaires were used to define smell/taste alterations and identification tests were used to assure the smell/taste dysfunctions. Logistic regression models with inverse probability treatment weighting (IPTW) strategies were conducted to investigated the relationship between psoriasis and olfactory or taste dysfunction. RESULTS: Self-reported questionnaires indicated that psoriasis patients were more likely to have perceived taste alteration (IPTW-aOR = 1.43) and smell alteration (IPTW-aOR = 1.22). Identification tests revealed that psoriasis was associated with taste dysfunction (IPTW-aOR = 1.28) and olfactory dysfunction (IPTW-aOR = 1.22). Relevant findings showed that psoriasis may be significantly associated with taste or olfactory dysfunction regardless of the questionnaire data or identification examination data used. CONCLUSION: Olfactory and taste dysfunction could be considered comorbidities in patients with psoriasis based on our observational study. Therefore, physicians should be cautious of olfaction and taste alterations among patients with psoriasis.

Combined Non-Invasive Prediction and New Biomarkers of Oral and Fecal Microbiota in Patients With Gastric and Colorectal Cancer.

Background: There is no information on the commonality and specificity of oral and fecal microbiota in patients with gastric cancer (GC) and colorectal cancer (CRC). Methods: The high-throughput 16S rRNA gene V4 region sequencing was used to perform bioinformatics analysis of oral, fecal, and tissue microbiota in GC (76 subjects), CRC (53), and healthy controls (HC, 70). Furthermore, we determined the microbial characteristics of each part, constructed and verified three classifiers for GC and CRC, and evaluated curves of receiver operating characteristic and precision-recall with probability of disease. Results: Compared to HC, the microbial richness and diversity of GC and CRC decreased in oral cavity and increased in stool; additionally, these indexes in GC tissue were higher than those in CRC tissue. In GC and CRC patients, Haemophilus, Neisseria, Faecalibacterium, and Romboutsia were significantly reduced compared to the relative abundance value of oral or fecal bacterial genera in the HC group, while the Streptococcus, Gemella, Escherichia-Shigella, and Fusobacterium were significantly increased. The oral and tissue microbiota have similar and abundant shared bacterial networks. The single and combined microbial detection have good AUC values based on POD indices for predicting GC, CRC, and gastrointestinal (GI) cancers (GC and CRC). Conclusion: This study is the first to examine the characteristics of oral, fecal, and tumor microbiota in GC and CRC patients, and the similarities and differences in their microbial changes are reported. These oral or fecal bacteria (Haemophilus, Neisseria, Faecalibacterium, Romboutsia, Streptococcus, Gemella, Escherichia-Shigella, and Fusobacterium) may be involved in tumor evolution as potentially characteristic genera. In addition, both oral and fecal microbial detection may provide a solid theoretical foundation for the non-invasive prediction of these cancers.

Combination of ultrasound-based mechanical disruption of tumor with immune checkpoint blockade modifies tumor microenvironment and augments systemic antitumor immunity.

BACKGROUND: Despite multimodal adjuvant management with radiotherapy, chemotherapy and hormonal therapies, most surgically resected primary breast cancers relapse or metastasize. A potential solution to late and distant recurrence is to augment systemic antitumor immunity, in part by appropriately presenting tumor antigens, but also by modulating the immunosuppressive tumor microenvironment (TME). We previously validated this concept in models of murine carcinoma treated with a novel predominately microcavitating version of high-intensity focused ultrasound (HIFU), mechanical high-intensity focused ultrasound (M-HIFU). Here we elucidated the mechanisms of enhanced antitumor immunity by M-HIFU over conventional thermal high-intensity focused ultrasound (T-HIFU) and investigated the potential of the combinatorial strategy with an immune checkpoint inhibitor, anti-PD-L1 antibody. METHODS: The antitumor efficacy of treatments was investigated in syngeneic murine breast cancer models using triple-negative (E0771) or human ErbB-2 (HER2) expressing (MM3MG-HER2) tumors in C57BL/6 or BALB/c mice, respectively. Induction of systemic antitumor immunity by the treatments was tested using bilateral tumor implantation models. Flow cytometry, immunohistochemistry, and single-cell RNA sequencing were performed to elucidate detailed effects of HIFU treatments or combination treatment on TME, including the activation status of CD8 T cells and polarization of tumor-associated macrophages (TAMs). RESULTS: More potent systemic antitumor immunity and tumor growth suppression were induced by M-HIFU compared with T-HIFU. Molecular characterization of the TME after M-HIFU by single-cell RNA sequencing demonstrated repolarization of TAM to the immunostimulatory M1 subtype compared with TME post-T-HIFU. Concurrent anti-PD-L1 antibody administration or depletion of CD4+ T cells containing a population of regulatory T cells markedly increased T cell-mediated antitumor immunity and tumor growth suppression at distant, untreated tumor sites in M-HIFU treated mice compared with M-HIFU monotherapy. CD8 T and natural killer cells played major roles as effector cells in the combination treatment. CONCLUSIONS: Physical disruption of the TME by M-HIFU repolarizes TAM, enhances T-cell infiltration, and, when combined with anti-PD-L1 antibody, mediates superior systemic antitumor immune responses and distant tumor growth suppression. These findings suggest M-HIFU combined with anti-PD-L1 may be useful in reducing late recurrence or metastasis when applied to primary tumors.

