Deep Tissue Research Articles

Multi-Objective Design of DNA-Stabilized Nanoclusters Using Variational Autoencoders With Automatic Feature Extraction.

DNA-stabilized silver nanoclusters (AgN-DNAs) have sequence-tuned compositions and fluorescence colors. High-throughput experiments together with supervised machine learning models have recently enabled design of DNA templates that select for AgN-DNA properties, including near-infrared (NIR) emission that holds promise for deep tissue bioimaging. However, these existing models do not enable simultaneous selection of multiple AgN-DNA properties, and require significant expert input for feature engineering and class definitions. This work presents a model for multiobjective, continuous-property design of AgN-DNAs with automatic feature extraction, based on variational autoencoders (VAEs). This model is generative, i.e., it learns both the forward mapping from DNA sequence to AgN-DNA properties and the inverse mapping from properties to sequence, and is trained on an experimental data set of DNA sequences paired with AgN-DNA fluorescence properties. Experimental testing shows that the model enables effective design of AgN-DNA emission, including bright NIR AgN-DNAs with 4-fold greater abundance compared to training data. In addition, Shapley analysis is employed to discern learned nucleobase patterns that correspond to fluorescence color and brightness. This generative model can be adapted for a range of biomolecular systems with sequence-dependent properties, enabling precise design of emerging biomolecular nanomaterials.

Safety and Efficacy of an Injectable Solution Enriched With Sodium Hyaluronate, Amino Acids, and Peptides in Relation to Superficial Facial Connective Tissues (Dermis and Retinacular Cutis).

Skin aging research often focuses on the dermis, overlooking the significance of the retinacular cutis (RC) in aging. This study aimed to investigate the efficacy, safety, and effect of an injectable solution containing hyaluronic acid, amino acids, and peptides, on facial sagging and laxity by targeting the RC. This single-center observational study recruited 28 female volunteers aged 25-65 years. The participants received four monthly injections of the studied solution. Objective measures included skin hydration, elasticity, color, thickness, collagen density evaluated via DermaLab Combo and high-resolution ultrasound imaging. Subjective measures included participant satisfaction evaluated using the Global Aesthetic Improvement Scale (GAIS). Adverse effects were monitored throughout the study period. Significant improvements were observed in skin hydration, elasticity, and collagen density after treatment. Hydration increased by 25.9% at T1 (30 days after last session), sustaining a 15.9% increase at T2 (120 days after last session). Elasticity improved by 29.2% at T1 and 20.7% at T2. Collagen density increased by 20.27% at T1 and 16.71% at T2. Self-reported GAIS scores showed consistent increases. Adverse effects were minimal and included only transient ecchymosis and mild pain. Injections of the solution had a substantial hydrating effect, enhanced elasticity, and increased collagen density in the RC and dermis. Results persisted at the 120-day follow-up, indicating sustained benefits. Hence, this injectable solution may offer a safe and effective non-invasive treatment option for improving skin laxity and sagging, targeting the RC and other deep connective tissue such as retaining ligaments.

A Water‐Soluble Fluorescent Probe Derived from Pyridine‐2,6‐Dicarboxylic Acid: Synthesis, Interaction with Ions, and Two‐Photon Microscopy

AbstractTwo‐photon excited fluorescence is a process in which the excited fluorophore relaxes and emits fluorescence after two‐photon absorption. Combined with appropriate two‐photon fluorescent probes, two‐photon microscopy enables observation deep inside tissue without damage. Former reports showed that the two‐photon absorption cross sections of donor–acceptor (D–A) dipoles, as well as D‐π‐D and D–A–D quadrupoles can be strengthened by using strong D–A groups. In this study, a novel water‐soluble fluorescent probe with D‐π‐A structure containing pyridine‐2,6‐dicarboxylic acid unit was synthesized. The maximum excitation wavelength and emission wavelength of the probe in aqueous solution were 328 nm and 471 nm, respectively. The fluorescence emitted by the probe can be quenched by various metal cations. The pyridyl N and carboxyl O in the probe formed chelates with Cu2+, which resulted in a fluorescence quenching response, and showed a linear relationship between fluorescent intensity and Cu2+ concentration with wide linear range and low limit of detection. CCK‐8 tests showed the probe had no obvious toxicity to 4T1 cells in the range of 0.4–50 μmol L−1, and the cell survival rate was above 86 %. The probe had a large two‐photon absorption cross section ranging from 680 nm to 820 nm. The two‐photon absorption cross section reached 100 GM at 760 nm of excitation wavelength. By means of microscopic imaging of 4T1 cells stained with the probe, one‐photon fluorescence represented blue emission, while two‐photon fluorescence represented bright green emission. The probe was proved to have good cell permeability, and preferred to target nucleus, showing application potential in two‐photon fluorescence imaging technology.

