Exploring Cr and molten salt interfacial interactions for molten salt applications.

Molten salts play an important role in various energy-related applications such as high-temperature heat transfer fluids and reaction media. However, the extreme molten salt environment causes the degradation of materials, raising safety and sustainability challenges. A fundamental understanding of material-molten salt interfacial evolution is needed. This work studies the transformation of metallic Cr in molten 50/50 mol% KCl-MgCl2via multi-modal in situ synchrotron X-ray nano-tomography, diffraction and spectroscopy combined with density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. Notably, in addition to the dissolution of Cr in the molten salt to form porous structures, a δ-A15 Cr phase was found to gradually form as a result of the metal-salt interaction. This phase change of Cr is associated with a change in the coordination environment of Cr at the interface. DFT and AIMD simulations provide a basis for understanding the enhanced stability of δ-A15 Cr vs. bcc Cr, by revealing their competitive phase thermodynamics at elevated temperatures and probing the interfacial behavior of the molten salt at relevant facets. This study provides critical insights into the morphological and chemical evolution of metal-molten salt interfaces. The combination of multimodal synchrotron analysis and atomic simulation also offers an opportunity to explore a broader range of systems critical to energy applications.

Supercharge end-to-side nerve transfer from anterior interosseous nerve to augment intrinsic recovery in high ulnar nerve injuries of varying magnitudes.

BACKGROUND: High ulnar nerve injuries result in intrinsic muscle weakness and are inconvenient for patients. Moreover, conventional surgical techniques often fail to achieve satisfactory motor recovery. A potential reconstructive solution in the form of the supercharge end-to-side (SETS) anterior interosseous nerve (AIN) transfer method has emerged. Therefore, this study aims to compare surgical outcomes of patients with transected and in-continuity high ulnar nerve lesions following SETS AIN transfer. METHODS: Between June 2015 and May 2023, patients with high ulnar palsy in the form of transection injuries or lesion-in-continuity were recruited. The assessment encompassed several objective results, including grip strength, key pinch strength, compound muscle action potential, sensory nerve action potential, and two-point discrimination tests. The muscle power of finger abduction and adduction was also recorded. Additionally, subjective questionnaires were utilized to collect data on patient-reported outcomes. Overall, the patients were followed up for up to 2 years. RESULTS: Patients with transected high ulnar nerve lesions exhibited worse baseline performance than those with lesion-in-continuity, including motor and sensory functions. However, they experienced greater motor improvement but less sensory recovery, resulting in comparable final motor outcomes in both groups. In contrast, the transection group showed worse sensory outcomes. CONCLUSIONS: Our findings suggest that SETS AIN transfer benefits patients with high ulnar nerve palsy, regardless of the lesion type. Nonetheless, improvements may be more pronounced in patients with transected lesions.

L-Glutamine Substantially Improves 5-Fluorouracil-Induced Intestinal Mucositis by Modulating Gut Microbiota and Maintaining the Integrity of the Gut Barrier in Mice.

SCOPE: This study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS AND RESULTS: Over twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg-1) or high (2 mg kg-1) doses of L-Glutamine daily, with 5-FU (50 mg kg-1) administered between days six and nine. Mice receiving only 5-FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short-chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway, modulating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa. CONCLUSIONS: These findings underscore glutamine's potential in preventing 5-FU-induced mucositis by modulating gut microbiota and inflammation pathways.

Evolution and Diversity of Medial Sural Artery Perforator Flap for Hand Reconstruction.

The free medial sural artery perforator (MSAP) flap is a recently popularized flap. It has evolved from a composite myocutaneous flap to a pedicled perforator flap for lower limb reconstruction. It is also a versatile free perforator flap for extremity and head and neck reconstruction. The diversity of the flap designs with options for harvest of non-vascularized grafts enhances the versatility for hand and upper limb reconstruction. The adjunctive use of endoscopy and indocyanine green fluorescence imaging studies can assist and demystify the flap anatomy. The authors present their experience using free MSAP flaps for complex mutilated hand and upper extremity reconstruction.

Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells by Hydrogel Encapsulation.

Mesenchymal stromal cells (MSCs) showcase remarkable immunoregulatory capabilities in vitro, positioning them as promising candidates for cellular therapeutics. However, the process of administering MSCs and the dynamic in vivo environment may impact the cell-cell and cell-matrix interactions of MSCs, consequently influencing their survival, engraftment, and their immunomodulatory efficacy. Addressing these concerns, hydrogel encapsulation emerges as a promising solution to enhance the therapeutic effectiveness of MSCs in vivo. Hydrogel, a highly flexible crosslinked hydrophilic polymer with a substantial water content, serves as a versatile platform for MSC encapsulation. Demonstrating improved engraftment and heightened immunomodulatory functions in vivo, MSCs encapsulated by hydrogel are at the forefront of advancing therapeutic outcomes. This review delves into current advancements in the field, with a focus on tuning various hydrogel parameters to elucidate mechanistic insights and elevate functional outcomes. Explored parameters encompass hydrogel composition, involving monomer type, functional modification, and co-encapsulation, along with biomechanical and physical properties like stiffness, viscoelasticity, topology, and porosity. The impact of these parameters on MSC behaviors and immunomodulatory functions is examined. Additionally, we discuss potential future research directions, aiming to kindle sustained interest in the exploration of hydrogel-encapsulated MSCs in the realm of immunomodulation.

Exploring the Role of Free Tissue Transfers in the Preservation of Bone Length and Knee Joint Function after Lower Limb Trauma: A Retrospective Analysis.

Lower limb trauma often results in mangled extremities, and in some cases, complete amputation may be necessary. However, limiting the extent of amputation and preserving the major knee joint are crucial to enhance mobility and overall functionality. By providing painless soft tissue coverage on the stump, early prosthesis use and the initiation of physiotherapy become more feasible. Soft tissue transfers hold the potential to benefit patients in two essential aspects: first, resolving soft tissue deficiencies without causing bone shortening, and second, preparing the stump to enhance overall functionality. A retrospective study conducted at Chang Gung Memorial Hospital (2009-2016) focused on lower limb amputation patients who underwent soft tissue transfers at different time periods compared to those without stump reconstruction. Out of the 2391 cases of lower limb injuries treated operatively, 117 amputations were performed in 110 patients (44 above the knee and 73 below the knee). Among them, 12 patients received soft tissue transfers for limb salvage and soft tissue deficiency after amputations. It was observed that patients in this group were typically younger, predominantly female, had longer hospital stays, and underwent a greater number of surgical procedures (p < 0.05). Through the use of soft tissue transfers, successfully preserved tibial bone length and functional knee joint in selected patients was achieved. This approach effectively resolved soft tissue deficiencies following lower limb amputations, optimizing physiotherapy and facilitating functional rehabilitation.

Predicting Union, Osteomyelitis, and Amputation Outcomes of Gustilo IIIC Open Tibial Fractures: A Retrospective Study.

