Highly thermal stable RNase A@PbS/ZnS quantum dots as NIR-IIb image contrast for visualizing temporal changes of microvasculature remodeling in flap.

Surgeons face great challenges in acquiring high-performance imaging because fluorescence probes with desired thermal stability remains rare. Here, hybrid lead sulfide/zinc sulfide quantum dots (PbS/ZnS QDs) nanostructures emitting in the long-wavelength end of the second near-infrared (NIR-IIb) window were synthesized and conjugated with Ribonuclease-A (RNase A). Such formed RNase A@PbS/ZnS QDs exhibited strong NIR IIb fluorescence and thermal stability, as supported by the photoluminescent emission assessment at different temperatures. This will allow the RNase A@PbS/ZnS QDs to provide stable fluorescence signals for long-time intraoperative imaging navigation, despite often happened, undesirable thermal accumulation in vivo. Compared to NIR-IIa fluorescence imaging, NIR-IIb vascular fluorescence imaging achieved larger penetration depth, higher signal/background ratios and nearly zero endogenous tissue autofluorescence. Moreover, these QDs illustrate the reliability during the real-time and long-time precise assessment of flap perfusion by clearly visualizing microvasculature map. These findings contribute to intraoperative imaging navigation with higher precision and lower risk.

Bankart Repair With Remplissage Restores Better Shoulder Stability Than Bankart Repair Alone, and Medial or Two Remplissage Anchors Increase Stability but Decrease Range of Motion: A Finite Element Analysis.

PURPOSE: To investigate the effects of the number and location of anchors for remplissage on postoperative glenohumeral biomechanics. METHODS: A biomechanical study was conducted involving finite element model constructed based on data from the intact glenohumeral joint. Seven models were established, including a normal model, a model of Bankart lesion combined with "off-track" Hill-Sachs lesion, a model of Bankart repair alone, and 4 models of Bankart repair with remplissage based on different remplissage anchor numbers and locations. The effects of the number and location of the remplissage anchors on glenohumeral stability were studied through calculation and comparison of (1) the stress and its distribution on the joint capsule, cartilage, labrum and anchors as well as (2) the displacement of the humeral head. RESULTS: Finite element analysis demonstrated that contact stress on the glenohumeral cartilage decreased when medial or 2 anchors were used and was minimized in the combined repair model with 2 medial anchors. The stress on remplissage anchors was greater when the anchors were placed medially. The humeral head displacement was maximized in the combined lesion model. The combined repair models with 2 medially placed anchors showed the largest slope on the force-displacement curve, indicating the largest strain on the humeral head. CONCLUSIONS: Based on a finite element analysis, Bankart repair with remplissage restored better shoulder stability compared with Bankart repair alone in the treatment of anterior shoulder instability involving Bankart lesion combined with "off-track" Hill-Sachs lesion. When the anchor for remplissage was medially placed or 2 anchors were used, the stability of the glenohumeral joint increased but with a loss of range of motion. CLINICAL RELEVANCE: The results of this study will assist in choosing the number and location of anchors for remplissage during shoulder stabilization surgery although with some limitations.

Stretchable multifunctional hydrogels for sensing electronics with effective EMI shielding properties.

Hydrogel-based soft and stretchable materials with skin/tissue-like mechanical properties provide new avenues for the design and fabrication of wearable sensors. However, synthesizing multifunctional hydrogels that simultaneously possess excellent mechanical, electrical and electromagnetic interference (EMI) shielding effectiveness is still a great challenge. In this work, the freeze-casting method is employed to fabricate a multifunctional hydrogel by filling Fe3O4 clusters into poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid) (PEDOT:PSS) and polyvinyl alcohol (PVA) composite aqueous solution. The hydrogel possesses superior electrical and mechanical properties as well as great electromagnetic wave shielding properties. Benefiting from the high stretchability (∼904.5%) and fast sensing performance (response time ∼9 ms and self-recovery time ∼12 ms within the strain range ∼100%), the monitoring of human activities and manipulation of a remote-controlled toy car using the hydrogel-based stretchable strain sensors are successfully demonstrated. In addition, a great EMI shielding effectiveness with more than 46 dB in the frequencies of 8-12.5 GHz can be obtained, which provides an alternative strategy for designing next-generation EMI shielding materials. These results indicate that the multifunctional hydrogels can be used as flexible and stretchable sensing electronics requiring effective EMI shielding.