A low-voltage-driven MEMS ultrasonic phased-array transducer for fast 3D volumetric imaging

Wearable ultrasound imaging technology has become an emerging modality for the continuous monitoring of deep-tissue physiology, providing crucial health and disease information. Fast volumetric imaging that can provide a full spatiotemporal view of intrinsic 3D targets is desirable for interpreting internal organ dynamics. However, existing 1D ultrasound transducer arrays provide 2D images, making it challenging to overcome the trade-off between the temporal resolution and volumetric coverage. In addition, the high driving voltage limits their implementation in wearable settings. With the use of microelectromechanical system (MEMS) technology, we report an ultrasonic phased-array transducer, i.e., a 2D piezoelectric micromachined ultrasound transducer (pMUT) array, which is driven by a low voltage and is chip-compatible for fast 3D volumetric imaging. By grouping multiple pMUT cells into one single drive channel/element, we propose an innovative cell–element–array design and operation of a pMUT array that can be used to quantitatively characterize the key coupling effects between each pMUT cell, allowing 3D imaging with 5-V actuation. The pMUT array demonstrates fast volumetric imaging covering a range of 40 mm × 40 mm × 70 mm in wire phantom and vascular phantom experiments, achieving a high temporal frame rate of 11 kHz. The proposed solution offers a full volumetric view of deep-tissue disorders in a fast manner, paving the way for long-term wearable imaging technology for various organs in deep tissues.

Comparison of the safety and efficacy of three superficial skin closure methods for multi-layer wound closure in total knee arthroplasty: a multicenter, prospective, randomized controlled trial

BackgroundGood wound healing is critical to infection prophylaxis and satisfactory rehabilitation in Total Knee Arthroplasty (TKA). Currently, two techniques, i.e., barbed continuous subcuticular suture without skin adhesive or combined use skin adhesive (n-butyl-2) are being used for superficial wound closure of TKA. While a new skin adhesive (2-octyl) with self-adhesive mesh has been employed as an alternative to conventional surgical skin closure in TKA, its superiority, especially in reducing wound complications and improving wound cosmetic outcomes has not been investigated. This study aimed to compare 2-octyl, n-butyl-2, and no skin adhesive in terms of safety and efficacy in TKA superficial wound closure.MethodsWe conducted a multicenter, prospective, randomized controlled study in 105 patients undergoing primary TKA between May 2022 and October 2023. Each patient’s knee was randomized to receive 2-octyl, n-butyl-2, or no skin adhesive skin closure with all using barbed continuous sutures in deep tissue. Wounds were followed 1, 3, 5 days, 2, 6 weeks, and 3 months after surgery. Wound discharge, complications, cosmetic outcomes, patient satisfaction, and wound-related costs were compared among these three methods.ResultsWound discharge was less in 2-octyl group and n-butyl-2 group than in non-adhesive group at 1 day, with the discharge only being less in 2-octyl group than in the non-adhesive group at day 3 and day 5 days (P < 0.05). There was no statistical difference in the incidence of other wound complications among the groups (P > 0.05). The 2-octyl group achieved better cosmetic effects than the other two groups in 6 weeks and 3 months (P < 0.05). Compared to the non-adhesive group, 2-octyl group scored higher in overall patient satisfaction score in 2 weeks and incurred lower costs (P < 0.05).ConclusionsSkin closure in TKA using 2-octyl adhesive material showed superiority when compared to no skin adhesive or n-butyl-2, in reducing wound discharge, improving the cosmetic outcomes, without increasing wound complications. In addition, the use of 2-octyl yielded better patient satisfaction and also was less costly compared to no skin adhesive. Our study exhibited that 2-octyl was a safe and effective wound closure technique for patients undergoing TKA.Trial registrationThis study has been registered at Clinical Trials. Gov (No. ChiCTR210046442).