OBJECTIVE: Open tibial fractures are frequently encountered in high-energy traumas and can result in significant complications such as nonunion, osteomyelitis, and even amputation. Among open tibial fractures, Gustilo type IIIC cases are particularly challenging due to the concomitant occurrence of neurovascular injuries and soft tissue defects. This study aimed to assess factors that affect union time and complications in Gustilo IIIC tibial fractures. METHODS: Patients who presented at our center with IIIC open tibial fractures from January 2000 to October 2020 were eligible for this retrospective analysis. Patient demographics, fracture characteristics, and the timing, number, and type of surgical intervention were documented. Outcomes of interest included union time, occurrence of osteomyelitis, and amputation. We performed univariate analyses including chi-squared test, Fischer's exact test, analysis of variance, and Kruskal-Wallis test based on the normality of the data and multivariate analyses including Cox proportional hazards model and logistic regression analyses. RESULTS: Fifty-eight patients were enrolled and grouped by fracture healing time; eight had timely union (13.8%); 27 had late union (46.6%); eight had delayed union (13.8%); three had nonunion (5.2%); and 12 underwent amputation (20.7%). Nine fractures (15.5%) were complicated by osteomyelitis. Union time was prolonged in cases of triple arterial injury, distal third fractures, multiple trauma with injury severity score (ISS) ≥ 16 points, and increased bone defect length. Additionally, a bone gap >50 mm, diabetes mellitus, low body mass index, and triple arterial injury in the lower leg were significant risk factors for amputation. A time from injury to definitive soft tissue coverage of more than 22 days was the major risk factor for osteomyelitis. A scoring system to predict union time was devised and the predicted probability of union within 2 years was stratified based on this score. CONCLUSION: IIIC tibial fractures involving the distal third of the tibia, fractures with bone defects, triple arterial injury, and multiple trauma with ISS ≥16 points demonstrated delayed union, and an effective prediction system for union time was introduced in this study. Early soft tissue coverage can reduce the risk of osteomyelitis. Finally, diabetes and severe bone and soft tissue defects pose a higher risk of amputation.

Lambda Repair: A Novel Repair Technique for Chronic Boutonnière Deformity.

SUMMARY: Correction of a boutonnière deformity is one of the most demanding challenges in hand surgery. Surgical interventions are usually considered when functional use of the finger cannot be obtained after intense hand therapy. The authors introduce their newly described lambda (λ) repair, which is an easy-to-learn, straightforward surgical technique. The method involves an end-to-side tenorrhaphy of the lateral bands, resembling the Greek λ. Patients who underwent a lambda repair were retrospectively evaluated with preoperative and postoperative measurements of proximal interphalangeal (PIP) joint movement. Four patients (two male, two female; median age, 35.5 years) with a median follow-up period of 9.1 months were included. Three patients underwent lambda repairs for isolated boutonnière deformities, and one patient received a vascularized free toe transfer combined with a lambda repair. The preoperative average PIP joint extension lag or deficit was 28.75 degrees and could be reduced to 15 degrees. Preoperative average PIP joint active flexion was 60 degrees, which was improved to 88.75 degrees. No complications were observed. The lambda repair is a new tool in the reconstruction of boutonnière deformity, further expanding the armamentarium of hand surgeons.

Deep learning for the identification of ridge deficiency around dental implants.

OBJECTIVES: This study aimed to use a deep learning (DL) approach for the automatic identification of the ridge deficiency around dental implants based on an image slice from cone-beam computerized tomography (CBCT). MATERIALS AND METHODS: Single slices crossing the central long-axis of 630 mandibular and 845 maxillary virtually placed implants (4-5 mm diameter, 10 mm length) in 412 patients were used. The ridges were classified based on the intraoral bone-implant support and sinus floor location. The slices were either preprocessed by alveolar ridge homogenizing prior to DL (preprocessed) or left unpreprocessed. A convolutional neural network with ResNet-50 architecture was employed for DL. RESULTS: The model achieved an accuracy of >98.5% on the unpreprocessed image slices and was found to be superior to the accuracy observed on the preprocessed slices. On the mandible, model accuracy was 98.91 ± 1.45%, and F1 score, a measure of a model's accuracy in binary classification tasks, was lowest (97.30%) on the ridge with a combined horizontal-vertical defect. On the maxilla, model accuracy was 98.82 ± 1.11%, and the ridge presenting an implant collar-sinus floor distance of 5-10 mm with a dehiscence defect had the lowest F1 score (95.86%). To achieve >90% model accuracy, ≥441 mandibular slices or ≥592 maxillary slices were required. CONCLUSIONS: The ridge deficiency around dental implants can be identified using DL from CBCT image slices without the need for preprocessed homogenization. The model will be further strengthened by implementing more clinical expertise in dental implant treatment planning and incorporating multiple slices to classify 3-dimensional implant-ridge relationships.