Interfacial Mo-N-C Bond Endowed Hydrogen Evolution Reaction on MoSe2@N-Doped Carbon Hollow Nanoflowers.

Molybdenum diselenide (MoSe2) has been considered as promising electrocatalysts for catalyzing the hydrogen evolution reaction (HER) due to its narrow band gap and appropriate adsorption free energy. However, its catalytic performance is still impeded by inferior electrical conductivity and insufficient active sites, thus leading to unsatisfactory HER performance. Herein, MoSe2@N-doped carbon (NC) hollow nanoflowers with interfacial Mo-N-C bonds were controllably fabricated through the in situ selenization of the self-polymerized Mo-polydopamine precursor. Benefiting from the unique hollow structure, NC protective layer, and intimate interfacial interaction, the optimal MoSe2@NC displays good HER performance with low overpotentials (175 and 183 mV) and long-term stability (up to 12 h at -10 mA cm-2) in 0.5 M H2SO4 and 1.0 M KOH solutions, respectively. The theoretical results show that Mo-N-C bonds at the interface of MoSe2@NC give rise to relatively low unoccupied eg orbital density of states and ideal H2 adsorption free energy. This work presented here highlights the critical role of interfacial chemical bonds in regulating the electronic structure of nanomaterials and further improving the HER performance.

In Vivo Dynamic Monitoring of Bacterial Infection by NIR-II Fluorescence Imaging.

Time window of antibiotic administration is a critical but long-neglected point in the treatment of bacterial infection, as unnecessary prolonged antibiotics are increasingly causing catastrophic drug-resistance. Here, a second near-infrared (NIR-II) fluorescence imaging strategy based on lead sulfide quantum dots (PbS QDs) is presented to dynamically monitor bacterial infection in vivo in a real-time manner. The prepared PbS QDs not only provide a low detection limit (104 CFU mL-1 ) of four typical bacteria strains in vitro but also show a particularly high labeling efficiency with Escherichia coli (E. coli). The NIR-II in vivo imaging results reveal that the number of invading bacteria first decreases after post-injection, then increases from 1 d to 1 week and drop again over time in infected mouse models. Meanwhile, there is a simultaneous variation of dendritic cells, neutrophils, macrophages, and CD8+ T lymphocytes against bacterial infection at the same time points. Notably, the infected mouse self-heals eventually without antibiotic treatment, as a robust immune system can successfully prevent further health deterioration. The NIR-II imaging approach enables real-time monitoring of bacterial infection in vivo, thus facilitating spatiotemporal deciphering of time window for antibiotic treatment.

The Effects of Angelica Sinensis Polysaccharide on Tumor Growth and Iron Metabolism by Regulating Hepcidin in Tumor-Bearing Mice.

BACKGROUND/AIMS: Iron plays a fundamental role in cell biology and its concentration must be precisely regulated. It is well documented that excess iron burden contributes to the occurrence and progression of cancer. Hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. In the present study, we aimed to investigate the ability of angelica sinensis polysaccharide (ASP) to decrease iron burden in tumor-bearing mice and the mechanism of ASP regulation hepcidin expression. METHODS: Western blot, RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulation of hepcidin and related cytokines by ASP. The role of ASP in tumor proliferation was investigated using in vivo assays. Iron depositions and iron concentrations in organs were determined by hematoxylin-eosin (H&E) staining and atomic absorption spectrophotometer. RESULTS: We found that ASP could inhibit tumor growth in mice xenografted with 4T1 and H22 cancer cells. In vivo experiments also showed that ASP could potently regulate hepcidin expression in liver and serum and decrease iron burden in liver, spleen and grafted tumors in mouse model. Treatment with ASP in hepatic cell lines reproduced comparable results in decreasing hepcidin as in mouse liver. Furthermore, we found that ASP markedly suppressed the expression of interleukin-6 (IL-6), JAK2, p-STAT3, and p-SMAD1/5/8 in liver, suggesting that JAK/STAT and BMP-SMAD pathways were involved in the regulation of hepcidin expression by ASP. We also found down-regulation of iron-related cytokines in ASP treated mice. CONCLUSION: The present study provides new evidence that ASP decreases hepcidin expression, which can reduce iron burden and inhibit tumor proliferation. These findings might aid ASP developed as a potential candidate for cancer treatment in patients with iron overload.