Deep Mouse Brain Two-Photon Near-Infrared Fluorescence Imaging Using a Superconducting Nanowire Single-Photon Detector Array.

Two-photon microscopy (2PM) has become an important tool in biology to study the structure and function of intact tissues in vivo. However, adult mammalian tissues such as the mouse brain are highly scattering, thereby putting fundamental limits on the achievable imaging depth, which typically reside at around 600-800 μm. In principle, shifting both the excitation as well as (fluorescence) emission light to the shortwave near-infrared (SWIR, 1000-1700 nm) region promises substantially deeper imaging in 2PM, yet this shift has proven challenging in the past due to the limited availability of detectors and probes in this wavelength region. To overcome these limitations and fully capitalize on the SWIR region, in this work, we introduce a novel array of superconducting nanowire single-photon detectors (SNSPDs) and associated custom detection electronics for use in near-infrared 2PM. The SNSPD array exhibits high efficiency and dynamic range as well as low dark-count rates over a wide wavelength range. Additionally, the electronics and software permit a seamless integration into typical 2PM systems. Together with an organic fluorescent dye emitting at 1105 nm, we report imaging depth of >1.1 mm in the in vivo mouse brain, limited mostly by available labeling density and laser properties. Our work establishes a promising, and ultimately scalable, new detector technology for SWIR 2PM that facilitates deep tissue biological imaging.

High-fidelity imaging of drug-induced acute gastritis by using a fluorescent and photoacoustic dual-modal probe with good stability in stomach acid

In consideration of deep tissue imaging and signal fidelity, fluorescent-photoacoustic (PA) dual-modal probes are much more desirable. However, dual-modal imaging of gastritis using molecular probes remains a challenge due to the harsh gastric acid environment in the stomach. Based on the positive correlation between gastritis and cell viscosity, stomach acid-stable and viscosity-activated probes could potentially diagnose gastritis. As a proof of concept, herein, a fluorescent and photoacoustic dual-modal probe (named WSP-1) is revealed for the imaging of drug-induced acute gastritis in vivo. WSP-1 exhibits viscosity-dependent fluorescence emission and photoacoustic signals. A rotatable C–C single bond is incorporated into the D-π-A structure of WSP-1, which could facilitate the formation of the twisted intramolecular charge transfer (TICT) state in a low-viscosity environment (weak fluorescence/PA signal) and the intramolecular charge transfer (ICT) state in a high-viscosity environment (strong fluorescence/PA signal). WSP-1 has demonstrated the capability to target mitochondria and can be utilized to monitor the viscosity enhancement of cells during inflammation. Most importantly, WSP-1 exhibits good optical and structural stability in gastric acid. By leveraging these desirable features of WSP-1, we have achieved fluorescent and 3D photoacoustic in situ imaging of drug-induced acute gastritis following oral administration of WSP-1.

Research Progress of Cyanine-based Near-Infrared Fluorescent Probes for Biological Application.

Cyanine-based near-infrared (NIR) fluorescent probes have played vital roles in biological application due to their low interference from background fluorescence, deep tissue penetration, high sensitivity, and minimal photodamage to biological samples. They are widely utilized in molecular recognition, medical diagnosis, biomolecular detection, and biological imaging. Herein, we provide a review of recent advancements in cyanine-based NIR fluorescent probes for the detection of pH, cells, tumor as well as their application in photothermal therapy (PTT) and photodynamic therapy (PDT).

