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The basic helix-loop-helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members1. Here we investigate how chromatinized E-boxes are engaged by two structurally diverse bHLH proteins: the proto-oncogene MYC-MAX and the circadian transcription factor CLOCK-BMAL1 (refs. 2,3). Both transcription factors bind to E-boxes preferentially near the nucleosomal entry-exit sites. Structural studies with engineered or native nucleosome sequences show that MYC-MAX or CLOCK-BMAL1 triggers the release of DNA from histones to gain access. Atop the H2A-H2B acidic patch4, the CLOCK-BMAL1 Per-Arnt-Sim (PAS) dimerization domains engage the histone octamer disc. Binding of tandem E-boxes5-7 at endogenous DNA sequences occurs through direct interactions between two CLOCK-BMAL1 protomers and histones and is important for circadian cycling. At internal E-boxes, the MYC-MAX leucine zipper can also interact with histones H2B and H3, and its binding is indirectly enhanced by OCT4 elsewhere on the nucleosome. The nucleosomal E-box position and the type of bHLH dimerization domain jointly determine the histone contact, the affinity and the degree of competition and cooperativity with other nucleosome-bound factors.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , ADN , Histonas , Factores de Transcripción ARNTL/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , ADN/genética , ADN/metabolismo , Secuencias Hélice-Asa-Hélice/genética , Histonas/química , Histonas/metabolismo , Nucleosomas/química , Nucleosomas/genética , Nucleosomas/metabolismo , Unión Proteica , Proteínas CLOCK/química , Proteínas CLOCK/metabolismo , Proteínas Proto-Oncogénicas c-myc/química , Proteínas Proto-Oncogénicas c-myc/metabolismo , Regulación Alostérica , Leucina Zippers , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Multimerización de ProteínaRESUMEN
BACKGROUND AND PURPOSE: Sarcopenia has been demonstrated to be adversely correlated with the prognosis of various cancers. Our study aimed to estimate the prognostic value of sarcopenia in conjunction with inflammatory indices [neutrophil-to-lymphocyte ratio (NLR)] for evaluating the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing chemoradiotherapy. MATERIALS AND METHODS: This study retrospectively analyzed 255 patients with ESCC who received chemoradiotherapy from January 2012 to December 2018. Multivariate Cox regression analysis was employed to identify prognostic values of assessed factors following a novel prognostic scoring system (SMI-NLR), covering sarcopenia and NLR during different treatment courses. RESULTS: Kaplan-Meier analysis revealed significantly greater overall survival (OS) rates in the nonsarcopenia group than in the sarcopenia group (P = 0.011). The low NLR group (< 4.84) demonstrated significantly higher OS rates than the high NLR group (≥ 4.84) (P < 0.001). The SMI-NLR prognostic model was established through multivariate analysis, revealing that Karnofsky performance status [hazard ratio (HR) = 0.285; 95% confidence interval (CI) = 0.117-0.699; P = 0.006], clinical staging (HR = 5.223; 95% CI = 1.879-14.514; P = 0.002), and preSMI-NLR (HR = 0.544; 95% CI = 0.330-0.898; P = 0.017) were independent factors affecting the prognosis of patients with ESCC. Nomograms were constructed based on these data providing more accurate 1-, 3-, and 5-year survival rates for patients with ESCC. CONCLUSION: Our study indicates the effectiveness of the combined sarcopenia and NLR prognostic model for the prognostic evaluation of patients with ESCC having undergone chemoradiotherapy.
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Quimioradioterapia , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neutrófilos , Sarcopenia , Humanos , Femenino , Sarcopenia/etiología , Masculino , Quimioradioterapia/métodos , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Pronóstico , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Anciano , Linfocitos , Estimación de Kaplan-Meier , Inflamación , Adulto , Tasa de Supervivencia , Recuento de LinfocitosRESUMEN
Neurotrauma, encompassing traumatic brain injuries (TBI) and spinal cord injuries (SCI) impacts a significant portion of the global population. While spontaneous recovery post-TBI or SCI is possible, recent advancements in cell-based therapies aim to bolster these natural reparative mechanisms. Emerging research indicates that the beneficial outcomes of such therapies might be largely mediated by exosomes secreted from the administered cells. While stem cells have garnered much attention, exosomes derived from non-stem cells, including neurons, Schwann cells, microglia, and vascular endothelial cells, have shown notable therapeutic potential. These exosomes contribute to angiogenesis, neurogenesis, and axon remodeling, and display anti-inflammatory properties, marking them as promising agents for neurorestorative treatments. This review provides an in-depth exploration of the current methodologies, challenges, and future directions regarding the therapeutic role of non-stem cell-derived exosomes in neurotrauma.