MPEG-PCL Copolymeric Micelles for Encapsulation of Azithromycin.

Macrolide antibiotics are lipophilic drugs with some limitations including low solubility, limited cellular permeation, patients discomfort, etc. With amphiphilic methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-PCL) copolymer and azithromycin (AZT) as drug carrier and model drug, AZT-loaded micelles were prepared via thin-membrane hydration method in order to overcome these limitations. Encapsulation efficiency of AZT-loaded micelles was 94.40% with good storage stability for 28 days, and AZT's water solubility was enhanced to 944 µg/mL. Fourier transform infrared spectrum and x-ray diffraction analysis indicated that AZT was enveloped into the micelles in amorphous form due to its interaction with the copolymer. AZT's in vitro release from the AZT-loaded micelles demonstrated a slow and continuous behavior when compared with raw AZT. The release dynamics was accorded with Weibull equation, meaning that release amount of AZT lowered with time and was proportional to remaining amount of drug in the AZT-loaded micelles. Korsmeyer-Peppas fitting result suggested that drug release process was a classical Fickian diffusion-controlled manner. With Staphylococcus aureus as bacterial strain, antibacterial activity of the AZT-loaded micelles displayed was comparable with raw AZT. In conclusion, MPEG-PCL should be a promising carrier for macrolide antibiotic delivery in treatment of bacterial infections.

Effect of different non-pharmacologic placebo treatments on migraine prevention: a network meta-analysis of randomized controlled trials.

BACKGROUND: Placebo control plays an important role in evaluating the effectiveness of interventions. Specifying differential effects of various placebo controls on migraine prevention would be essential in the explanation of preventive treatment for migraine and the indirect comparison between different prophylactic therapeutics. OBJECTIVES: To access the impact of different non-pharmacologic placebo types on different outcomes in migraine patients. METHODS: We searched PubMed, Cochrane Controlled Register of Trials, Embase, and Web of Science databases from the date of creation to June 19, 2023. Randomized controlled trials of migraine that included sham intervention of acupuncture or cognitive behavioural therapy (CBT) or non-invasive Vagus Nerve Stimulation (nVNS) or repetitive Transcranial Magnetic Stimulation (rTMS) or transcranial Direct Current Stimulation (tDCS) were conducted. The primary outcome was the migraine days, and the secondary outcomes were the number of migraine attacks, headache days, headache frequency, and responder's rate. Placebo effects were assessed using five individual placebos for network meta-analysis, using mean differences to measure the relative effect of pair-wise comparisons between interventions. RESULT: A total of 50 trials with 4880 subjects were included. Twenty-seven trials were evaluated for low risk of bias. The results of indirect comparisons show that sham rTMS and sham tDCS had optimal and similar effects in reducing migraine days; sham acupuncture has the greatest effect on reducing the number of migraine attacks and relieving headache frequency; sham rTMS had a highly significant advantage in reducing headache days compared with the other placebo controls. CONCLUSION: Based on the network meta-analysis results, we found that sham acupuncture had the greatest effect on migraine prophylaxis. The strong placebo effect of sham acupuncture should be considered when assessing the therapeutic effect.

