Regulatory Role of Collagen XI in the Establishment of Mechanical Properties of Tendons and Ligaments in Mice Is Tissue Dependent.

Collagen XI is ubiquitous in tissues such as joint cartilage, cancellous bone, muscles, and tendons and is an important contributor during a crucial part in fibrillogenesis. The COL11A1 gene encodes one of three alpha chains of collagen XI. The present study elucidates the role of collagen XI in the establishment of mechanical properties of tendons and ligaments. We investigated the mechanical response of three tendons and one ligament tissues from wild type and a targeted mouse model null for collagen XI: Achilles tendon (ACH), the flexor digitorum longus tendon (FDL), the supraspinatus tendon (SST), and the anterior cruciate ligament (ACL). Area was substantially lower in Col11a1ΔTen/ΔTen ACH, FDL, and SST. Maximum load and maximum stress were significantly lower in Col11a1ΔTen/ΔTen ACH and FDL. Stiffness was lower in Col11a1ΔTen/ΔTen ACH, FDL, and SST. Modulus was reduced in Col11a1ΔTen/ΔTen FDL and SST (both insertion site and midsubstance). Collagen fiber distributions were more aligned under load in both wild type group and Col11a1ΔTen/ΔTen groups. Results also revealed that the effect of collagen XI knockout on collagen fiber realignment is tendon-dependent and location-dependent (insertion versus midsubstance). In summary, this study clearly shows that the regulatory role of collagen XI on tendon and ligament is tissue specific and that joint hypermobility in type II Stickler's Syndrome may in part be due to suboptimal mechanical response of the soft tissues surrounding joints.

Magnetically induced anisotropic structure in an injectable hydrogel for skeletal muscle regeneration.

Skeletal muscle integrity and its intrinsic aligned architecture are crucial for locomotion, postural support, and respiration functions, impacting overall quality of life. However, volumetric muscle loss (VML) can exceed intrinsic regenerative potential, leading to fibrosis and impairments. Autologous muscle grafting, the current gold standard, is constrained by tissue availability and success rates. Therefore, innovative strategies like cell-based therapies and scaffold-based approaches are needed. Our minimally invasive approach involves a tunable injectable hydrogel capable of achieving an aligned architecture post-injection via a low-intensity static magnetic field (SMF). Our hydrogel formulation uses gellan gum as the backbone polymer, enriched with essential extracellular matrix components such as hyaluronic acid and collagen type I, enhancing bio-functionality. To achieve an aligned architectural biomimicry, collagen type I is coupled with iron oxide magnetic nanoparticles, creating magnetic collagen bundles (MagC) that align within the hydrogel when exposed to a SMF. An extensive study was performed to characterize MagC and assess the hydrogel's stability, mechanical properties, and biological response in vitro and in vivo. The proposed system, fully composed of natural polymers, exhibited mechanical properties similar to human skeletal muscle and demonstrated effective biological performances, supporting its potential as a safe and patient-friendly treatment for VML.

Bioconversion of agriculture by-products with functionally enhanced Streptomyces sp. SCUT-3: Fish skin as a model.

With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion.

Extraction and characterization of valuable compounds from chicken sternal cartilage: Type II collagen and chondroitin sulfate.

Type II collagen (Col II) and chondroitin sulfate (CS) are the main macromolecules in the extracellular matrix. This study investigated the characteristics of Col II and CS obtained from chicken sternal cartilage (CSC) via enzymatic hydrolysis for various treatment times. For Col II and CS, the highest efficiency of enzymatic hydrolysis was achieved after 24 and 6 h of treatment, respectively. The average molecular weights were α1 chain-130 kDa, ß chain-270 kDa for Col II, and 80.27 kDa for CS. Fourier transform infrared spectroscopy revealed that the Col II samples maintained their triple-helical structure and that the predominant type of CS was chondroitin-4-sulfate. Scanning electron microscopy revealed that the Col II and CS samples possessed fibrillar and clustered structures, respectively. This study suggests that collagen and CS obtained from CSC can be used as promising molecules for application in food and pharmaceutical industries.

Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels.