Discovering the potential of biomaterial-based mesoporous and magneto-luminescent nanohybrid (Nd-doped Hydroxyapatite/Fe3O4) for cancer theragnosis

Multimodality nanoplatforms play a crucial role in advancing medical interventions by integrating multiple functionalities into a single system. However, issues like intricate production processes and biocompatibility persist. Herein, a facile synthesis of a biomaterial-based mesoporous nanocarrier, HAp:Nd+SPIONs@mSiO2 is reported. The nanohybrid with ∼100 nm average size, comprised of Nd-doped hydroxyapatite (HAp:Nd) nanophosphor, Fe3O4 superparamagnetic iron oxide nanoparticles (SPIONs), and mesoporous silica, exhibiting magneto-luminescent properties. The nanohybrid showed NIR to NIR photoluminescence properties important for deep tissue imaging. The mesoporous nanohybrid was loaded with Indocyanine green (ICG), a photosensitizer and photothermal dye, as a model drug (∼6 μg/mg of nanoparticles) with a high absorption stability retaining >75 % drug until 24 h incubation in pH 6 and 7.4, respectively. Nanoparticles demonstrated dual functionality by generating heat through magnetic and photonic stimulation, as well as producing reactive oxygen species (ROS) upon excitation with 808 nm light. In vitro assays on aggressive triple-negative breast cancer cells (MDA-MB-231) showed the high biocompatibility of nanohybrid with and without ICG, while a significant toxicity was seen after irradiation of NIR light due to ROS production. Noticeably, the nanohybrids also exhibit the ability to monitor temperature changes via Nd3+ associated NIR luminescence. The nanoplatform integrates clinically relevant components like hydroxyapatite, SPIONs, mesoporous silica and ICG, highlighting its potential for translational applications. The developed nanohybrids, with combined NIR-mediated photothermal and photodynamic effects, magnetic photothermal capabilities, and NIR/MR imaging, offer promise in addressing cancer heterogeneity and improving conventional treatments with reduced side effects.

Construction of Through‐Space Charge‐Transfer Nanoparticles for Facilely Realizing High‐Performance NIR‐II Cancer Phototheranostics

AbstractPhototheranostics with second near‐infrared (NIR‐II) emissions show great potential for disease diagnosis and imaging‐guided phototherapy owing to deep tissue penetration, high imaging resolution, and excellent tumor eradication. Recently, molecular conjugation engineering and J‐aggregation have been used to construct organic NIR‐II materials. However, these molecules generally have extensive conjugation and large molecular weight in the range of 700–1700 g mol−1, requiring complicated molecular design and synthesis. Herein, a NIR‐II emissive through‐space charge‐transfer (TSCT) nanoparticle (NP) using short‐conjugated donor‐acceptor (D‐A) molecules (TTP) is reported for high‐performance bioimaging and cancer phototheranostics. Owing to the short conjugation of the TTP molecule with a small molecular weight of only 518 g mol−1, the TTP monomer possesses visible absorption and first near‐infrared (NIR‐I) emission. Upon forming NPs in water, the efficient TSCT between TTP monomers leads to significantly red‐shifted absorption to the NIR‐I and emission to the NIR‐II region with a tail that extends to 1400 nm. TTP NPs are employed in NIR‐II in vivo blood‐vessel bioimaging and cancer phototheranostics successfully. This work introduces a facile strategy to construct NIR‐II emissive NPs based on short‐conjugated D‐A molecules for high‐performance biomedical applications.

Three Photon Excited Image Scanning Microscopy for in-Depth Super-Resolution Studies of Biological Samples

Multiphoton laser scanning microscopy is a powerful tool for deep imaging of thick biological samples. Image scanning microscopy (ISM) has demonstrated significant improvements in the signal-to-noise ratio in confocal laser scanning microscopy, while at the same time improving upon the effectively attainable resolution. Two-photon excitation (2PE), combined with ISM, has been shown to allow for deep tissue imaging with enhanced resolution compared to 2PE microscopy. Three-photon excitation (3PE) has enabled record imaging depth and contrast for multiphoton imaging, due to the superior suppression of out-of-focus signal generation. In this paper, we demonstrate super-resolution 3PE ISM. This is achieved using a single-photon avalanche detector array, and 1040-nm pulses for 3PE of blue fluorescence. This method enables subdiffraction limited resolution imaging of biological samples stained with blue fluorescent markers, such as mouse myocardial and spinal cord tissues stained with 4′,6-diamidino-2-phenylindole. Deconvolution improves the resolving power further and allows for imaging with better than λ/8 resolution with respect to the 3PE wavelength λ. With the ISM pixel reassignment procedure, we demonstrate a resolution enhancement of ∼1.6 laterally, compared to the resolution attained using a photomultiplier tube in a non-descanned detection arrangement, and a factor of ∼1.8 enhancement in axial resolution. The experimentally measured three-dimensional point spread function volume is shrunk ∼4.4-fold, which is close to the theoretically expected enhancement. Published by the American Physical Society 2024

Choke Anastomosis: A Key Element Acting as a Shunt Converter Between Adjacent Angiosomes.

