Exploring the association between multiple factors and urolithiasis: A retrospective study and Mendelian randomization analysis.

To investigate the relationship between several factors and urinary stone as well as different stone compositions. To guide the diagnosis, treatment, and prevention of urinary stone recurrence. We used bidirectional Mendelian randomization to analyze the causal relationship between hypertension and urinary stones, diabetes and urinary stones, and body mass index (BMI) and urinary stones. We retrospectively analyzed the medical records of patients with urinary stones admitted to a tertiary care hospital in Chongqing, China, from July 2015 to October 2022. Patients were included when they were first diagnosed with urinary stones. The odds ratio of calculi on hypertension estimated by inverse variance weighted was 8.46 (95%CI: 4.00-17.90, P = 2.25 × 10-8). The stone composition analysis showed that there were 3101 (67.02%) mixed, 1322 (28.57%) calcium oxalate monohydrate, 148 (3.20%) anhydrous uric acid, 16 (0.35%) magnesium ammonium phosphate hexahydrate, 11 (0.24%) dicalcium phosphate dihydrate, 10 (0.22%) carbonate apatite, 8 (0.17%) L-cystine, 4 ammonium uric acid (0.09%), and 7 other stone types (0.15%). Mendelian randomization studies have proven that urinary stones may be a potential risk factor for hypertension, while there is no causal relationship between diabetes and stones, BMI, and stones. Our retrospective study has shown that urinary stone components are closely associated with sex, age, hypertension, diabetes, and BMI. It is reasonable to suspect that treating a single stone component is ineffective in preventing recurrence. We also found that the peak incidence of urinary stones was at the most active stage of most people's working lives.

Attenuated polyethylene glycol immunogenicity and overcoming accelerated blood clearance of a fully PEGylated dendrimer.

Polyethylene glycol (PEG) is a popular biocompatible polymer and PEGylated nanoparticles passively accumulate in tumor tissues because of their enhanced permeability and retention effects. Recently, the anti-PEG immunity of PEGylated nanoparticles has become an issue that needs to be solved for their clinical applications. Dendrimers are highly branched and well-defined polymers with many terminal groups, which act as potent drug carriers. In this study, we examined the pharmacokinetics, biodistribution, anti-PEG immunity, and tumor accumulation of a fully PEGylated polyamidoamine (PAMAM) dendrimer after the first and second injections and compared them to those of a PEGylated liposome with the same lipid component as Doxil®. The PEGylated dendrimer showed greater blood circulation than that of the PEGylated liposome after the first and second injections in rats. In mice injected with the PEGylated dendrimer, much less anti-PEG immunoglobulin M (IgM) was generated than that in mice injected with the PEGylated liposome. The PEGylated dendrimer accumulated in the tumor after both the first and second injections. Our results indicated that the PEGylated dendrimer with a small size and high PEG density showed attenuated anti-PEG immunity and overcame the accelerated blood clearance phenomenon, which is useful for drug delivery systems for cancer treatment.

Two novel ketone alkaloids from Portulaca oleraceaL. and their anti-inflammatory activities.

Eleven compounds were obtained from Portulaca oleracea L., including two novel ketone alkaloids, (1, 2), 4-hydroxy-3-methoxybenzamide (3) (isolated for the first time), ß-adenosine (4), oleracrylimide A and B (5, 6), oleracein H, C, D, Q and A (7-11). The two novel ketone alkaloids were identified as 5-acetyl-5-methylcyclopent-2-ene-1-carboxamide (1), named oleraciamide H, and (2 R,3S,4R,5R)-5-((R)-1,2-dihydroxyethyl)-3,4-dihydroxytetrahydrofuran-2-yl glycinate (2), named oleracone Q by spectroscopic methods, including 1D, 2D NMR and compound fingerprints. Additionally, their anti-inflammatory activities were tested via RAW 264.7 cells induced by LPS and found that they could significantly inhibit the release of IL-1ß and TNF-α.

Potential Effect of Acupuncture on Mitochondrial Biogenesis, Energy Metabolism and Oxidation stress in MCAO Rat via PGC-1α/NRF1/TFAM pathway.