Hydrogels can improve the delivery of mesenchymal stromal cells (MSCs) by providing crucial biophysical cues that mimic the extracellular matrix. The differentiation of MSCs is dependent on biophysical cues like stiffness and viscoelasticity, yet conventional hydrogels cannot be dynamically altered after fabrication and implantation to actively direct differentiation. We developed a composite hydrogel, consisting of type I collagen and phase-shift emulsion, where osteogenic differentiation of MSCs can be non-invasively modulated using ultrasound. When exposed to ultrasound, the emulsion within the hydrogel was non-thermally vaporized into bubbles, which locally compacted and stiffened the collagen matrix surrounding each bubble. Bubble growth and matrix compaction were correlated, with collagen regions proximal (i.e., ≤ ∼60 µm) to the bubble displaying a 2.5-fold increase in Young's modulus compared to distal regions (i.e., > ∼60 µm). The viability and proliferation of MSCs, which were encapsulated within the composite hydrogel, were not impacted by bubble formation. In vitro and in vivo studies revealed encapsulated MSCs exhibited significantly elevated levels of RUNX2 and osteocalcin, markers of osteogenic differentiation, in collagen regions proximal to the bubble compared to distal regions. Additionally, alkaline phosphatase activity and calcium deposition were enhanced adjacent to the bubble. An opposite trend was observed for CD90, a marker of MSC stemness. Following subcutaneous implantation, bubbles persisted in the hydrogels for two weeks, which led to localized collagen alignment and increases in nuclear asymmetry. These results are a significant step toward controlling the 3D differentiation of MSCs in a non-invasive and on-demand manner.

Corneal stromal structure replicating humanized hydrogel patch for sutureless repair of deep anterior-corneal defect.

A critical shortage of donor corneas exists worldwide. Hydrogel patches with a biological architecture and functions that simulate those of native corneas have garnered considerable attention. This study introduces a stromal structure replicating corneal patch (SRCP) composed of a decellularized cornea-templated nanotubular skeleton, recombinant human collagen, and methacrylated gelatin, exhibiting a similar ultrastructure and transmittance (above 80 %) to natural cornea. The SRCP is superior to the conventional recombinant human collagen patch in terms of biomechanical properties and resistance to enzymatic degradation. Additionally, SRCP promotes corneal epithelial and stromal cell migration while preventing the trans-differentiation of stromal cells into myofibroblasts. When applied to an ocular surface (37 °C), SRCP releases methacrylated gelatin, which robustly binds SRCP to the corneal stroma after activation by 405 nm light. Compared to gelatin-based photocurable hydrogel, the SRCP better supports the restoration of normal corneal curvature and withstands deformation under an elevated intraocular pressure (100 mmHg). In an in vivo deep anterior-corneal defect model, SRCP facilitated epithelial healing and vision recovery within 2 weeks, maintained graft structural stability, and inhibited stromal scarring at 4 weeks post-operation. The ideal performance of the SRCP makes it a promising humanized corneal equivalent for sutureless clinical applications.

Antibiotic-eluting scaffolds with responsive dual-release kinetics facilitate bone healing and eliminate S. aureus infection.

Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.

Tailored extracellular matrix-mimetic coating facilitates reendothelialization and tissue healing of cardiac occluders.

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.

Management of Multiple Fractures in a Preadolescent With Osteogenesis Imperfecta Types III-IV.

Osteogenesis imperfecta is an inherited disorder that results in fragile bones that break easily. Gene defects are responsible for the disease. Collagen, a protein that helps strengthen bones, is produced by these genes. The disease can be classified into four types ranging from mild to lethal. Type III or type IV is the most severe forms that survive the neonatal period. In osteogenesis imperfecta strengthening the bone requires correcting the genetic mutations that cause the disorder. Physical rehabilitation, surgical procedures, and clinical management of osteogenesis imperfecta include the use of drugs such as bisphosphonates and recombinant human growth hormone. A nine-year-old male child came to the radiology department with a clinical history of bony deformities of both legs since the age of six years. The child was normal until the age of six years. Then, later, he had a right femur fracture. Surgery was done with a rod inserted in his femur, which was later removed, causing bending of his tibia and fibula. Treatment can improve the quality of life and manage symptoms, but the condition cannot be cured. As part of the treatment, bone-strengthening medications, physiotherapy, and surgery may be required.