Single-Dose Radial Extracorporeal Shock Wave Therapy Modulates Inflammation During Meniscal Tear Healing in the Avascular Zone.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) promotes tissue healing by modulating inflammation, which has implications for meniscal tear healing in the avascular zone. PURPOSE: To evaluate the effects of a single dose of radial ESWT on the healing process and inflammation of the meniscus and knee joints after meniscal tears in the avascular zone. STUDY DESIGN: Controlled laboratory study. METHODS: Avascular tears were induced in the medial meniscus (MM) of 72 Sprague-Dawley rats. One week postoperatively, the rats received a single session of radial ESWT with a Power+ handpiece (ESWT group; n = 36) or with a fake handpiece (sham-ESWT group; n = 36). The rats were then euthanized at 2, 4, or 8 weeks postoperatively. The MMs were harvested for analysis of healing (hematoxylin-eosin, safranin O-Fast Green, and collagen type 2 staining) and inflammation (interleukin [IL]-1ß and IL-6 staining). Lateral menisci and synovia were obtained to evaluate knee joint inflammation (enzyme-linked immunosorbent assay of IL-1ß and IL-6). Cartilage degeneration was assessed in the femurs and tibial plateaus using safranin O-Fast Green staining. RESULTS: The ESWT group showed significantly better meniscal healing scores than the sham-ESWT group at 4 (P = .0066) and 8 (P = .0050) weeks postoperatively. The IL-1ß level was significantly higher in the sham-ESWT group than in the ESWT group at 2 (MM: P = .0009; knee joint: P = .0160) and 8 (MM: P = .0399; knee joint: P = .0001) weeks. The IL-6 level was significantly lower in the sham-ESWT group than in the ESWT group at 2 (knee joint: P = .0184) and 4 (knee joint: P = .0247) weeks but higher at 8 weeks (MM: P = .0169; knee joint: P = .0038). The sham group had significantly higher osteoarthritis scores than the ESWT group at 4 (tibial plateau: P = .0157) and 8 (femur: P = .0048; tibial plateau: P = .0359) weeks. CONCLUSION: A single dose of radial ESWT promoted meniscal tear healing in the avascular zone, modulated inflammatory factors in the menisci and knee joints in rats, and alleviated cartilage degeneration. CLINICAL RELEVANCE: Radial ESWT can be considered a potential option for improving meniscal tear healing in the avascular zone because of its ability to modulate inflammation.

Application of Nondegradable Synthetic Materials for Tendon and Ligament Injury.

Tendon and ligament injuries, prevalent requiring surgical intervention, significantly impact joint stability and function. Owing to excellent mechanical properties and biochemical stability, Nondegradable synthetic materials, including polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE), have demonstrated significant potential in the treatment of tendon and ligament injuries. These above materials offer substantial mechanical support, joint mobility, and tissue healing promotion of the shoulder, knee, and ankle joint. This review conclude the latest development and application of nondegradable materials such as artificial patches and ligaments in tendon and ligament injuries including rotator cuff tears (RCTs), anterior cruciate ligament (ACL) injuries, and Achilles tendon ruptures.

Functional and Structural Outcomes After Arthroscopic Rotator Cuff Repair With or Without Preoperative Corticosteroid Injections.

BACKGROUND: Corticosteroid injections (CSIs) are effective in alleviating pain in patients with rotator cuff tears, but controversy still exists regarding their potential adverse effects on clinical outcomes after rotator cuff repair. PURPOSE: To compare both the functional and the structural outcomes in patients who underwent arthroscopic rotator cuff repair with or without preoperative CSIs. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective cohort study was carried out among patients who underwent arthroscopic rotator cuff repair for partial- and full-thickness tears between 2015 and 2019. The patients who received preoperative CSIs were included in the CSI group and compared with a group without preoperative CSIs (non-CSI group), matched at a ratio of 1:2 based on tear size, age, and follow-up time. Both functional evaluation and structural assessments using magnetic resonance imaging (MRI) were performed at the final follow-up. Clinical outcomes-including retear rate as the primary outcome; pain; functional scores including the Constant-Murley score, American Shoulder and Elbow Surgeons score, and Fudan University Shoulder Score; range of motion (ROM); tendon integrity; tendon healing type; and cartilage thickness-were compared between the 2 groups with a statistical significance of P < .05 and power of 0.9. RESULTS: Thirty-one patients were included in the CSI group, and 62 were included in the non-CSI group. After a mean 3-year follow-up, the 2 groups demonstrated no significant differences in retear rate; visual analog scale for pain; shoulder functional scores; and active ROM including forward flexion, abduction, external rotation, and internal rotation. No significant differences were observed on postoperative MRI scans of the rotator cuff tendon (tendon integrity, healing type, residual tendon attachment area, etc), cartilage thickness, and muscle atrophy. CONCLUSION: No significant differences were found at a mean 3-year follow-up in the retear rates, pain, ROM, and glenohumeral structure on postoperative MRI scans after arthroscopic rotator cuff repair with or without preoperative CSIs.