Choke anastomosis is commonly recognized as a resistance factor that detrimentally affects the hemodynamics of the skin flap; however, its additional potential physiological roles in normal skin function are currently not fully understood. Ten cadaveric forehead flap specimens pedicled with unilateral STAs were perfused with lead oxide-gelatin mixture, and then dissected into 3 layers, including the super temporal fascia-frontalis-galea aponeurotica layer, the subcutaneous adipose tissue layer, and the "super-thin flap" layer. The forehead flap and stratified specimens underwent molybdenum target x-ray and subsequent transparent processing to effectively visualize the microscopic spatial architecture of arterial vessels across all levels. Based on the different anastomoses near the midline area of the flap, 2 types of arterial perfusion were identified: choke anastomosis type (8/10) and true anastomosis type (2/10). The former formed multiple choke anastomoses near the midline. In the "super-thin flap" layer, arterial perfusion density on the ipsilateral side was significantly higher compared to that on the contralateral side. The arterioles on the ipsilateral side exhibited a dense and uninterrupted distribution, whereas those on the contralateral side appeared sparse and dispersed. The latter exhibited an alternative perfusion pattern; the bilateral arterial vessels were connected with 3 to 5 true anastomoses near the midline. Furthermore, the microscopic architecture confirmed a uniform distribution of arterioles that remained continuous from ipsilateral to contralateral sides in the "super-thin flap" layer. This study demonstrated that choke anastomosis not only impairs blood perfusion in the adjacent angiosomes but also acts as a shunt converter to impact the blood supply of distal skin flaps at different levels through the "trans-territory diversion phenomenon." This results in necrosis of the superficial dermis while preserving survival of the deep subcutaneous adipose tissue.

Dual-Locked Probe with Activatable Sonoafterglow Luminescence for Precise Imaging of MET-Induced Liver Injury.

Metformin (MET) is currently the first-line treatment for type 2 diabetes mellitus (T2DM). However, overdose and long-term use of MET may induce a serious liver injury. What's worse, diagnosis of MET-induced liver injury remains challenging in clinic. Although several probes have been reported for imaging MET-induced liver injury utilizing upregulated hepatic H2S as a biomarker, they are still at risk of nonspecific activation in complex physiological environments and rely on light excitation with limited imaging depth. Herein, we rationally designed and developed a dual-locked probe, DPA-H2S, for precise imaging of MET-induced liver injury by H2S-activated sonoafterglow luminescence. DPA-H2S is a small molecule consisting of a sonosensitizer protoporphyrin IX (PpIX) and an afterglow substrate that is dual-locked with a H2S-responsive 2,4-dinitrobenzene group and a 1O2-responsive electron-rich double bond. When employing DPA-H2S for imaging of MET-induced liver injury in vivo, since the PpIX moiety can produce 1O2 in situ at the liver site under focused ultrasound (US) irradiation, the two locks of DPA-H2S can be specifically activated by the highly upregulated H2S at the liver injury sites and the in situ generated 1O2, respectively. Thus, the sonoafterglow signal of DPA-H2S is significantly turned on, enabling precise imaging of the MET-induced liver injury. In vitro results showed that, through H2S-activated sonoafterglow luminescence, DPA-H2S was capable of imaging H2S with good sensitivity and high selectivity and realized deep tissue imaging (∼20 mm, signal-to-background ratio (SBR) = 3.4). Furthermore, we successfully applied DPA-H2S for precise in vivo imaging of MET-induced liver injury. We anticipate that our dual-locked probe, DPA-H2S, may serve as a promising tool in assisting the diagnosis of MET-induced liver injury in clinics and informing the clinical utilization of MET in the near future.

Sustained acoustic medicine treatment of discogenic chronic low back pain: A randomized, multisite, double-blind, placebo-controlled trial.