Deciphering Collagen Phenotype Dynamics Regulators: Insights from In-Silico Analysis.

Collagen (Col) types I and III are integral components in wound healing and tissue regeneration, influencing tissue development, homeostasis, and related pathologies. Col I and Col III expression changes during different stages of wound healing and understanding the regulation of collagen phenotype determination is crucial for unraveling the complexities of these processes. Transcription factors and microRNAs, directly and indirectly, play a critical role in regulating collagen expression, however, a comprehensive understanding of the factors regulating Col I and III phenotypes remains elusive. This critically analyzed published reports with focuses on various factors regulating the expression of Col I and Col III at the transcriptional and translational levels. We performed bioinformatics analysis with an input of proinflammatory mediators, growth factors, elastases, and matrix metalloproteinases and predicted transcription factors and microRNAs involved in the regulation of collagen expression. Network analysis revealed an interaction between genes, transcription factors, and microRNAs and provided a holistic view of the regulatory landscape governing collagen expression and unveils intricate interconnections. This analysis lays a founda-tional framework for guiding future research and therapeutic interventions to promote extracellular matrix remodeling, wound healing, and tissue regeneration after an injury by modulating collagen expression. In essence, this scientific groundwork offers a comprehensive exploration of the regulatory dynamics in collagen synthesis, serving as a valuable resource for advancing both basic research and clinical interventions in tissue repair.

Intramuscular injection of Bothrops jararaca venom provoked acute kidney injury (AKI): underpinned by impaired renal filtration, Na+ handling, and tissue damage.

Globally, about 2.5 million people are victims of snakebites annually. In Brazil, the most clinically relevant snake is the Bothrops jararaca. The symptoms of envenomation are acute inflammation at the bite site and bleeding disorders. Despite kidney failure being the main cause of death after envenomation, kidney damage is not completely understood, and there are no clinically representative in vivo models. This work aimed to characterize the acute kidney injury (AKI) induced by intramuscular injection (IM) of Bothrops jararaca (Bjc) venom in male Wistar rats. The control group received 0.9% saline solution. Three doses of venom (3.5, 6.0, and 8.0 mg/kg) were administered IM into the posterior region of the right knee. After the injection, the rats were kept in metabolic cages. The following parameters were analyzed after 24 h: the extent of muscle damage and kidney damage (urinary creatinine, proteinuria, plasma creatinine, and renal tissue histology). All rats presented a hemorrhagic lesion at the injection site in a dose-dependent manner. Biochemical parameters indicated kidney damage: plasma creatinine accumulation, decreased glomerular filtration rate, albuminuria and proteinuria, and disturbance in Na+ homeostasis. Histological analyses showed glomerular injury, tissue discontinuity more evident in the cortex and tubular dilatation, and collagen deposition. The decline in renal function and tissue damage indicated the occurrence of AKI. Therefore, a Bjc venom-induced in vivo model of renal injury has been established for future studies.

Spatiotemporally cascade-driven "Lipomicelles" enhance extracellular matrix penetration and remodel intercellular crosstalk in pulmonary fibrosis.

Pulmonary fibrosis (PF) is an inevitable phase of many respiratory diseases with high mortality and limited effective treatments in the clinic. In PF, aberrant extracellular matrix (ECM) deposition is a significant pathological structural alteration that blocks intercellular crosstalk and hinders the deep penetration of therapeutics into lung tissues, reducing the effectiveness of conventional treatment strategies. Herein, a penetrating enhancer (Lipomicelles) composed of thermosensitive liposome shells loaded with collagenase IV and micellar cores containing thioketal bonds encapsulated with curcumin and decorated with cyclic RGDfc, is developed to alleviate PF. Specifically, Lipomicelles exhibit a cascade-responsive pattern to achieve precision delivery of curcumin through thermosensitivity, enhanced ECM penetration, site-specific targeting, and rapid release in injured alveolar epithelial type II cells (CellAEC2s). Subsequently, intercellular crosstalk is remodeled through the curcumin-mediated repair of CellAEC2s, combined with collagenase IV-mediated ECM degradation to inhibit myofibroblasts, ultimately achieving PF reversal. This work provides an innovative approach to enhance ECM penetration of therapeutics before remodeling intercellular crosstalk, addressing multi-phase PF therapy.