Comparison of Different Pulse Modulation Modes for Holmium:Yttrium-Aluminum-Garnet Laser Lithotripsy Ablation in a Benchtop Model.

Introduction: Manipulation of Holmium:Yttrium-Aluminum-Garnet laser parameters such as pulse energy (PE), frequency, and duration can impact laser lithotripsy ablation efficiency. In 2017, Lumenis introduced Moses™ Technology, which uses pulse modulation to enhance the delivery of energy from fiber to stone as well as to minimize stone retropulsion. Since the introduction of Moses Technology, other companies have brought additional pulse modulation concepts to market. The purpose of this in vitro study is to compare the pulse characteristics and stone ablation efficiency of Lumenis Moses Technology with Quanta's Vapor Tunnel™. Materials and Methods: Submerged BegoStone phantoms were systematically ablated using either the Lumenis Moses Pulse 120H or the Quanta Litho 100 clinical laser system. Two PEs (0.4 and 1 J), three fiber-stone standoff distances (SDs) (0.5, 1, 2 mm), and all available pulse duration and modulation modes for each laser were tested in combination. Fiber speed was adjusted to scan across the stone surface at either 1 or 10 pulses/mm to form single pulse craters or an ablation trough, respectively. Volumes of single craters and 1 mm trough segments were imaged and quantified using optical coherence tomography. Results: Ablation volumes decreased with decreasing PE and increasing SD. Statistically significant variability was seen between pulse types (PT) at every tested parameter set. Among pulse modulation modes, Moses Distance (MD) was superior at 0.5 mm in all testing and at 2 mm in trough testing. Vapor Tunnel (VT) was superior in 2 mm single crater testing. All modulated pulses performed similarly at 1 mm. Conclusions: In this benchtop model of laser lithotripsy, stone ablation was significantly impacted by PT. MD demonstrated superior or noninferior stone ablation at most tested parameters. VT maintained its efficacy the best as SD increased. Future work should focus on the mechanistic differences of these modes relative to other traditional laser pulse modes.

Photoacoustic computed tomography of mechanical HIFU-induced vascular injury.

Mechanical high-intensity focused ultrasound (HIFU) has been used for cancer treatment and drug delivery. Existing monitoring methods for mechanical HIFU therapies such as MRI and ultrasound imaging often suffer from high cost, poor spatial-temporal resolution, and/or low sensitivity to tissue's hemodynamic changes. Evaluating vascular injury during mechanical HIFU treatment, therefore, remains challenging. Photoacoustic computed tomography (PACT) is a promising tool to meet this need. Intrinsically sensitive to optical absorption, PACT provides high-resolution imaging of blood vessels using hemoglobin as the endogenous contrast. In this study, we have developed an integrated HIFU-PACT system for detecting vascular rupture in mechanical HIFU treatment. We have demonstrated singular value decomposition for enhancing hemorrhage detection. We have validated the HIFU-PACT performance on phantoms and in vivo animal tumor models. We expect that PACT-HIFU will find practical applications in oncology research using small animal models.

Mechanically induced integrin ligation mediates intracellular calcium signaling with single pulsating cavitation bubbles.