Sustained acoustic medicine (SAM) is a noninvasive long-term treatment that provides essential mechanical and thermal stimulus to accelerate soft tissue healing, alleviate pain, and improve physical activity. SAM increases localized deep tissue temperature, blood flow, cellular proliferation, migration, and nutrition exchange, resulting in reduced inflammation and an increased rate of tissue regeneration. To assess the efficacy of SAM treatment of discogenic back pain in the lower spinal column to reduce pain, improve quality of life, and lower pharmacotherapy use. Sixty-five subjects with chronic low back pain were randomly assigned to SAM (N= 33) or placebo (N= 32) groups. Subjects self-applied SAM device bilaterality on the lower lumbar region for 4 hours daily for 8 weeks and completed daily pain diaries before, during, and after treatment. Subjects recorded pain reduction using a numeric rating scale (NRS), medication use, and physical activity using the Global Rating of Change (GROC) and Oswestry Disability Index (ODI). SAM treatment significantly reduced chronic lower back pain from baseline relative to placebo treatment (p< 0.0001). SAM treated subjects reported significantly lower back pain at 4 weeks, with the highest pain reduction (-2.58 points NRS, p< 0.0001) reported at 8 weeks. Similar trends were observed in improved physical activity (3.48 GROC, p< 0.0001, 69-88% ODI, p< 0.0001) and 22.5% (15.2 morphine milligram equivalent) reduction in the use of opioid medication from baseline to 8 weeks. Daily, home-use SAM treatment significantly improves the clinical symptoms of chronic lower back pain, improves physical mobility, and reduces daily medication use. SAM treatment is well-tolerated by patients and may be considered a safe, non-invasive treatment option for chronic discogenic, lower back pain.

Antibiotic sensitivity pattern of deep skin and soft tissue infections in Pakistan.

Objective: To determine the antibiotic spectrum of deep skin and soft tissue infections in Pakistan. Study Design: Cross-sectional study. Setting: Department of Dermatology at Madinah Teaching Hospital, Faisalabad. Period: June, 2023 to December 2023. Methods: Inclusion criteria covered consenting patients aged 15-60, excluding those with specific conditions. The study aimed to ascertain antibiotic sensitivity patterns in deep skin and soft tissue infections. Ethical approval was obtained, and subjects meeting criteria were enrolled after informed consent, contributing valuable insights into healthcare-associated infections. Results: Examining 60 patients, the age distribution indicates a prevalent cohort up to 50 years (61.7%), highlighting potential health concerns in earlier years. Those above 50 constitute 38.3%, signifying distinct challenges in older age. With 61.7% males, Gram stain analysis reveals microbial diversity. Notably, Ciprofloxacin (90%) and Cefipime (98.3%) exhibit high resistance, while Cephradine (48.3%) and Cefoxitin (20%) show sensitivity. Meropenem and Vancomycin display moderate resistance (28.3% and 25%), while Tigecycline (10%) and Teicoplanin (1.7%) exhibit lower resistance, offering insights for effective treatment strategies. Conclusion: Our study reveals notable antibiotic resistance, with Ciprofloxacin (90%) and Cefipime (98.3%) exhibiting high resistance. Conversely, Cephradine (48.3%) and Cefoxitin (20%) show sensitivity, guiding tailored treatment strategies for deep skin and soft tissue infections.

Use of Fresh Frozen Plasma in a Dramatic Case of ACE-Inhibitor Associated Angioedema

Angioedema describes a non-dependent, non-pitting and transient edema caused by the accumulation of vasoactive substances in the circulation. These vasoactive substances increase vascular permeability, causing swelling of the deep dermal, submucosal or subcutaneous tissues of the face, lips, neck, extremities or gastrointestinal tract. Urticaria may or may not accompany this condition. Angioedema is generally mediated through two pathways: histamine-mediated and bradykinin-mediated. Histamine-mediated angioedema generally responds to standard therapeutic measures (such as antihistamines, steroids and epinephrine), whereas bradykinin-mediated angioedema can be more difficult to manage in emergency departments (ED). Here, we present a patient who presented to our ED with bradykinin-mediated ACE-I-associated dramatic angioedema clinic, did not respond to standard treatments, rapidly improved with fresh frozen plasma (FFP) administration and was discharged after 6 days of follow-up in the emergency critical intensive care unit.