Limonene encapsulated alginate/collagen as antibiofilm drug against Acinetobacter baumannii.

This work examined the antibacterial and antibiofilm properties of alginate/collagen nanoparticles containing limonene. The multi-drug resistant (MDR) strains were screened, and the morphological features of the produced nanoparticles were determined utilizing SEM, DLS, and FTIR. Additionally, the encapsulation effectiveness, stability, and drug release were assessed. The levels of OmpA and Bap biofilm genes were assessed using qRT-PCR. At the same time, the antibacterial and cytotoxic activities of the nanoparticles were evaluated using well diffusion and MTT techniques, respectively. LAC nanoparticles measuring 300 ± 9.6 nm in size, 83.64 ± 0.19% encapsulation efficiency, and 60-day stability at 4 °C were synthesized. The biological investigation demonstrated that LAC nanoparticles had potent antibacterial capabilities. This was shown by their ability to significantly decrease the transcription of OmpA and Bap biofilm genes at a statistically significant level of p ≤ 0.05. The nanoparticles exhibited reduced antibiotic resistance compared to free limonene and alginate/collagen. Compared to limonene, LAC nanoparticles exhibited negligible cytotoxicity against HEK-293 at doses ranging from 1.56 to 100 µg/mL (p ≤ 0.01). The findings underscore the potential of LAC nanoparticles as a breakthrough in the fight against highly resistant pathogens. The potent antibacterial effects of LAC nanoparticles versus Acinetobacter baumannii (A. baumannii) MDR strains, considered highly resistant pathogens of significant concern, could inspire new strategies in antibacterial research.

Induced collagen type-I secretion by hepatocytes of the melanoma liver metastasis is associated with a reduction in tumour-infiltrating lymphocytes.

BACKGROUND: Overall patients with melanoma liver metastasis (MLiM) have a dismal prognosis and poor responses to the standard of care treatment. Understanding the role of the tumour microenvironment (TME) is critical for discovering better strategies to overcome intrinsic therapy resistance in MLiM. The aim was to understand the crosstalk signalling pathways between hepatocytes and metastatic melanoma cells in the TME of MLiM. METHODS: Hepatocytes and melanoma tumour cells of MLiM were assessed using transcriptomic NanoString GeoMx digital spatial profiling (NGDSP) assay. Functional assays were performed using normal hepatocytes and MLiM-derived cell lines. Validation was performed using multiplex immunofluorescence. RESULTS: In NGDSP analysis adjacent normal hepatocytes (ANH) had higher CXCR4 and COL1A1/2 levels than distant normal hepatocytes (DNH), while melanoma cells had higher TNF-α levels. In vitro, MLiM cell lines released TNF-α which upregulated CXCR4 and CXCL12 levels in ANH. CXCL12 activated CXCR4, which triggered AKT and NFκB signalling pathways. Consequently, AKT signalling induced the upregulation of collagen type I. MLiM were significantly encircled by a shield of collagen, whereas other liver metastases showed reduced levels of collagen. Of all the liver metastasis analyzed, the presence of collagen in melanoma liver metastasis was associated with a reduction in tumour-infiltrating lymphocytes. CONCLUSIONS: MLiM modified ANH to increase collagen production and created a physical barrier. The collagen barrier was associated with a reduction of immune cell infiltration which could potentially deter MLiM immune surveillance and treatment responses. HIGHLIGHTS: Spatial analyses of melanoma liver metastasis show that adjacent normal hepatocytes have increased collagen-type I levels. Melanoma liver metastases tumour cells secrete enhanced levels of TNF-α to stimulate CXCR4/CXCL12 upregulation in adjacent normal hepatocytes. Activation of CXCR4 promotes AKT and NF-κB signalling pathways to promote collagen-type I secretion in adjacent normal hepatocytes. Elevated collagen levels were associated with reduced tumour-infiltrating lymphocytes.

Relationship between bone union and degree of bone marrow fibrosis at resection margins of advanced mandibular ORN.