PURPOSE: To explore possible mechanism(s) underlying beneficial effects of acupuncture treatment for alleviating focal cerebral infarction-induced neuronal injury, mitochondrial biogenesis, energy metabolism, oxidative stress and dendrite regeneration were evaluated in rats with experimentally induced cerebral ischemia and dendron reperfusion. MATERIALS AND METHODS: Rats were randomly assigned to three groups (sham-operated, operated group without acupuncture, operated group with acupuncture). RT-PCR and Western blotting were used to assess variations of hippocampal cell mitochondrial DNA (mtDNA) copy number and mRNA and protein expression levels associated with key mitochondrial biogenesis proteins, namely peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiration factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). To evaluate mitochondrial oxidative phosphorylation and respiratory function in ischemic tissues, oxidative phosphorylation protein complex expression levels were assessed via Western blot analysis, mitochondrial membrane potential (MMP) was assessed via confocal microscopy and flow cytometry and adenosine triphosphate (ATP) concentration was assessed using an enzymatic fluorescence-based assay. Immunofluorescence staining was used to evaluate the expression of the neuronal dendron formation marker-Microtubule Associated Protein 2 (MAP2). Additionally, oxidative stress levels were assessed based on superoxide dismutase (SOD) activity, lipid oxidation levels (malondialdehyde, MDA) and glutathione (GSH) levels. Meanwhile, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl staining, transmission electron microscopy observation and neuro behavioral status were used to determine cerebral infarction volume and extent of brain injury. RESULTS: Acupuncture treatment effectively stimulated mRNA-level and protein-level expression associated with PGC-1α, NRF-1 and TFAM and increased levels of electron transport chain complexes I, IV and V, thereby increasing the ATP concentration, maintaining mitochondrial membrane potential, and promoting dendron regeneration levels. Meanwhile, in hippocampal neurons SOD activity and the glutathione/glutathione disulfide (GSH/GSSG) ratio increased and MDA level decreased. CONCLUSION: Acupuncture treatment after ischemic injury promoted mitochondrial biogenesis, as reflected by beneficially increased mitochondrial oxidative phosphorylation complex protein levels and brain tissue energy supply, while preventing oxidative stress injury. These results should guide future explorations to elucidate acupuncture-based mechanisms for alleviating neuronal injury triggered by acute cerebral ischemia.

Association between different composite dietary antioxidant indexes and low back pain in American women adults: a cross-sectional study from NHANES.

BACKGROUND: Low back pain is the leading cause of productivity loss, imposes a significant economic burden on the patients and society. Oxidative stress is considered a critical factor in the complex pathophysiological process and pathogenic mechanism of low back pain. Adjustment dietary pattern can effectively increase antioxidant biomarkers levels within the body to reduce oxidative stress. The composite dietary antioxidant index (CDAI) serves a reliable scoring system for quantifying the potential dietary antioxidant capacity of daily diets. OBJECTIVE: We aim to investigate the potential association between CDAI and low back pain, in order to enhance the management of low back pain through dietary guidance. METHODS: This study included 17,682 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2000, 2001-2002, 2003-2004 and 2009-2010. The weighted logistic regression model was used to investigate the association between CDAI and low back pain, while restricted cubic spline (RCS) was employed to examine non-linear trend and cutoffs. RESULTS: After adjusting for all confounders, the results showed that there was no significant association between CDAI and low back pain. However, individuals in the highest quartile of CDAI exhibited an 11.7% less likelihood of experiencing a low back pain than those in the lowest quartile (OR = 0.883; 95% CI [0.787,0.991], P = 0.034), and the trend test was also significant (P for trend < 0.001). RCS indicated a linear relationship between CDAI and low back pain (P for non-linear = 0.876). Gender subgroup analysis showed that this negative association was significant in the female population (OR = 0.983; 95% CI [0.968, 0.998], P = 0.027), and females in the highest quartile of CDAI were 19.7% less likely to suffer low back pain than those in the lowest quartile (OR = 0.803; 95% CI [0.682,0.945], P = 0.008). Additionally, the changes in zinc (OR = 1.009; 95% CI [1.002, 1.016], P = 0.015) and selenium (OR = 0.379; 95% CI [0.164, 0.875], P = 0.023) per milligram were independently associated with low back pain. CONCLUSION: The fully adjusted model showed no significant association between CDAI and low back pain, but it was significant in quartiles. Meanwhile, subgroup analysis by gender revealed a negative association between CDAI and low back pain in the female population. Additionally, the findings of this study also suggested that the antioxidant diets should be studied in a dietary pattern context.