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Exosomas , Células Madre Mesenquimatosas , Traumatismos de la Médula Espinal , Humanos , Células Endoteliales , Microglía , Neurogénesis , Traumatismos de la Médula Espinal/terapiaRESUMEN
Spinal cord injury (SCI) compromises the blood-spinal cord barrier (BSCB) and induces neuroinflammation, potentially exacerbating neuronal damage. This underscores the importance of maintaining BSCB integrity and mitigating neuroinflammation in SCI treatment. Our study explores an innovative approach to treating SCI by utilizing platelet-rich plasma-derived exosomes (PRP-Exos) to stabilize BSCB function and alleviate neuroinflammation. We successfully isolated exosomes from platelet-rich plasma and conducted both in vivo and in vitro experiments to assess the therapeutic effects of PRP-Exos and explore their potential mechanisms in stabilizing the BSCB, reducing neuroinflammation, and promoting neural functional recovery.In vitro results demonstrate that PRP-Exos significantly reduce the permeability of bEnd.3 cells under hypoxic-hypoglycemic conditions, thereby restoring the integrity of tight junctions. Additionally, our study elucidates the critical role of the NF-κB signaling pathway in the amelioration of neuroinflammation by PRP-Exos. In the SCI model, local injection of hydrogel-encapsulated PRP-Exos reduced Evans blue dye leakage, enhanced the expression of tight junction proteins, alleviated the inflammatory environment in the damaged area, and improved neural functional recovery. In conclusion, PRP-Exos presents a promising and effective treatment option for SCI.
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Exosomas , Enfermedades Neuroinflamatorias , Plasma Rico en Plaquetas , Traumatismos de la Médula Espinal , Médula Espinal , Traumatismos de la Médula Espinal/terapia , Exosomas/metabolismo , Plasma Rico en Plaquetas/metabolismo , Plasma Rico en Plaquetas/química , Animales , Ratones , Médula Espinal/metabolismo , Línea Celular , Masculino , Ratones Endogámicos C57BL , Barrera Hematoencefálica/metabolismo , FN-kappa B/metabolismo , Uniones Estrechas/metabolismo , Inflamación , Transducción de Señal , FemeninoRESUMEN
Based on the cross-spectral density (CSD) function, the coherence-orbital angular momentum (COAM) matrix of twisted Gaussian Schell-model (TGSM) beam is proposed, and the COAM matrix is used to describe the correlation between OAM modes in TGSM optical field. The COAM matrix characteristics of TGSM beam are analyzed by numerical simulation. The results show that the COAM matrix characteristics of TGSM beam depend on the initial parameters of the beam. In addition, a method of generating TGSM beam by superposition of COAM matrix element modes is described, and the influence of different initial parameters on the superposition characteristics is studied. The results reveal the internal relationship between the coherent structure of the optical field, the twist phase and the OAM modes. Our work helps to explore new expressions of partially coherent beams and promote the practical application of optimizing partially coherent beams.