BACKGROUND: The pathological evaluation of cancellous bone at resection margins of mandibular osteoradionecrosis (ORN) has not been well elucidated. Here, we developed a unique classification system for evaluating the degree of bone marrow fibrosis, one of most common pathological features, in patients with mandibular ORN, based on which we investigated its relationship with treatment outcome. METHODS: This study included 15 patients who underwent mandibulectomy and free fibula osteocutaneous flap reconstruction. The extent of mandibulectomy was determined, with safety margins of approximately 10 mm from the apparent osteolytic areas on preoperative computed tomography image. Special staining was performed on thin sections from center of the osteolytic areas (medial area) and bilateral resection margins, and the degree of bone marrow fibrosis was evaluated and investigated its relationship with presence of bone union as a treatment outcome. RESULTS: The degree of bone marrow fibrosis of medial area was significantly higher than those of resection margins. Although most resection margins had collagen fibers which indicate severe fibrosis, all transferred fibula flaps achieved bone union. CONCLUSION: When mandibulectomy is performed with safety margins of approximately 10 mm from the apparent osteolytic areas, all transferred fibula flaps achieved bone union regardless of the degree of bone marrow fibrosis at resection margin. In other words, the association between severe bone marrow fibrosis at resection margins and treatment outcome was not seen. CLINICAL RELEVANCE: Setting safety margins of approximately 10 mm may achieve bone union, but further study is needed.

Facial Rejuvenation Strategy in Asian Women with Autologous Fat Transplantation.

OBJECTIVE: To explore the clinical strategy of autologous fat transplantation in facial rejuvenation. METHODS: From September 2016 to May 2023, 2715 female patients with facial filling by autologous fat were retrospectively analysed. After treatment, they were followed up for 3-6 months to summarize the relationship between aesthetic design and treatment outcomes. RESULTS: In total, 2306 patients were followed up and completed the questionnaires of satisfactory. Most patients (97%, 2237 cases) achieved satisfactory results after one operation, and about 3% (69 cases) achieved satisfactory results after secondary filling. CONCLUSION: Autologous fat granule transplantation in the treatment of facial rejuvenation can achieve an excellent therapeutic outcome. Customized design according to the different lineaments, age, and other factors, and extensive use of various treatment methods can achieve better results. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The influence of triiodothyronine on the immune response and extracellular matrix remodeling during zebrafish heart regeneration.

Damage to the human heart is an irreparable process that results in a permanent impairment in cardiac function. There are, however, a number of vertebrate species including zebrafish (Danio rerio) that can regenerate their hearts following significant injury. In contrast to these regenerative species, mammals are known to have high levels of thyroid hormones, which has been proposed to play a role in this difference in regenerative capacity. However, the mechanisms through which thyroid hormones effect heart regeneration are not fully understood. Here, zebrafish were exposed to exogenous triiodothyronine (T3) for two weeks and then their hearts were damaged through cryoinjury to investigate the effect of thyroid hormones on ECM remodeling and the components of the immune response during heart regeneration. Additionally, cardiac fibroblasts derived from trout, another species of fish known to display cardiac regenerative capacity, were exposed to T3in vitro to analyze any direct effects of T3 on collagen deposition. It was found that cryoinjury induction results in an increase in myocardial stiffness, but this response was muted in T3 exposed zebrafish. The measurement of relevant marker gene transcripts suggests that T3 exposure reduces the recruitment of macrophages to the damaged zebrafish heart immediately following injury but had no effect on the regulation of collagen deposition by cultured trout fibroblasts. These results suggest that T3 effects both the immune response and ECM remodeling in zebrafish following cardiac injury.

Family-based whole-exome sequencing implicates a variant in lysyl oxidase like 4 in atypical femur fractures.