Regional Alterations of Macroscopy and Histology in Meniscus in an ACL Transection Rabbit Model.

BACKGROUND: Although meniscal injury is common after anterior cruciate ligament (ACL) injury, the underlying process in different meniscal regions remains unclear. PURPOSE: To investigate macroscopic and histological alterations in different meniscal regions in an ACL transection (ACLT) rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: ACLT was performed on New Zealand White rabbits. Both the medial meniscus (MM) and the lateral meniscus (LM) of the ACLT knees were obtained at 8 (n = 6) and 26 (n = 6) weeks postoperatively. MM and LM collected from nonoperated knees were considered 0 weeks (n = 6) postoperatively. Menisci were then divided into posterior, central, and anterior regions for macroscopic (width) and histological (hematoxylin and eosin, safranin O/fast green, collagen type 2 [COL2]) analysis. RESULTS: The macroscopic widths of MM and LM increased and then decreased over 26 weeks postoperatively, with all 3 MM widths at 8 weeks significantly wider than at 0 weeks (posterior: P < .01; central: P < .05; anterior: P < .05). In the MM, chondrocyte-like cell density increased and then decreased postoperatively, whereas in the LM, it decreased and then remained almost unchanged. Cell density was significantly higher in the central MM region at 8 weeks than at 0 weeks (P < .05). Glycosaminoglycan (GAG) and COL2 percentages of MM and LM decreased from 0 to 8 weeks and then returned to nearly normal levels at 26 weeks postoperatively. In the MM, the GAG percentage in the posterior (P < .05) and central (P < .01) regions and the COL2 percentage in the posterior region (P < .05) was significantly lower at 8 weeks than at 0 weeks. CONCLUSION: After ACLT in rabbit meniscus, the extracellular matrix (ECM) initially decreased and then increased to almost normal. Additionally, there were significant differences in the ECM percentage in the posterior and central regions of the MM in comparison with other meniscal regions between 0 and 8 weeks postoperatively. CLINICAL RELEVANCE: The results indicate that the time for meniscal injury after ACL injury is important, and attention should be paid to the posterior and central regions of the MM after ACLT.

Probiotics for the management of irritable bowel syndrome: a systematic review and three-level meta-analysis.

OBJECTIVE: Previous systematic reviews demonstrated a potentially beneficial effect of probiotics on irritable bowel syndrome (IBS). However, these studies are either affected by the inclusion of insufficient trials or by the problem of dependent data across multiple outcomes, and an overall effect size has not been provided. We aimed to determine the effect of probiotics on IBS through a three-level meta-analysis and clarify potential effect moderators. METHODS: We searched MEDLINE, Embase, and Web of Science, screening for randomized controlled trials (RCTs) that examine the effect of probiotics on IBS. The primary outcome was the improvement in the severity of global IBS symptoms at the end of treatment. The secondary outcomes were the improvement in abdominal pain and the quality of life. The effect sizes of the probiotics were measured by using the standardized mean difference (SMD) and pooled by a three-level meta-analysis model. RESULTS: We included 72 RCTs in the analysis. The meta-analysis showed significantly better overall effect of probiotics than placebo on the global IBS symptoms (SMD -0.55, 95% CI -0.76 to -0.34, P <0.001), abdominal pain (SMD -0.89, 95% CI -1.29 to -0.5, P <0.001) and quality of life (SMD 0.99, 95% CI 0.45 to 1.54, P <0.001), respectively. Moderator analysis found that a treatment duration shorter than 4 weeks was associated with a larger effect size in all the outcomes, and Bacillus probiotics had better improvement on the abdominal pain. CONCLUSIONS: Probiotics had a short-term effect and a medium effect size on the global IBS symptoms. Treatment duration and types of probiotics affected the effect size of probiotics, and shorter durations and Bacillus probiotics were associated with better treatment effects. REGISTRATION: Open Science Framework.