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BACKGROUND: The growing prevalence of smartphone use among college students in China has led to health concerns, including De Quervain's Tenosynovitis (DQT). However, the specific smartphone usage behaviors contributing to DQT remain poorly understood. This study aimed to explore the relationship between smartphone usage behaviors and DQT in college students. METHODS: A cross-sectional study was conducted with 937 students from various majors in Guangxi between September 2021 and April 2022. Participants completed an online questionnaire assessing smartphone usage behaviors and their association with DQT. The Finkelstein test was employed to diagnose DQT. RESULTS: Over half of the college students (52%) tested positive for DQT via Finkelstein's test. Higher levels of smartphone usage time (6-8 h/day: OR = 4.454, 95%CI:1.662-12.229; ≥8 h/day: OR = 4.521, 95%CI:1.596-12.811), phone games (OR = 1.997, 95%CI:1.312-3.040), social media (OR = 2.263, 95%CI:1.795-3.833), and leisure activities (OR = 1.679, 95%CI:1.140-2.475) were significantly associated with an increased risk of DQT. Two specific gestures (Bilateral thumbs, BT: OR = 1.900, 95%CI:1.281-2.817; Bilateral thumbs-horizontal screen, BT-HS: OR = 1.872, 95%CI:1.244-2.818) and two screen sizes (5.0-5.5inch: OR = 2.064, 95%CI:1.108-3.846; 6.0-6.5inch: OR = 2.413, 95%CI:1.125-4.083) also exhibited a higher risk of DQT. Bilateral DQT was observed, with Gesture-BT identified as the primary risk factor. CONCLUSION: Our findings suggest that increased smartphone usage time, phone games, social media, and leisure activities elevate the risk of DQT among college students. Furthermore, two specific gestures and two screen sizes were also linked to a heightened DQT risk. To mitigate DQT development, college students should reduce smartphone usage time and adopt appropriate gestures.
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Enfermedad de De Quervain , Tenosinovitis , Humanos , Tenosinovitis/complicaciones , Enfermedad de De Quervain/complicaciones , Enfermedad de De Quervain/diagnóstico , Enfermedad de De Quervain/epidemiología , Teléfono Inteligente , Estudios Transversales , China/epidemiología , EstudiantesRESUMEN
In order to comprehensively analyze the antioxidant substances in sour jujube, total phenolic content (TPC) and total flavonoids contents (TFC) in different organs, including stem, leaf, flower, fruit pulp, and seed were analyzed for their contents and antioxidant activities. The results showed that leaves possessed significantly higher TPC and TFC (20.4 and 20.5 mg/g, respectively) than the other organs and have the highest antioxidant activity, which were also higher than the wild blueberry (A well-known for its high TPC). Subsequently, the variations in the antioxidant content and antioxidant activity of leaves were analyzed during leaf development. TPC in leaves sampled in may and august were significantly higher than that in other months, while the highest one was found in may. The n-hexane, ethyl acetate, n-butanol, and water fractions obtained from the main methanol extract of sour jujube leaves were evaluated for TPC and TFC and their antioxidant activity and it was found that ethyl acetate fraction displayed the highest TPC and TFC (184.5 and 193.3 mg/g, respectively), as well as the best antioxidant activity. In addition, using LC-MS and HPLC, ethyl acetate fraction was analyzed from qualitative and quantitative aspects; 31-one phenolic compounds, including catechin (33.0 mg/g), epigallocatechin (15.3 mg/g), quercetin 3-O-glucoside (11.4 mg/g), naringenin (6.7 mg/g), esculetin (4.8 mg/g), and chlorogenic acid (4.6 mg/g) were identified. Catechin, esculetin, epigallocatechin, chlorogenic acid, quercetin 3-O-glucoside, and naringenin exhibited high antioxidant activity. These results provide a theoretical basis for further study and utilization of flavonoid and polyphenols in sour jujube.
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Catequina , Ziziphus , Flavonoides , Antioxidantes , Quercetina , Frutas/química , Ácido Clorogénico , Extractos Vegetales , Fenoles/análisis , GlucósidosRESUMEN
Callicarpnoids A-C (1-3), three new ent-clerodane diterpenoid dimers formed via a [4 + 2] hetero Diels-Alder cycloaddition, appeared as a third example of this type of dimers, were isolated from the stems of Callicarpa arborea Roxb.. Their structures were elucidated by comprehensive spectroscopic analysis, and the absolute configurations were confirmed by single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations, as well as DP4 + analysis. Cytotoxicity test in two cell lines indicated that compounds 2 and 3 had significant cytotoxic effect against breast cancer cell (MCF-7) and colorectal cancer cell (HCT-116) with IC50 ranging from 5.2 to 7.2 µM, comparable to those of the positive control. Furthermore, the western blot analysis revealed that the protein expression levels of Bax were increased following compounds 2 and 3 treatment, whereas the expression levels of caspase 8, caspase 3, caspase 9 and Bcl2 were decreased in a dose-dependent manner, indicating that compounds 2 and 3 may induce apoptosis via both intrinsic and extrinsic pathways in MCF-7 and HCT-116 cells.