Atypical femur fractures (AFFs) are rare adverse events associated with bisphosphonate use, having unclear pathophysiology. AFFs also cluster in families and have occurred in patients with monogenetic bone diseases sometimes without bisphosphonate use, suggesting an underlying genetic susceptibility. Our aim was to identify a genetic cause for AFF in a Caucasian family with seven members affected by osteoporosis, including three siblings with bisphosphonate-associated AFFs. Using whole-exome sequencing, we identified a rare pathogenic variant c.G1063A (p.Gly355Ser) in lysyl oxidase like 4 (LOXL4) among 64 heterozygous rare, protein-altering variants shared by the three siblings with AFFs. The same variant was also found in a fourth sibling with a low-trauma femur fracture above the knee, not fulfilling all the ASBMR criteria of AFF and in one of 73 unrelated European AFF patients. LOXL4 is involved in collagen cross-linking and may be relevant for microcrack formation and bone repair mechanisms. Preliminary functional analysis showed that skin fibroblast-derived osteoblasts from the unrelated patient with the LOXL4 variant expressed less collagen type I and elastin, while osteogenic differentiation and mineralization were enhanced compared with two controls. In conclusion, this LOXL4 variant may underlie AFF susceptibility possibly due to abnormal collagen metabolism leading to increased formation of microdamage or compromised healing of microcracks in the femur.

Atypical femur fractures (AFFs) are rare fractures of the upper leg that can occur in people using bisphosphonates for osteoporosis. Genetic factors may play a role. We studied a family with seven members affected by osteoporosis, including three siblings who developed AFFs after using bisphosphonates. In this family, a rare variant in the LOXL4 gene was identified as a potential cause for AFFs. This variant was also present in another sibling who had a different type of upper leg fracture, and in one of 73 unrelated European patients with AFFs. LOXL4 is involved in collagen cross-linking, a crucial bone formation process. The variant may impair collagen metabolism, leading to increased microdamage or compromised bone healing, which could increase the risk of AFFs.

Leather-Based Shoe Soles for Real-Time Gait Recognition and Automatic Remote Assistance Using Machine Learning.

Real-time monitoring of gait characteristics is crucial for applications in health monitoring, patient rehabilitation feedback, and telemedicine. However, the effective and stable acquisition and automatic analysis of gait information remain significant challenges. In this study, we present a flexible sensor based on a carbon nanotube/graphene composite conductive leather (CGL), which uses collagen fiber with a three-dimensional network structure as the flexible substrate. The CGL-based sensor demonstrates a high dynamic range, with notable pressure responses ranging from 0.6 to 14.5 kPa and high sensitivity (S = 0.2465 kPa-1). We further developed a device incorporating the CGL-based sensor to collect foot characteristic signals from human motion and designed smart sports shoes to facilitate effective human-computer interaction. Machine learning was employed to collect and process gait characteristic information in various states, including standing, sitting, walking, and falling. For real-time monitoring of falls, we optimized the K-Nearest Time Series Classifier (KNTC) algorithm, achieving an accuracy of 0.99 and a prediction time of only 13 ms, which highlights the system's excellent intelligent response capabilities. The system maintained a gait recognition accuracy of 90% across diverse populations, with low false-positive (3.3%) and false-negative (3.3%) rates. This work demonstrates stable gait recognition capabilities and provides valuable methods and insights for plantar behavior monitoring and data analysis, contributing to the development of advanced real-time gait monitoring systems.

Energy-Based Skin Rejuvenation: A Review of Mechanisms and Thermal Effects.

BACKGROUND: Energy-based photoelectric and ultrasonic devices are essential for skin rejuvenation and resurfacing in the field of plastic surgery and dermatology. Both functionality and appearance are impacted by factors that cause skin to age, and various energy types have variable skin penetration depths and modes of transmission. AIM: The objective is to advise safe and efficient antiaging treatment while precisely and sensitively controlling and assessing the extent of thermal damage to tissues caused by different kinds of energy-based devices. METHODS: A literature search was conducted on PubMed to review the mechanisms of action and thermal effects of photoelectric and ultrasonic devices in skin remodeling applications. RESULTS: This paper reviews the thermal effects of energy-based devices in skin resurfacing applications, including the tissue level and molecular biochemical level. It seeks to summarize the distribution form, depth of action, and influencing factors of thermal effects in combination with the mechanisms of action of various types of devices. CONCLUSION: Accurate control of thermal damage is crucial for safe and effective skin remodeling treatments. Thorough investigation of molecular biochemical indicators and signaling pathways is needed for real-time monitoring and prevention of severe thermal injury. Ongoing research and technological advancements will improve the accuracy and control of thermal damage during treatments.