Efficacy of acupuncture for tension-type headache prophylaxis: systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Acupuncture has been shown to reduce tension-type headache (TTH) frequency in previous studies. Nevertheless, repeated significance testing might inflate type I error. We aimed to verify the effectiveness and safety of acupuncture in reducing TTH frequency by meta-analysis and trial sequential analysis (TSA). METHODS: Ovid Medline, Embase, and Cochrane Library were searched until September 29, 2022. Randomized controlled trials comparing acupuncture with sham acupuncture, no acupuncture, or other active therapies in adults with TTH were included. The primary outcome was TTH frequency. The secondary outcomes were responder rate and adverse event. RESULTS: Fourteen studies involving 2795 participants were included. Acupuncture had more reduction than sham acupuncture in TTH frequency, both after treatment (standardized mean difference [SMD] - 0.80, 95% CI - 1.36 to - 0.24, P = 0.005) and at the follow-up period (SMD - 1.33, 95% CI - 2.18 to - 0.49, P = 0.002), while TSA showed the included sample size did not exceed required information size (RIS). Acupuncture was superior over no acupuncture after treatment (SMD - 0.52, 95% CI - 0.63 to - 0.41, P < 0.001), and cumulative sample size reached RIS. In terms of responder rate, acupuncture had a higher responder rate compared with sham acupuncture both after treatment (relative ratio [RR] 1.28, 95% CI 1.12 to 1.46, P = 0.0003) and the follow-up period (RR 1.37, 95% CI 1.19 to 1.58, P < 0.0001), but the sample size is inadequate. CONCLUSION: Acupuncture is an efficacious and safe treatment for TTH prevention, but this conclusion might be limited by the generally very low to low quality evidence. TSA suggested that high-quality trials are needed to verify the efficacy and safety of acupuncture compared to sham acupuncture.

Three-Dimensional Imaging and Quantitative Analysis of Blood Vessel Distribution in The Meniscus of Transgenic Mouse after Tissue Clearing.

OBJECTIVE: Blood supply to the meniscus determines its recovery and is a reference for treatment planning. This study aimed to apply tissue clearing and three-dimensional (3D) imaging in exploring the quantitative distribution of blood vessels in the mouse meniscus. MATERIALS AND METHODS: In this experimental study, tissue clearing was performed to treat the bilateral knee joints of transgenic mice with fluorescent vascular endothelial cells. Images were acquired using a light sheet microscope and the vascular endothelial cells in the meniscus was analysed using 3D imaging. Quantitative methods were employed to further analyse the blood vessel distribution in the mouse meniscus. RESULTS: The traditional three-equal-width division of the meniscus is as follows: the outer one-third is the red-red zone (RR), the inner one-third is the white-white zone (WW), and the transition area is the red-white zone (RW). The division revealed significant signal differences between the RW and WW (P<0.05) zones, but no significant differences between the RR and RW zones, which indicated that the division might not accurately reflect the blood supply of the meniscus. According to the modified division (4:2:1) in which significant differences were ensured between the adjacent zones, we observed that the width ratio of each zone was 38 ± 1% (RR), 24 ± 1% (RW), and 38 ± 2% (WW). Furthermore, the blood supply to each region was verified. The anterior region had the most abundant blood supply. The fluorescence count in the anterior region was significantly higher than in the central and posterior regions (P<0.05). The blood supply of the medial meniscus was superior to the lateral meniscus (P<0.05). CONCLUSION: Analysis of the blood supply to the mouse meniscus under tissue clearing and 3D imaging reflect quantitative blood vessel distribution, which would facilitate future evaluations of the human meniscus and provide more anatomical references for clinicians.

Current Status and Analysis of Machine Learning in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common tumor. Although the diagnosis and treatment of HCC have made great progress, the overall prognosis remains poor. As the core component of artificial intelligence, machine learning (ML) has developed rapidly in the past decade. In particular, ML has become widely used in the medical field, and it has helped in the diagnosis and treatment of cancer. Different algorithms of ML have different roles in diagnosis, treatment, and prognosis. This article reviews recent research, explains the application of different ML models in HCC, and provides suggestions for follow-up research.