Comparison of a novel tablet formulation of tacrolimus and conventional capsule formulation in de novo kidney transplant recipients: a systematic review and meta-analysis.

Background: The work aimed to compare the pharmacokinetic (PK) profiles and other outcomes reported in observational studies in de novo kidney transplant recipients (KTRs) receiving novel once-daily extended-release tablet tacrolimus (LCPT; LCP-tacrolimus; Envarsus XR) or receiving standard-of-care capsule tacrolimus (PR-Tac; prolonged-release tacrolimus; Advagraf/IR-Tac; immediate-release tacrolimus; Prograf). Methods: A systematic review was conducted for all randomized controlled trials (RCTs) and cohort studies investigating the outcomes in KTRs receiving LCPT or PR-Tac/IR-Tac. We systematically searched PubMed, Web of Science, and EMBASE, with no language restriction. The registered trials and references listed in relevant studies were also searched. Data were extracted for the PK profile, tacrolimus trough level (TTL), and changes in the estimated glomerular filtration rate (eGFR) and serum creatinine (Scr), biopsy-proven acute rejection (BPAR) rate, delayed graft function (DGF) rate, post-transplant diabetes mellitus (PTDM) rate, tremor rate (TR), death rate (DR), and rate of infection by cytomegalovirus (CMV). This study was registered with PROSPERO (registration number: CRD42023403787). Results: A total of seven eligible articles including 1,428 patients with 712 in the LCPT group versus 716 in the PR-Tac/IR-Tac group were included in this study for evidence synthesis. The baseline characteristics of the LCPT, PR-Tac, and IR-Tac groups were similar. The pooled analysis showed a higher PK profile in the LCPT group, and this result was consistent with those of all the included studies. In addition, no significant difference was observed for other outcomes. Conclusion: Considering heterogeneity between studies and potential bias, care providers should select agents based on patient-specific factors and their clinical experience for the immunosuppressive treatment of de novo KTRs.

A new alkaloid from Portulaca oleracea L. with its anti-inflammatory activity.

A new isoindole alkaloid, 6-hydroxy-2-(4'''-hydroxy-3'''-methoxyphenethyl)-4-(4'-hydroxy-3'-methoxyphenyl)-7-methoxy-1H-benzo[f]isoindole-1,3(2H)-dione, named oleraisoindole B was isolated from Portulaca oleracea L., its structure was elucidated using NMR and UHPLC-ESI-Q-TOF/MS spectroscopic methods, and presented anti-inflammatory activity at 5 µM.

The sound of blood: photoacoustic imaging in blood analysis.

Blood analysis is a ubiquitous and critical aspect of modern medicine. Analyzing blood samples requires invasive techniques, various testing systems, and samples are limited to relatively small volumes. Photoacoustic imaging (PAI) is a novel imaging modality that utilizes non-ionizing energy that shows promise as an alternative to current methods. This paper seeks to review current applications of PAI in blood analysis for clinical use. Furthermore, we discuss obstacles to implementation and future directions to overcome these challenges. Firstly, we discuss three applications to cellular analysis of blood: sickle cell, bacteria, and circulating tumor cell detection. We then discuss applications to the analysis of blood plasma, including glucose detection and anticoagulation quantification. As such, we hope this article will serve as inspiration for PAI's potential application in blood analysis and prompt further studies to ultimately implement PAI into clinical practice.

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.

Plasmonic nanorod probes' journey inside plant cells for in vivo SERS sensing and multimodal imaging.