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Callicarpa , Diterpenos de Tipo Clerodano , Humanos , Diterpenos de Tipo Clerodano/farmacología , Células MCF-7 , Células HCT116 , Apoptosis , Estructura MolecularRESUMEN
Two NhaD-type antiporters, NhaD1 and NhaD2, from the halotolerant and alkaliphilic Halomonas sp. strain Y2, exhibit different physiological functions in regard to Na+ and Li+ resistance, although they share high sequence identity. In the present study, the truncation of an additional 4 C-terminal residues from NhaD2 or an exchange of 39 N-terminal residues between these proteins resulted in the complete loss of antiporter activity. Interestingly, combining 39 N-terminal residues and 7 C-terminal residues of NhaD2 (N39D2-C7) partially recovered the activity for Na+ and Li+ expulsion, as well as complementary growth following exposure to 300 mM Na+ and 100 mM Li+ stress. The recovered activity of chimera N39D2-C7 indicated that the N and C termini are structurally dependent on each other and function synergistically. Furthermore, fluorescence resonance energy transfer (FRET) analysis suggested that the N and C termini are relatively close in proximity which may account for their synergistic function in ion translocation. In the N-terminal region of N39D2-C7, the replacement of Glu38 with Pro abolished the recovered complementary and transport activities. In addition, this amino acid substitution in NhaD2 resulted in a drastically decreased complementation ability in Escherichia coli KNabc (level identical to that of NhaD1), as well as decreased activity and an altered pH profile.IMPORTANCE Limited information on NhaD antiporters supports speculation that these antiporters are important for resistance to high salinity and alkalinity. Moreover, only a few functional residues have been identified in NhaD antiporters, and there is limited literature on the molecular mechanisms of NhaD antiporter activity. The altered antiporter abilities of chimeras and mutants in this study implicate the functions of the N and C termini, especially Glu38, in pH regulation and ion translocation, and, most importantly, the essential roles of this negatively charged residue in maintaining the physiological function of NhaD2. These findings further our understanding of the molecular mechanism of NhaD antiporters for ion transport.
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Antiportadores/metabolismo , Halomonas/enzimología , Secuencia de Aminoácidos , Antiportadores/química , Antiportadores/genética , Análisis Mutacional de ADN , Escherichia coli/genética , Prueba de Complementación Genética , Halomonas/genética , Halomonas/metabolismo , Modelos Moleculares , Unión Proteica , Conformación Proteica , Recombinación Genética , Eliminación de Secuencia , Homología de Secuencia de AminoácidoRESUMEN
Cooperation between the circadian transcription factor (TF) CLOCK:BMAL1 and other TFs at cis-regulatory elements (CREs) is critical to daily rhythms of transcription. Yet, the modalities of this cooperation are unclear. Here, we analyzed the co-binding of multiple TFs on single DNA molecules in mouse liver using single molecule footprinting (SMF). We found that SMF reads clustered in stereotypic chromatin states that reflect distinguishable organization of TFs and nucleosomes, and that were remarkably conserved between all samples. DNA protection at CLOCK:BMAL1 binding motif (E-box) varied between CREs, from E-boxes being solely bound by CLOCK:BMAL1 to situations where other TFs competed with CLOCK:BMAL1 for E-box binding. SMF also uncovered CLOCK:BMAL1 cooperative binding at E-boxes separated by 250 bp, which structurally altered the CLOCK:BMAL1-DNA interface. Importantly, we discovered multiple nucleosomes with E-boxes at entry/exit sites that were removed upon CLOCK:BMAL1 DNA binding, thereby promoting the formation of open chromatin states that facilitate DNA binding of other TFs and that were associated with rhythmic transcription. These results demonstrate the utility of SMF for studying how CLOCK:BMAL1 and other TFs regulate stereotypical chromatin states at CREs to promote transcription.