Perfusion Dynamics during Secondary Flap Debulking with Liposuction.

BACKGROUND: Lower extremity trauma often necessitates reconstruction with flap transfer. One of the reconstructive goals is a thin soft tissue coverage with appropriate contour. Therefore, a secondary debulking of the flap is usually performed. METHODS: Debulking through conventional lipectomy is compared with liposuction followed by excision of the defatted flap excess. Demographic data, surgical details, and postoperative outcomes are compared and analyzed. The perfusion dynamics of the flaps undergoing liposuction debulking are studied by means of perioperative indocyanine green fluorescence angiography, as well as postoperative laser Doppler imaging. RESULTS: Patients undergoing lipectomy (n = 69; 57.5%) or liposuction (n = 51; 42.5%) debulking had a similar rate of postoperative complications. Partial necrosis was observed in 7.2% (lipectomy) versus 7.8% (liposuction) of flaps. Fluorescence angiography showed a substantial decrease in flap perfusion following the infiltration with an epinephrine-containing tumescent solution (74.3% ± 8.2% prior to infiltration versus 16.8% ± 7.1% after infiltration; p < 0.001), resulting in a dark flap appearance. Laser Doppler imaging confirmed the hypoperfusion on postoperative day 1. CONCLUSION: Secondary debulking of a lower extremity flap can be safely and efficiently performed through liposuction combined with peripheral excision of the defatted flap in a single stage. Perfusion studies may show a misleading hypoperfusion of the defatted flap, which does not accurately predict subsequent necrosis or complications.

Stack versus Te technique for central slip reconstruction during vascularized toe proximal interphalangeal joint transfer.

BACKGROUND: Significant extension deficit is a common problem after a vascularized toe proximal interphalangeal joint transfer. One of the main causes related to extensor lag is central slip deficiency of the donor toes. In our clinical practice, we performed both the Stack and Te technique to reconstruct central slip function during a joint transfer. The aim of this study was to compare the long-term outcomes of vascularized joint transfers between these two techniques. PATIENTS AND METHODS: From May 2009 to October 2021, 38 digits in 36 patients (28 men and 8 women) underwent free vascularized toe joint transfer requiring central slip reconstruction. Eight and 30 digits were reconstructed with the Stack and Te technique, respectively. RESULTS: The median length of follow-up was 19 months (range, 5 to 78 months). The overall median extension lag was 20±20 degrees and the flexion was 80±20 degrees. There were no significant differences in extension lag (25±29 vs. 20±15 degrees, p = 0.281), flexion (75±10 vs. 85±20 degrees, p = 0.13), and range of motion (53±23 vs. 63±15 degrees, p = 0.076) of the joints between the Stack and Te techniques after the transfers. CONCLUSIONS: From the limited number of cases, both the Stack and Te techniques provided similar outcomes in correcting extension lag in vascularized joint transfers. The Te technique is a simplified and effective method for central slip reconstruction, while caution is advised when using the Stack technique due to potential complications.Clinical question/level of evidence: Therapeutic, IV.

Vascularized Toe Proximal Interphalangeal Joint Transfer in Posttraumatic Fingers: Analysis of Prognostic Factors for Suboptimal Outcomes.