Nanoparticle-based platforms are gaining strong interest in plant biology and bioenergy research to monitor and control biological processes in whole plants. However, in vivo monitoring of biomolecules using nanoparticles inside plant cells remains challenging due to the impenetrability of the plant cell wall to nanoparticles beyond the exclusion limits (5-20 nm). To overcome this physical barrier, we have designed unique bimetallic silver-coated gold nanorods (AuNR@Ag) capable of entering plant cells, while conserving key plasmonic properties in the near-infrared (NIR). To demonstrate cellular internalization and tracking of the nanorods inside plant tissue, we used a comprehensive multimodal imaging approach that included transmission electron microscopy (TEM), confocal fluorescence microscopy, two-photon luminescence (TPL), X-ray fluorescence microscopy (XRF), and photoacoustics imaging (PAI). We successfully acquired SERS signals of nanorods in vivo inside plant cells of tobacco leaves. On the same leaf samples, we applied orthogonal imaging methods, TPL and PAI techniques for in vivo imaging of the nanorods. This study first demonstrates the intracellular internalization of AuNR@Ag inside whole plant systems for in vivo SERS analysis in tobacco cells. This work demonstrates the potential of this nanoplatform as a new nanotool for intracellular in vivo biosensing for plant biology.

Multiscale photoacoustic tomography using reversibly switchable thermochromics.

Significance: Based on acoustic detection of optical absorption, photoacoustic tomography (PAT) allows functional and molecular imaging beyond the optical diffusion limit with high spatial resolution. However, multispectral functional and molecular PAT is often limited by decreased spectroscopic accuracy and reduced detection sensitivity in deep tissues, mainly due to wavelength-dependent optical attenuation and inaccurate acoustic inversion. Aim: Previous work has demonstrated that reversible color-shifting can drastically improve the detection sensitivity of PAT by suppressing nonswitching background signals. We aim to develop a new color switching-based PAT method using reversibly switchable thermochromics (ReST). Approach: We developed a family of ReST with excellent water dispersion, biostability, and temperature-controlled color changes by surface modification of commercial thermochromic microcapsules with the hydrophilic polysaccharide alginate. Results: The optical absorbance of the ReST was switched on and off repeatedly by modulating the surrounding temperature, allowing differential photoacoustic detection that effectively suppressed the nonswitching background signal and substantially improved image contrast and detection sensitivity. We demonstrate reversible thermal-switching imaging of ReST in vitro and in vivo using three PAT modes at different length scales. Conclusions: ReST-enabled PAT is a promising technology for high-sensitivity deep tissue imaging of molecular activity in temperature-related biomedical applications, such as cancer thermotherapy.

Acute hepatitis of unknown origin in children: A combination of factors.

On 5 April 2022, the World Health Organization was notified of 10 cases of severe acute hepatitis of unknown etiology in children under 10 years of age in the United Kingdom. Although the exact cause of a proportion of pediatric acute hepatitis and acute liver failure cases was unclear, the above event has caused widespread concern worldwide. As of 14 September 2022, approximately 1,296 probable cases of acute hepatitis of unknown etiology have been reported from 37 countries/regions, of which approximately 55 required or received liver transplantation and 29 died. Although the etiology of acute hepatitis of unknown origin in children remains unclear, many hypotheses have been proposed about the disease. Instead of individual factors such as "adenovirus infection," "SARS-CoV-2 related," and "Adeno-associated virus 2 with helper virus coinfection," it is more likely due to a combination of factors. Accordingly, there is an urgent need for more data and research to clarify the disease etiology. This review aims to provide a historical perspective of acute hepatitis of unknown etiology in children in the past decades and summarize the current hypothesis and evidence on this emerging disease.

Mechanisms of the Bushen Huoxue formula in the treatment of osteoarthritis based on network pharmacology-molecular targets.