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Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine disorder that implicates a spectrum of clinical manifestations, including hormonal imbalance, metabolic dysfunction, and even compromised ovarian granulosa cell (GC) activity. The underlying molecular mechanisms of PCOS remain elusive, presenting a significant barrier to effective diagnosis and treatment. This review delves into the emerging role of long non-coding RNAs (lncRNAs) in the pathophysiology of PCOS, articulating their intricate interactions with mRNAs, microRNAs, and other epigenetic regulators that collectively influence the hormonal and metabolic milieu of PCOS. We examine the dynamic regulatory networks orchestrated by lncRNAs that impact GC function, steroidogenesis, insulin resistance, and inflammatory pathways. By integrating findings from recent studies, we illuminate the potential of lncRNAs as biomarkers for PCOS and highlight their contribution to the disorder, offering a detailed perspective on the lncRNA-mediated modulation of gene expression and pathogenic pathways. Understanding targeted lncRNA interactions with PCOS proposes novel avenues for therapeutic intervention to ameliorate the reproductive and metabolic disturbances characteristic of the syndrome.
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The short association fibers or U-fibers travel in the superficial white matter (SWM) beneath the cortical layer. While the U-fibers play a crucial role in various brain disorders, there is a lack of effective tools to reconstruct their highly curved trajectory from diffusion MRI (dMRI). In this work, we propose a novel surface-based framework for the probabilistic tracking of fibers on the triangular mesh representation of the SWM. By deriving a closed-form solution to transform the spherical harmonics (SPHARM) coefficients of 3D fiber orientation distributions (FODs) to local coordinate systems on each triangle, we develop a novel approach to project the FODs onto the tangent space of the SWM. After that, we utilize parallel transport to realize the intrinsic propagation of streamlines on SWM following probabilistically sampled fiber directions. Our intrinsic and surface-based method eliminates the need to perform the necessary but challenging sharp turns in 3D compared with conventional volume-based tractography methods. Using data from the Human Connectome Project (HCP), we performed quantitative comparisons to demonstrate the proposed algorithm can more effectively reconstruct the U-fibers connecting the precentral and postcentral gyrus than previous methods. Quantitative validations were then performed on post-mortem MRIs to show the reconstructed U-fibers from our method more faithfully follow the SWM than volume-based tractography. Finally, we applied our algorithm to study the parietal U-fiber connectivity changes in autosomal dominant Alzheimer's disease (ADAD) patients and successfully detected significant associations between U-fiber connectivity and disease severity.
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Conectoma , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Fibras Nerviosas , Conectoma/métodos , Encéfalo/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
OBJECTIVE: We assessed the impact and prognostic significance of alterations in muscle quality and quantity (myosteatosis and sarcopenia, respectively) in patients with esophageal cancer treated with radiotherapy (RT). METHODS: We retrospectively pooled 258 patients with esophageal squamous cell cancer who underwent RT. Myosteatosis and sarcopenia were determined based on the skeletal muscle index derived from the muscle area and attenuation at the L3 level from computed tomography images. Subgroups were formed as 2 subgroups of non-sarcopenia/myosteatosis and sarcopenia/myosteatosis (with or without other muscle status) at either timepoint of RT, 3 subgroups of only-sarcopenia, only myosteatosis (without other muscle status), and the co-presence of sarcopenia and myosteatosis at either timepoint of RT, as well as 4 subgroups of continuous sarcopenia/myosteatosis, developed sarcopenia/myosteatosis, reduced sarcopenia/myosteatosis and non-sarcopenia/myosteatosis according to alterations of muscle status at both timepoints of RT. Overall survival (OS) was compared. Univariate and multivariate analyses based on Cox regression identified independent risk factors for prognosis. RESULTS: Either pre- or post-RT, patients with sarcopenia and myosteatosis (with or without other muscle status) had poor OS. Patients with only myosteatosis (without other muscle status) showed the best OS (1352 days pre-RT vs. 1648 days post-RT), while patients with concurrent myosteatosis and sarcopenia had the worst OS (907 days pre-RT vs. 706 days post-RT). The ascending order of OS for sarcopenia alterations was as follows: continuous sarcopenia (1093 days), non-sarcopenia (1740 days), developed sarcopenia (2187 days), and reduced sarcopenia (2208 days) (P = 0.002). The ascending order of OS for myosteatosis alterations was ranked as follows: continuous myosteatosis (1165 days), reduced myosteatosis (1275 days), developed myosteatosis (1783 days), and non-myosteatosis (1942 days) (P = 0.061). Univariate and multivariate Cox regression analyses revealed that increased age, longer tumor length, developed myosteatosis, and continuous myosteatosis were independent prognostic factors for OS. CONCLUSIONS: Muscle mass status at presentation and alterations in patients with esophageal cancer before and after RT should be considered prognostic indicators.