Therapeutic ultrasound or shockwave has shown its great potential to stimulate neural and muscle tissue, where cavitation microbubble induced Ca2+ signaling is believed to play an important role. However, the pertinent mechanisms are unknown, especially at the single-cell level. Particularly, it is still a major challenge to get a comprehensive understanding of the effect of potential mechanosensitive molecular players on the cellular responses, including mechanosensitive ion channels, purinergic signaling and integrin ligation by extracellular matrix. Methods: Here, laser-induced cavitation microbubble was used to stimulate individual HEK293T cells either genetically knocked out or expressing Piezo1 ion channels with different normalized bubble-cell distance. Ca2+ signaling and potential membrane poration were evaluated with a real-time fluorescence imaging system. Integrin-binding microbeads were attached to the apical surface of the cells at mild cavitation conditions, where the effect of Piezo1, P2X receptors and integrin ligation on single cell intracellular Ca2+ signaling was assessed. Results: Ca2+ responses were rare at normalized cell-bubble distances that avoided membrane poration, even with overexpression of Piezo1, but could be increased in frequency to 42% of cells by attaching integrin-binding beads. We identified key molecular players in the bead-enhanced Ca2+ response: increased integrin ligation by substrate ECM triggered ATP release and activation of P2X-but not Piezo1-ion channels. The resultant Ca2+ influx caused dynamic changes in cell spread area. Conclusion: This approach to safely eliciting a Ca2+ response with cavitation microbubbles and the uncovered mechanism by which increased integrin-ligation mediates ATP release and Ca2+ signaling will inform new strategies to stimulate tissues with ultrasound and shockwaves.

Time-Resolved Passive Cavitation Mapping Using the Transient Angular Spectrum Approach.

Passive cavitation mapping (PCM), which generates images using bubble acoustic emission signals, has been increasingly used for monitoring and guiding focused ultrasound surgery (FUS). PCM can be used as an adjunct to magnetic resonance imaging to provide crucial information on the safety and efficacy of FUS. The most widely used algorithm for PCM is delay-and-sum (DAS). One of the major limitations of DAS is its suboptimal computational efficiency. Although frequency-domain DAS can partially resolve this issue, such an algorithm is not suitable for imaging the evolution of bubble activity in real time and for cases in which cavitation events occur asynchronously. This study investigates a transient angular spectrum (AS) approach for PCM. The working principle of this approach is to backpropagate the received signal to the domain of interest and reconstruct the spatial-temporal wavefield encoded with the bubble location and collapse time. The transient AS approach is validated using an in silico model and water bath experiments. It is found that the transient AS approach yields similar results to DAS, but it is one order of magnitude faster. The results obtained by this study suggest that the transient AS approach is promising for fast and accurate PCM.

[Professor LIN Guo-hua's experience in the new clinical application of Yinjiao (GV 28)].

Yinjiao (GV 28) is generally used in treatment of lumbago and anorectal diseases. Professor LIN Guo-hua believes that Yinjiao (GV 28) is indicated in the disorders related to the sea of marrow and lower jiao by regulating the governor vessel and the conception vessel, promoting qi and blood circulation, tonifying the sea of marrow and adjusting the lower jiao. Based on professor Lin's clinical experience, "three Yinjiao" points are innovated, named Yinjiao (GV 28, upper Yinjiao), external Yinjiao and lower Yinjiao. Acupuncture therapy is generally optioned at Yinjiao (GV 28) and 5 needling principles are emphasized, i.e. accurate acupoint location, strong needling sensation, needling combined with body movement, alternative stimulation and allied stimulation. All of those mentioned above provide a new approach to the clinical treatment for the disorders related to the sea of marrow and lower jiao.

Miniaturized Intracavitary Forward-Looking Ultrasound Transducer for Tissue Ablation.

OBJECTIVE: This paper aims to develop a miniaturized forward-looking ultrasound transducer for intracavitary tissue ablation, which can be used through an endoscopic device. The internal ultrasound (US) delivery is capable of directly interacting with the target tumor, resolving adverse issues of currently available US devices, such as unintended tissue damage and insufficient delivery of acoustic power. METHODS: To transmit a high acoustic pressure from a small aperture (<3 mm), a double layer transducer (1.3 MHz) was designed and fabricated based on numerical simulations. The electric impedance and the acoustic pressure of the actual device was characterized with an impedance analyzer and a hydrophone. Ex vivo tissue ablation tests and temperature monitoring were then conducted with porcine livers. RESULTS: The acoustic intensity of the transducer was 37.1 W/cm2 under 250 Vpp and 20% duty cycle. The tissue temperature was elevated to 51.8 °C with a 67 Hz pulse-repetition frequency. The temperature profile in the tissue indicated that ultrasound energy was effectively absorbed inside the tissue. During a 5-min sonification, an approximate tissue volume of 2.5 × 2.5 × 1.0 mm3 was ablated, resulting in an irreversible lesion. CONCLUSION: This miniaturized US transducer is a promising medical option for the precise tissue ablation, which can reduce the risk of unintended tissue damage found in noninvasive US treatments. SIGNIFICANCE: Having a small aperture (2 mm), the intracavitary device is capable of ablating a bio tissue in 5 min with a relatively low electric power (<17 W).