Background: Posttraumatic finger osteoarthritis of the proximal interphalangeal joint (PIPJ) is a difficult problem. Over the past decade, we have reported several methods for improving the outcomes of vascularized toe joint transfer (VJT). In this study, we focused on determining poor prognostic factors which lead to a suboptimal outcome. Methods: A consecutive series of patients with posttraumatic osteoarthritis of the PIPJ who received VJT between January 2008 and January 2021 were enrolled in this study. The senior surgeon (Y.-T.L.) performed the surgery in all cases. In this retrospective study, we reexamine the initial trauma-related soft tissue and bony structure injuries of the recipient finger, to assess the baseline tissue quality before VJT. The injuries were classified into five major categories according to their anatomic region. The functional outcome parameters (including range of motion, percentage of use, and extensor lag of the transferred PIPJ) were collected. Univariate and multivariate linear regression analyses were performed using the generalized estimated equation model to identify the correlation between the injury category involved and functional outcome. Results: A total of 59 digits were enrolled. Our results revealed that the fingers with previous vascular injury that received revascularization procedures had relatively suboptimal functional outcomes. These fingers had a significantly lower percentage of use both before (ß = -0.222, P = 0.006) and after (ß = -0.177, P = 0.006) receiving secondary procedures to improve functional outcome. Conclusions: Patients with prior revascularization surgery were associated with a poor functional outcome after VJT.

In situ synchrotron X-ray total scattering measurements and analysis of colloidal CsPbX3 nanocrystals during flow synthesis.

In situ X-ray scattering measurements of CsPbX3 (X = Cl, Br, I) nanocrystal formation and halide exchange at NSLS-II beamlines were performed in an automated flow reactor. Total scattering measurements were performed at the 28-ID-2 (XPD) beamline and small-angle X-ray scattering at the 16-ID (LiX) beamline. Nanocrystal structural parameters of interest, including size, size distribution and atomic structure, were extracted from modeling the total scattering data. The results highlight the potential of these beamlines and the measurement protocols described in this study for studying dynamic processes of colloidal nanocrystal synthesis in solution with timescales on the order of seconds.

Automated Age-Related Macular Degeneration Detector on Optical Coherence Tomography Images Using Slice-Sum Local Binary Patterns and Support Vector Machine.

Artificial intelligence has revolutionised smart medicine, resulting in enhanced medical care. This study presents an automated detector chip for age-related macular degeneration (AMD) using a support vector machine (SVM) and three-dimensional (3D) optical coherence tomography (OCT) volume. The aim is to assist ophthalmologists by reducing the time-consuming AMD medical examination. Using the property of 3D OCT volume, a modified feature vector connected method called slice-sum is proposed, reducing computational complexity while maintaining high detection accuracy. Compared to previous methods, this method significantly reduces computational complexity by at least a hundredfold. Image adjustment and noise removal steps are excluded for classification accuracy, and the feature extraction algorithm of local binary patterns is determined based on hardware consumption considerations. Through optimisation of the feature vector connection method after feature extraction, the computational complexity of SVM detection is significantly reduced, making it applicable to similar 3D datasets. Additionally, the design supports model replacement, allowing users to train and update classification models as needed. Using TSMC 40 nm CMOS technology, the proposed detector achieves a core area of 0.12 mm2 while demonstrating a classification throughput of 8.87 decisions/s at a maximum operating frequency of 454.54 MHz. The detector achieves a final testing classification accuracy of 92.31%.

Preliminary Prospective Preoperative and Postoperative Evaluation of Median Nerve Stiffness by Using Sonoelastography.

ABSTRACT: Carpal tunnel syndrome is the most common peripheral nerve entrapment syndrome. No previous studies have compared preoperative and follow-up sonoelastography results or investigated the correlation of median nerve stiffness with the subjective/objective outcomes. Therefore, the aim of this study was to compare the preoperative and postoperative elastography after carpal tunnel release and find the correlation with associated subjective/objective outcomes.From May 2017 to March 2020, 32 patients (6 males, 26 females; 34 hands) with carpal tunnel syndrome were enrolled in this prospective study. Demographic data, QuickDASH score (Chinese version), Boston Carpal Tunnel Questionnaire (Chinese version), nerve conduction velocity/electromyography, and median nerve stiffness by sonoelastography were recorded.Comparisons of preoperative and average sonoelastography findings 1.5 years postoperatively showed a significant decrease in stiffness presented by velocity (Vs) (preoperative Vs, 4.63 ± 1.27 m/s, vs postoperative Vs, 3.39 ± 0.59 m/s; P < 0.001). Changes in subjective functional outcomes also showed the same significant trend. Based on the neurophysiologic study, the improvement of nerve conduction study and elastography have the significant correlation.The same trend of preoperative and postoperative changes in median nerve stiffness and subjective questionnaires/objective neurophysiologic studies may imply that sonoelastography can be used to assess the response to surgery in patients with carpal tunnel syndrome.