NIR-II live imaging study on the degradation pattern of collagen in the mouse model.

The degradation of collagen in different body parts is a critical point for designing collagen-based biomedical products. Here, three kinds of collagens labeled by second near-infrared (NIR-II) quantum dots (QDs), including collagen with low crosslinking degree (LC), middle crosslinking degree (MC) and high crosslinking degree (HC), were injected into the subcutaneous tissue, muscle and joints of the mouse model, respectively, in order to investigate the in vivo degradation pattern of collagen by NIR-II live imaging. The results of NIR-II imaging indicated that all tested collagens could be fully degraded after 35 days in the subcutaneous tissue, muscle and joints of the mouse model. However, the average degradation rate of subcutaneous tissue (k = 0.13) and muscle (k = 0.23) was slower than that of the joints (shoulder: k = 0.42, knee: k = 0.55). Specifically, the degradation rate of HC (k = 0.13) was slower than LC (k = 0.30) in muscle, while HC showed the fastest degradation rate in the shoulder and knee joints. In summary, NIR-II imaging could precisely identify the in vivo degradation rate of collagen. Moreover, the degradation rate of collagen was more closely related to the implanted body parts rather than the crosslinking degree of collagen, which was slower in the subcutaneous tissue and muscle compared to the joints in the mouse model.

In Vivo Precision Evaluation of Lymphatic Function by SWIR Luminescence Imaging with PbS Quantum Dots.

Advancements in lymphography technology are essential for comprehensive investigation of the lymphatic system and its function. Here, a shortwave infrared (SWIR) luminescence imaging of lymphatic vessels is proposed in both normal and lymphatic dysfunction in rat models with PbS quantum dots (PbS Qdots). The lymphography with PbS Qdots can clearly and rapidly demonstrate the normal lymphatic morphology in both the tail and hind limb. More importantly, compared to ICG, SWIR luminescence imaging with PbS Qdots can easily identify the dominant lymphatic vessel and node with higher luminescence signal in rats. Moreover, lymphatic pump is identified as segment contracting sections with a size of ≈1 cm in rat by in vivo SWIR lymphograhy, which propose a direct feature for precise evaluation of lymphatic function. Notably, in vivo SWIR luminescence imaging with PbS Qdots also clearly deciphers the in vivo pattern of morphological and function recovery from lymphatic system in rat model. In summary, SWIR luminescence imaging with PbS Qdots can improve the lymphography and thus deepen the understanding of the morphology and structure of the lymphatic system as well as lymphatic function such as lymphatic pump, which will facilitate the diagnosis of lymphatic dysfunction in the future.

Spatio-temporally deciphering peripheral nerve regeneration in vivo after extracellular vesicle therapy under NIR-II fluorescence imaging.

Extracellular vesicles (EVs) show potential as a therapeutic tool for peripheral nerve injury (PNI), promoting neurological regeneration. However, there are limited data on the in vivo spatio-temporal trafficking and biodistribution of EVs. In this study, we introduce a new non-invasive near-infrared fluorescence imaging strategy based on glucose-conjugated quantum dot (QDs-Glu) labeling to target and track EVs in a sciatic nerve injury rat model in real-time. Our results demonstrate that the injected EVs migrated from the uninjured site to the injured site of the nerve, with an increase in fluorescence signals detected from 4 to 7 days post-injection, indicating the release of contents from the EVs with therapeutic effects. Immunofluorescence and behavioral tests revealed that the EV therapy promoted nerve regeneration and functional recovery at 28 days post-injection. We also found a relationship between functional recovery and the NIR-II fluorescence intensity change pattern, providing novel evidence for the therapeutic effects of EV therapy using real-time NIR-II imaging at the live animal level. This approach initiates a new path for monitoring EVs in treating PNI under in vivo NIR-II imaging, enhancing our understanding of the efficacy of EV therapy on peripheral nerve regeneration and its mechanisms.