Activation of Piezo1 mechanosensitive ion channel in HEK293T cells by 30 MHz vertically deployed surface acoustic waves.

Ultrasound (US) has emerged as a promising noninvasive modality for neuromodulation. Despite previous evidence that US may mediate cellular response by activating mechanosensitive ion channels embedded in the cell membrane, the underlying mechanism is not well understood. In this work, we developed a vertically deployed surface acoustic wave (VD-SAW) platform that generates 30 MHz focused ultrasound wave for mechanical stimulation of single cells. We investigated the role of Piezo1 in mediating the intracellular calcium response ( [Formula: see text] ) of HEK293T cells in response to pulsed US operated at a peak pressure of 1.6 MPa with 20% duty cycle, and a total treatment time of 60 s. We observed that the elicited calcium response depends critically on the pulse repetition frequency (PRF) or burst duration of the US, as well as the presence of the Piezo1. Significantly higher [Formula: see text] increase was produced in the Piezo1-transfected (P1TF) than in the Piezo1-knockout (P1KO) HEK293T cells. Furthermore, higher calcium response probability, stronger and faster [Formula: see text] increase, and greater cell displacement were produced at 2 Hz PRF with 100 ms burst duration than 200 Hz PRF with 1 ms burst duration. Altogether, we have demonstrated that the VD-SAW platform provides a unique and versatile tool for investigating US-induced mechanotransduction at the single cell level.

Thermal Memory Based Photoacoustic Imaging of Temperature.

Temperature mapping is essential in many biomedical studies and interventions to precisely control the tissue's thermal conditions for optimal treatment efficiency and minimal side effects. Based on the Grüneisen parameter's temperature dependence, photoacoustic (PA) imaging can provide relative temperature measurement, but it has been traditionally challenging to measure absolute temperatures without knowing the baseline temperature, especially in deep tissues with unknown optical and acoustic properties. Here, we report a new thermal-energy-memory-based photoacoustic thermometry (TEMPT). By illuminating the tissue with a burst of nanosecond laser pulses, TEMPT exploits the temperature dependence of the thermal energy lingering, which is probed by the corresponding PA signals acquired within the thermal confinement. A self-normalized ratiometric measurement cancels out temperature-irrelevant quantities and estimates the Grüneisen parameter. The temperature can then be evaluated, given the tissue's temperature-dependent Grüneisen parameter, mass density, and specific heat capacity. Unlike the conventional PA thermometry, TEMPT does not require the knowledge of tissue's baseline temperature, nor the optical properties. We have developed a mathematical model to describe the temperature dependence in TEMPT. We have demonstrated the feasibility of the temperature evaluation on tissue phantoms at 1.5 cm depth within a clinically relevant temperature range. Finally, as proof-of-concept, we applied TEMPT for temperature mapping during focused ultrasound treatment in mice in vivo at 2 mm depth. As a generic temperature mapping method, TEMPT is expected to find applications in thermotherapy of cancers on small animal models.

Analysis of age-related changes in midfacial fat compartments in Asian women using computed tomography.

BACKGROUND: Volume restoration is no more a fresh theory for midfacial rejuvenation. However, lack of knowledge regarding the natural ageing process of fat compartments often leads to an insufficient or excessive clinical result. The aim of this study is to reveal the age-related changes in midfacial fat compartments and the correlation between midfacial grooves and the related fat compartments. METHODS: This study included 60 Asian females in defined age-based categories. The thickness of the infraorbital fat compartment, the nasolabial fat compartment, and the cheek fat compartments were measured using computed tomography (CT) images. Analysis of correlations between midfacial grooves and the related fat compartments was performed using the SPSS software. RESULTS: A tendency of thickening in the infraorbital fat and nasolabial fat compartments with age was observed. The superficial layer of cheek fat compartments was found to be thinner, and a similar tendency was observed in the medial part of deep medial cheek fat. However, it was thicker in the lateral part of deep medial cheek fat. There was a negative correlation between the fat thickness of deep medial cheek fat and both the severity of tear trough deformity and the nasolabial fold. A positive correlation between the lower third of the nasolabial fat compartment and the severity of the nasolabial fold was found as well. CONCLUSION: Different midfacial fat compartments tended to undergo selective hypertrophy or atrophy with ageing. The findings of this study suggested that augmentation of the deflated fat compartment and liposuction of the hypertrophic fat compartment can provide a more natural effect in facial rejuvenation.