Neurectomy of the Nerve of Henle Associated with Periarterial Sympathectomy for Management of Intractable Raynaud's Phenomenon.

BACKGROUND: In periarterial sympathectomy for intractable Raynaud's phenomenon, the extent of adventitiectomy as well as postoperative outcomes and hand perfusion assessment tools remain debatable. We evaluated the outcome of neurectomy of the nerve of Henle combined with ulnar tunnel release and periarterial adventitiectomy in the treatment of refractory Raynaud's phenomenon using objective measurements and patient-reported outcomes. METHODS: Nineteen patients with 20 affected hands were prospectively enrolled and underwent the proposed procedures from 2015 to 2021. Relevant data, including Michigan Hand Outcomes Questionnaire and 36-Item Short Form health questionnaire scores, were documented for analysis during a 3-year follow-up. RESULTS: The average ingress value of the three measured fingers (index, long, and ring) on indocyanine green angiography increased after surgery (p=0.02). The median number of ulcers decreased (p<0.001) and the median digital skin temperature increased (p<0.001). Questionnaire scores showed improvement in physical aspects, such as overall hand function (p≤0.001), activities of daily living (p=0.001), work performance (p=0.02), pain (p<0.001), physical function (p=0.053), and general health (p=0.048), as well as mental aspects, such as patient satisfaction (p<0.001) and mental health (p=0.001). The average indocyanine green ingress value of the three measured fingers significantly correlated with the patient-reported outcomes, including overall hand function (r=0.46, p=0.04), work performance (r=0.68, p=0.001), physical function (r=0.51, p=0.02), and patient satisfaction (r=0.35, p=0.03). CONCLUSIONS: The proposed surgical procedures provided satisfactory outcomes, both subjectively and objectively, over a follow-up period of up to 3 years. Indocyanine green angiography may provide rapid and quantitative measurements for perioperative hand perfusion assessment.

Optical Microphone-Based Speech Reconstruction System With Deep Learning for Individuals With Hearing Loss.

OBJECTIVE: Although many speech enhancement (SE) algorithms have been proposed to promote speech perception in hearing-impaired patients, the conventional SE approaches that perform well under quiet and/or stationary noises fail under nonstationary noises and/or when the speaker is at a considerable distance. Therefore, the objective of this study is to overcome the limitations of the conventional speech enhancement approaches. METHOD: This study proposes a speaker-closed deep learning-based SE method together with an optical microphone to acquire and enhance the speech of a target speaker. RESULTS: The objective evaluation scores achieved by the proposed method outperformed the baseline methods by a margin of 0.21-0.27 and 0.34-0.64 in speech quality (HASQI) and speech comprehension/intelligibility (HASPI), respectively, for seven typical hearing loss types. CONCLUSION: The results suggest that the proposed method can enhance speech perception by cutting off noise from speech signals and mitigating interference caused by distance. SIGNIFICANCE: The results of this study show a potential way that can help improve the listening experience in enhancing speech quality and speech comprehension/intelligibility for hearing-impaired people.

Incidence and Risk Factors for Extremity Osteoradionecrosis after Limb-Sparing Surgery and Adjuvant Radiotherapy.