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Polyetheretherketone (PEEK) material has become a potential bone replacement material due to its elastic modulus, which is close to that of human bone, and stable chemical properties. However, its biological inertness has hindered its clinical application. To improve the biological inertia of PEEK material, a hyaluronic acid (HA) hydrogel coating loaded with platelet-rich plasma (PRP) and nerve growth factor (NGF) was constructed on the surface of PEEK material in this study. After the hybrid hydrogel coating was constructed, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), degradation tests, and enzyme-linked immunosorbent assays (ELISAs) were used to evaluate its characteristics and biological properties. The osteogenic and angiogenic potentials were also investigated in vitro and in vivo. Our results showed that the HA hydrogel loaded with RPP and NGF on the PEEK surface degraded slowly and could sustainably release various growth factors, including NGF. The results of in vitro tests showed that the hybrid hydrogel on the surface of PEEK effectively promoted osteogenesis and angiogenesis. The in vivo experiment also confirmed that the PEEK surface hydrogel could promote osseointegration of the implant and the integration of new bone and neovascularization. Our results suggest that the cross-linked hyaluronic acid hydrogel loaded with PRP and NGF can significantly improve the biological inertia of PEEK material, endowing PEEK material with good osteogenic and angiogenic ability.
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[This corrects the article DOI: 10.1016/j.mtbio.2023.100928.].
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BACKGROUND: Tibial Cortex Transverse Transport (TTT) represents an innovative surgical method for treating lower extremity diabetic foot ulcers (DFUs), yet its underlying mechanisms remain elusive. Establishing an animal model that closely mirrors clinical scenarios is both critical and novel for elucidating the mechanisms of TTT. METHODS: We established a diabetic rat model with induced hindlimb ischemia to mimic the clinical manifestation of DFUs. TTT was applied using an external fixator for regulated bone movement. Treatment efficacy was evaluated through wound healing assessments, histological analyses, and immunohistochemical techniques to elucidate biological processes. RESULTS: The TTT group demonstrated expedited wound healing, improved skin tissue regeneration, and diminished inflammation relative to controls. Marked neovascularization and upregulation of angiogenic factors were observed, with the HIF-1α/SDF-1/CXCR4 pathway and an increase in EPCs being pivotal in these processes. A transition toward anti-inflammatory M2 macrophages indicated TTT's immunomodulatory capacity. CONCLUSION: Our innovative rat model effectively demonstrates the therapeutic potential of TTT in treating DFUs. We identified TTT's roles in promoting angiogenesis and modulating the immune system. This paves the way for further in-depth research and potential clinical applications to improve DFU management strategies.