The Feasibility Study of Bone Fracture Assessment Based on Photoacoustic Time-of-Flight Method

Abstract Photoacoustic imaging (PAI) technology combines the advantages of acoustic resolution and optical contrast imaging within deep tissue. The commonly clinically used bone fracture detection and evaluation method is X-ray based imaging techniques. In order to study the feasibility of human radius fractures detection in non-radiation and non-invasive way, this study combined the time-of-flight (TOF) method commonly used in industrial nondestructive testing with photoacoustic technology for the detection and location of bone fractures. Firstly, the bone fracture information carried by PA signal was studied by simulating the bone models with different locations of bone fractures. The finite difference time domain (FDTD) method was used to simulate the propagation process of photoacoustic signal in bone tissue. Secondly, the PATOF diagrams formed by PA signals at different locations is obtained by using laser fixed and ultrasonic detector motion detection method. Finally, the PATOF diagrams are further analyzed and quantified. The results show that the photoacoustic bone detection method based on TOF method can effectively locate the fracture location. This study confirms the feasibility of combining PAI technique with TOF method to detect bone fractures, which indicates that PAI technique has great application prospect in bone detection field.

An inter-assessor reliability study on the categorization and staging of pressure injuries

BackgroundThe first step in effective management of pressure injuries (PIs) is to assess, categorize and stage correctly. PurposeThis study aims to examine the agreement regarding the classification and staging of PIs among nurse academicians working on chronic wounds and with different stage of expertise. MethodsThree nurse academicians were assigned as assessors according to Benner's stages of clinical competence (Competent, Proficient, and Expert). The assessors independently evaluated PIs photographs (n = 694). The assessors then met for the wounds where there was disagreement, and a Consensus agreement was reached. Kappa Statistics analysed the agreement between two assessors; Fleiss Kappa Statistics analysed the agreement between Competent, Proficient, Expert, and Consensus. ResultsStatistically, almost perfect agreement was obtained between Competent, Proficient, Expert, and Consensus assessments, respectively (Ƙ = 0.871; p < 0.001, Ƙ = 0.842; p < 0.001, Ƙ = 0.937; p < 0.001). The highest agreement between the assessors were Unstageable PIs, Deep Tissue PIs, and Stage 3 PIs respectively. The most common disagreements were between Deep Tissue PIs and Stage 1 PIs, and between Deep Tissue PIs and Stage 2 PIs. ConclusionIn the study, it was found that the categorization, and staging of PIs had varying degrees of reliability among the assesors, although at a statistically acceptable level.

Microneedle-based arrays – Breakthrough strategy for the treatment of bacterial and fungal skin infections

Currently, fungal and bacterial skin infections rank among the most challenging public health problems due to the increasing prevalence of microorganisms and the development of resistance to available drugs. A major issue in treating these infections with conventional topical medications is the poor penetration through the stratum corneum, the outermost layer of the skin. The concept of microneedles seems to be a future-proof approach for delivering drugs directly into deeper tissues. By bypassing the skin barrier, microneedle systems allow therapeutic substances to reach deeper layers more efficiently, significantly improving treatment outcomes. Nonetheless, the primary challenges regarding the effectiveness of microneedles involve selecting the appropriate size and shape, along with polymer composition and fabrication technology, to enable controlled and efficient drug release. This review offers a comprehensive overview of the latest knowledge on microneedle types and manufacturing techniques, highlighting their potential effectiveness in treating bacterial and fungal skin infections. It includes updated statistics on infection prevalence and provides a detailed examination of common bacterial and fungal diseases, focusing on their symptoms, causative species, and treatment methods. Additionally, the review addresses safety considerations, regulatory aspects, and future perspectives for microneedle-based therapeutic systems. It also underscores the importance of industrialization and clinical translation efforts, emphasizing the significant potential of microneedle technology for advancing medical applications.

Colon-specific controlled release of oral liposomes for enhanced chemo-immunotherapy against colorectal cancer

A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating Clostridium butyricum spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into Clostridium butyricum (CB) and colonized in the colon. Combined with colonic specifically β-glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8+ T cells and reactivated robust antitumor immunity.