BACKGROUND: Osteoarthritis is a common degenerative disease with a high incidence, high disability rate, and poor prognosis. Clinical studies have shown that Bushen Huoxue formula can relieve joint swelling and pain and improve limb function and joint mobility, but there is a lack of high-quality scientific basis. Using network pharmacology and molecular docking technology to study the mechanism of Bushen Huoxue formula in the treatment of osteoarthritis. METHODS: First, the active ingredients and corresponding target predictions of the formula were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the China National Knowledge Infrastructure. Meanwhile, the osteoarthritis disease targets were obtained through the genome annotation database platform (GeneCards) and the DrugBank database, and the target proteins obtained above were standardized using the Uniprot (https://www.uniprot.org) database standardization of names. Then, the Venn diagram was created by taking the intersection of the active ingredient and the target of the disease, and the "active ingredient-target" network was constructed and analyzed using Cytoscape 3.7.2 software. At the same time, the intersecting targets were imported into the Search Tool for the Retrieval of Interaction Gene/Proteins database to build a protein-protein interaction network and to screen the core targets; the intersecting targets were visualized by using the Database for Annotation, Visualization and Integrated Discovery 6.8 database for gene ontology functional analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and construct the "active ingredient-target-pathway" network. Finally, the main active ingredients of the formula for tonifying the kidney and invigorating the blood were validated by molecular docking with the core targets. RESULTS: A total of 194 active ingredients and 365 targets of the Bushen Huoxue formula were collected, 776 targets for osteoarthritis diseases and 96 targets for the intersection of active ingredients and diseases. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 104 relevant pathways, including tumor necrosis factor signaling pathways, cancer signaling pathways, nucleotide-binding oligomerization domain-like receptor signaling pathways, Toll-like receptors signaling pathways, and osteoclast differentiation, apoptosis, T-cell receptor signaling pathway, and other related pathways. The molecular docking results showed good binding of the main active ingredients to the core targets. CONCLUSION: This study shows that the treatment of osteoarthritis involves multicomponent, multitarget, and multipathway processes. The mechanism of anti-inflammatory, antioxidant, inhibition of cartilage matrix degradation, and reduction of subchondral bone destruction may be an important mechanism for the therapeutic effect.

Three-Dimensional Deep-Tissue Functional and Molecular Imaging by Integrated Photoacoustic, Ultrasound, and Angiographic Tomography (PAUSAT).

Non-invasive small-animal imaging technologies, such as optical imaging, magnetic resonance imaging and x -ray computed tomography, have enabled researchers to study normal biological phenomena or disease progression in their native conditions. However, existing small-animal imaging technologies often lack either the penetration capability for interrogating deep tissues (e.g., optical microscopy), or the functional and molecular sensitivity for tracking specific activities (e.g., magnetic resonance imaging). To achieve functional and molecular imaging in deep tissues, we have developed an integrated photoacoustic, ultrasound and acoustic angiographic tomography (PAUSAT) system by seamlessly combining light and ultrasound. PAUSAT can perform three imaging modes simultaneously with complementary contrast: high-frequency B-mode ultrasound imaging of tissue morphology, microbubble-enabled acoustic angiography of tissue vasculature, and multi-spectral photoacoustic imaging of molecular probes. PAUSAT can provide three-dimensional (3D) multi-contrast images that are co-registered, with high spatial resolutions at large depths. Using PAUSAT, we performed proof-of-concept in vivo experiments on various small animal models: monitoring longitudinal development of placenta and embryo during mouse pregnancy, tracking biodistribution and metabolism of near-infrared organic dye on the whole-body scale, and detecting breast tumor expressing genetically-encoded photoswitchable phytochromes. These results have collectively demonstrated that PAUSAT has broad applicability in biomedical research, providing comprehensive structural, functional, and molecular imaging of small animal models.

Seeing through the Skin: Photoacoustic Tomography of Skin Vasculature and Beyond.

Skin diseases are the most common human diseases and manifest in distinct structural and functional changes to skin tissue components such as basal cells, vasculature, and pigmentation. Although biopsy is the standard practice for skin disease diagnosis, it is not sufficient to provide in vivo status of the skin and highly depends on the timing of diagnosis. Noninvasive imaging technologies that can provide structural and functional tissue information in real time would be invaluable for skin disease diagnosis and treatment evaluation. Among the modern medical imaging technologies, photoacoustic (PA) tomography (PAT) shows great promise as an emerging optical imaging modality with high spatial resolution, high imaging speed, deep penetration depth, rich contrast, and inherent sensitivity to functional and molecular information. Over the last decade, PAT has undergone an explosion in technical development and biomedical applications. Particularly, PAT has attracted increasing attention in skin disease diagnosis, providing structural, functional, metabolic, molecular, and histological information. In this concise review, we introduce the principles and imaging capability of various PA skin imaging technologies. We highlight the representative applications in the past decade with a focus on imaging skin vasculature and melanoma. We also envision the critical technical developments necessary to further accelerate the translation of PAT technologies to fundamental skin research and clinical impacts.

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.