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Diabetes Mellitus , Pie Diabético , Animales , Ratas , Pie Diabético/terapia , Angiogénesis , Tibia , Inflamación , PieRESUMEN
Purpose: Management of severe diabetic foot ulcers (DFUs) remains challenging. Tibial cortex transverse transport (TTT) facilitates healing and limb salvage in patients with recalcitrant DFUs. However, the underlying mechanism is largely unknown, necessitating the establishment of an animal model and mechanism exploration. Methods: Severe DFUs were induced in rats, then assigned to TTT, sham, or control groups (n=16/group). The TTT group underwent a tibial corticotomy, with 6 days each of medial and lateral transport; the sham group had a corticotomy without transport. Ulcer healing was assessed through Laser Doppler, CT angiography, histology, and immunohistochemistry. Serum HIF-1α, PDGF-BB, SDF-1, and VEGF levels were measured by ELISA. Results: The TTT group showed lower percentages of wound area, higher dermis thickness (all p < 0.001 expect for p = 0.001 for TTT vs Sham at day 6) and percentage of collagen content (all p < 0.001) than the other two groups. The TTT group had higher perfusion and vessel volume in the hindlimb (all p < 0.001). The number of CD31+ cells (all p < 0.001) and VEGFR2+ cells (at day 6, TTT vs Control, p = 0.001, TTT vs Sham, p = 0.006; at day 12, TTT vs Control, p = 0.003, TTT vs Sham, p = 0.01) were higher in the TTT group. The activity of HIF-1α, PDGF-BB, and SDF-1 was increased in the TTT group (all p < 0.001 except for SDF-1 at day 12, TTT vs Sham, p = 0.005). The TTT group had higher levels of HIF-1α, PDGF-BB, SDF-1, and VEGF in serum than the other groups (all p < 0.001). Conclusion: TTT enhanced neovascularization and perfusion at the hindlimb and accelerated healing of the severe DFUs. The underlying mechanism is related to HIF-1α-induced angiogenesis.
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The fiber orientation distribution function (FOD) is an advanced model for high angular resolution diffusion MRI representing complex fiber geometry. However, the complicated mathematical structures of the FOD function pose challenges for FOD image processing tasks such as interpolation, which plays a critical role in the propagation of fiber tracts in tractography. In FOD-based tractography, linear interpolation is commonly used for numerical efficiency, but it is prone to generate false artificial information, leading to anatomically incorrect fiber tracts. To overcome this difficulty, we propose a flowbased and geometrically consistent interpolation framework that considers peak-wise rotations of FODs within the neighborhood of each location. Our method decomposes a FOD function into multiple components and uses a smooth vector field to model the flows of each peak in its neighborhood. To generate the interpolated result along the flow of each vector field, we develop a closed-form and efficient method to rotate FOD peaks in neighboring voxels and realize geometrically consistent interpolation of FOD components. By combining the interpolation results from each peak, we obtain the final interpolation of FODs. Experimental results on Human Connectome Project (HCP) data demonstrate that our method produces anatomically more meaningful FOD interpolations and significantly enhances tractography performance.
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Superficial white matter (SWM) plays an important role in functioning of the human brain, and it contains a large amount of cortico-cortical connections. However, the difficulties of generating complete and reliable U-fibers make SWM-related analysis lag behind relatively matured Deep white matter (DWM) analysis. With the aid of some newly proposed surface-based SWM tractography algorithms, we have developed a specialized SWM filtering method based on a symmetric variational autoencoder (VAE). In this work, we first demonstrate the advantage of the spherical representation and generate these spherical tracts using the triangular mesh and the registered spherical surface. We then introduce the Filtering via symmetric Autoencoder for Spherical Superficial White Matter tractography (FASSt) framework with a novel symmetric weights module to perform the filtering task in a latent space. We evaluate and compare our method with the state-of-the-art clustering-based method on diffusion MRI data from Human Connectome Project (HCP). The results show that our proposed method outperform these clustering methods and achieves excellent performance in groupwise consistency and topographic regularity.
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The sustainable development of infrastructure construction projects heavily depends on favorable cooperation of all parties and ethical code of conduct, while Un-ethical pro-organizational behavior (UPB) may undermine the mutual efforts and cause serious consequences. UPB has aroused wide interest of researchers, but what may trigger construction employees to engage in UPB at team-level has not been elucidated completely. With information asymmetry and huge uncertainty, the behaviors of employees in temporary project teams are marked by environmental and personal characters. The study discusses the influences of collective moral judgement focus on self (CMJS) and Machiavellianism on UPB. Through a moderated mediation analysis conducted on a set of survey data from Chinese construction projects, the empirical results of the two-level hierarchical linear model indicate that CMJS positively impacts UPB directly, and meanwhile Machiavellianism acts as a partial mediator in the relationship between CMJS and UPB. The findings also reveal that performance-avoidance goal orientation (PAGO) and motivation to learn (MTL) moderate and strengthen the relationship between Machiavellianism and UPB. The study offers practical suggestions for both project managers and policymakers of construction projects.