Osteoradionecrosis (ORN) is a major complication after radiotherapy. Most studies on ORN have focused on patients with mandibular lesions, with few studies including patients with extremity soft tissue sarcoma (STS). We included 198 patients with extremity STS who underwent limb-sparing surgery and adjuvant radiotherapy between 2004 and 2017. The incidence rate of extremity ORN was 3.5% (7/198), with most lesions (6/7) located in the lower extremities. The mean follow-up time was 62 months. Clinical presentations included chronic ulcers, soft tissue necrosis, sinus discharge, bone nonunion, and pathological fractures. Compared with the non-ORN group, the ORN group had a significantly higher total radiation dose (68 Gy vs. 64 Gy, p = 0.048) and greater use of intraoperative periosteal stripping (p = 0.008). Repeat surgeries and subsequent soft tissue reconstruction or limb amputation were performed as treatments. The risk and management of ORN in patients with extremity STS was ignored previously. Because the disease is complex and affects both clinicians and patients, careful surveillance should be undertaken.

Toward transplantation tolerance with adipose tissue-derived therapeutics.

Solid organ and composite tissue allotransplanation have been widely applied to treat end-stage organ failure and massive tissue defects, respectively. Currently there are a lot of research endeavors focusing on induction of transplantation tolerance, to relieve the burden derived from long-term immunosuppressant uptake. The mesenchymal stromal cells (MSCs) have been demonstrated with potent immunomodulatory capacities and applied as promising cellular therapeutics to promote allograft survival and induce tolerance. As a rich source of adult MSCs, adipose tissue provides additional advantages of easy accessibility and good safety profile. In recent years, the stromal vascular fraction (SVF) isolated from adipose tissues following enzymatic or mechanical processing without in vitro culture and expansion has demonstrated immunomodulatory and proangiogenic properties. Furthermore, the secretome of AD-MSCs has been utilized in transplantation field as a potential "cell-free" therapeutics. This article reviews recent studies that employ these adipose-derived therapeutics, including AD-MSCs, SVF, and secretome, in various aspects of organ and tissue allotransplantation. Most reports validate their efficacies in prolonging allograft survival. Specifically, the SVF and secretome have performed well for graft preservation and pretreatment, potentially through their proangiogenic and antioxidative capacities. In contrast, AD-MSCs were suitable for peri-transplantation immunosuppression. The proper combination of AD-MSCs, lymphodepletion and conventional immunosuppressants could consistently induce donor-specific tolerance to vascularized composite allotransplants (VCA). For each type of transplantation, optimizing the choice of therapeutics, timing, dose, and frequency of administration may be required. Future progress in the application of adipose-derived therapeutics to induce transplantation tolerance will be further benefited by continued research into their mechanisms of action and the development of standardized protocols for isolation methodologies, cell culture, and efficacy evaluation.

Donor derived hematopoietic stem cell niche transplantation facilitates mixed chimerism mediated donor specific tolerance.

Compelling experimental evidence confirms that the robustness and longevity of mixed chimerism (MC) relies on the persistence and availability of donor-derived hematopoietic stem cell (HSC) niches in recipients. Based on our prior work in rodent vascularized composite allotransplantation (VCA) models, we hypothesize that the vascularized bone components in VCA bearing donor HSC niches, thus may provide a unique biologic opportunity to facilitate stable MC and transplant tolerance. In this study, by utilizing a series of rodent VCA models we demonstrated that donor HSC niches in the vascularized bone facilitate persistent multilineage hematopoietic chimerism in transplant recipients and promote donor-specific tolerance without harsh myeloablation. In addition, the transplanted donor HSC niches in VCA facilitated the donor HSC niches seeding to the recipient bone marrow compartment and contributed to the maintenance and homeostasis of stable MC. Moreover, this study provided evidences that chimeric thymus plays a role in MC-mediated transplant tolerance through a mechanism of thymic central deletion. Mechanistic insights from our study could lead to the use of vascularized donor bone with pre-engrafted HSC niches as a safe, complementary strategy to induce robust and stable MC-mediated tolerance in VCA or solid organ transplantation recipients.