Selenoprotein S attenuates high glucose and/or ox-LDL-induced endothelium injury by regulating Akt/mTOR signaling and autophagy.

Glucolipid metabolism disorder in diabetes mellitus (DM) causes human endothelial injury and autophagy dysfunction is an important cause of endothelial dysfunction (ED). Selenoprotein S (SelS) could protect endothelium from oxidative stress, inflammatory responses, and apoptosis. This study assessed the effect of SelS on autophagy in glucolipid metabolic disorders and protection of the resulted vascular endothelial injury. The results showed that high glucose (HG), high oxidized low-density lipoprotein (HL), and HG combined with HL (HGL) could reduce viability of human aortic endothelial cells (HAECs), induce HAECs injury and increase SelS expression in a time-dependent manner. HG, HL, and HGL also initially induced autophagy but later reduced it in HAECs, while activity of the Akt/mTOR signaling was inhibited, especially in HGL culture of HAECs. SelS overexpression reduced the endothelial injury and autophagy and activated the Akt/mTOR signaling in HG, HL and HGL-cultured HAECs, compared to the control. Conversely, knockdown of SelS expression had the opposite effects on HAECs. In conclusion, SelS demonstrated a protective effect on endothelial injury induced by high glucose and/or ox-LDL and the underlying molecular events might be related to its regulation of HAECs autophagy by activating the Akt/mTOR signaling. SelS could be a potential intervention target in prevention and treatment of diabetic vascular complications.

Translational Photoacoustic Imaging for Disease Diagnosis, Monitoring, and Surgical Guidance: introduction to the feature issue.

This feature issue of Biomedical Optics Express covered all aspects of translational photoacoustic research. Application areas include screening and diagnosis of diseases, imaging of disease progression and therapeutic response, and image-guided treatment, such as surgery, drug delivery, and photothermal/photodynamic therapy. The feature issue also covers relevant developments in photoacoustic instrumentation, contrast agents, image processing and reconstruction algorithms.

Perspective on fast-evolving photoacoustic tomography.

SIGNIFICANCE: Acoustically detecting the rich optical absorption contrast in biological tissues, photoacoustic tomography (PAT) seamlessly bridges the functional and molecular sensitivity of optical excitation with the deep penetration and high scalability of ultrasound detection. As a result of continuous technological innovations and commercial development, PAT has been playing an increasingly important role in life sciences and patient care, including functional brain imaging, smart drug delivery, early cancer diagnosis, and interventional therapy guidance. AIM: Built on our 2016 tutorial article that focused on the principles and implementations of PAT, this perspective aims to provide an update on the exciting technical advances in PAT. APPROACH: This perspective focuses on the recent PAT innovations in volumetric deep-tissue imaging, high-speed wide-field microscopic imaging, high-sensitivity optical ultrasound detection, and machine-learning enhanced image reconstruction and data processing. Representative applications are introduced to demonstrate these enabling technical breakthroughs in biomedical research. CONCLUSIONS: We conclude the perspective by discussing the future development of PAT technologies.

Instant Ultrasound-Evoked Precise Nanobubble Explosion and Deep Photodynamic Therapy for Tumors Guided by Molecular Imaging.

Nanobubbles (NBs) have recently gained interest in cancer imaging and therapy due to the fact that nanoparticles with the size range of 1-1000 nm can extravasate into permeable tumor types through the enhanced permeability and retention (EPR) effect. However, the therapeutic study of NBs was only limited to drug delivery or cavitation. Herein, we developed ultrasound-evoked massive NB explosion to strikingly damage the surrounding cancer. The dual-function agent allows synergistic mechanical impact and photodynamic therapy of the tumors and enhances imaging contrast. Moreover, the mechanical explosion improved the light delivery efficiency in biological tissue to promote the effect of photodynamic therapy. Under ultrasound/photoacoustic imaging guidance, we induced on-the-spot bubble explosion and photodynamic therapy of tumors at a depth of centimeters in vivo. The mechanical impact of the explosion can enhance delivery of the photosensitizers. Ultrasound explicitly revealed the cancer morphology and exhibited fast NB perfusion. Generated mechanical damage and release of mixture agents demonstrated remarkable synergetic anticancer effects on deep tumors. This finding also offers a new approach and insight into treating cancers.