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1.
Proc Natl Acad Sci U S A ; 120(19): e2219098120, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37126725

RESUMO

Graphene oxide (GO) membranes with nanoconfined interlayer channels theoretically enable anomalous nanofluid transport for ultrahigh filtration performance. However, it is still a significant challenge for current GO laminar membranes to achieve ultrafast water permeation and high ion rejection simultaneously, because of the contradictory effect that exists between the water-membrane hydrogen-bond interaction and the ion-membrane electrostatic interaction. Here, we report a vertically aligned reduced GO (VARGO) membrane and propose an electropolarization strategy for regulating the interfacial hydrogen-bond and electrostatic interactions to concurrently enhance water permeation and ion rejection. The membrane with an electro-assistance of 2.5 V exhibited an ultrahigh water permeance of 684.9 L m-2 h-1 bar-1, which is 1-2 orders of magnitude higher than those of reported GO-based laminar membranes. Meanwhile, the rejection rate of the membrane for NaCl was as high as 88.7%, outperforming most reported graphene-based membranes (typically 10 to 50%). Molecular dynamics simulations and density-function theory calculations revealed that the electropolarized VARGO nanochannels induced the well-ordered arrangement of nanoconfined water molecules, increasing the water transport efficiency, and thereby resulting in improved water permeation. Moreover, the electropolarization effect enhanced the surface electron density of the VARGO nanochannels and reinforced the interfacial attractive interactions between the cations in water and the oxygen groups and π-electrons on the VARGO surface, strengthening the ion-partitioning and Donnan effect for the electrostatic exclusion of ions. This finding offers an electroregulation strategy for membranes to achieve both high water permeability and high ion rejection performance.

2.
FASEB J ; 38(4): e23490, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38363581

RESUMO

Appropriate Ca2+ concentration in the endoplasmic reticulum (ER), modulating cytosolic Ca2+ signal, serves significant roles in physiological function of pancreatic ß cells. To maintaining ER homeostasis, Ca2+ movement across the ER membrane is always accompanied by a simultaneous K+ flux in the opposite direction. KCNH6 was proven to modulate insulin secretion by controlling plasma membrane action potential duration and intracellular Ca2+ influx. Meanwhile, the specific function of KCNH6 in pancreatic ß-cells remains unclear. In this study, we found that KCNH6 exhibited mainly ER localization and Kcnh6 ß-cell-specific knockout (ßKO) mice suffered from abnormal glucose tolerance and impaired insulin secretion in adulthood. ER Ca2+ store was overloaded in islets of ßKO mice, which contributed to ER stress and ER stress-induced apoptosis in ß cells. Next, we verified that ethanol treatment induced increases in ER Ca2+ store and apoptosis in pancreatic ß cells, whereas adenovirus-mediated KCNH6 overexpression in islets attenuated ethanol-induced ER stress and apoptosis. In addition, tail-vein injections of KCNH6 lentivirus rescued KCNH6 expression in ßKO mice, restored ER Ca2+ overload and attenuated ER stress in ß cells, which further confirms that KCNH6 protects islets from ER stress and apoptosis. These data suggest that KCNH6 on the ER membrane may help to stabilize intracellular ER Ca2+ stores and protect ß cells from ER stress and apoptosis. In conclusion, our study reveals the protective potential of KCNH6-targeting drugs in ER stress-induced diabetes.


Assuntos
Diabetes Mellitus , Células Secretoras de Insulina , Camundongos , Animais , Secreção de Insulina , Diabetes Mellitus/metabolismo , Células Secretoras de Insulina/metabolismo , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Cálcio/metabolismo , Etanol , Insulina/metabolismo
3.
Cell Mol Life Sci ; 81(1): 86, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349432

RESUMO

Glucose-stimulated insulin secretion (GSIS) in pancreatic islet ß-cells primarily relies on electrophysiological processes. Previous research highlighted the regulatory role of KCNH6, a member of the Kv channel family, in governing GSIS through its influence on ß-cell electrophysiology. In this study, we unveil a novel facet of KCNH6's function concerning insulin granule exocytosis, independent of its conventional electrical role. Young mice with ß-cell-specific KCNH6 knockout (ßKO) exhibited impaired glucose tolerance and reduced insulin secretion, a phenomenon not explained by electrophysiological processes alone. Consistently, islets from KCNH6-ßKO mice exhibited reduced insulin secretion, conversely, the overexpression of KCNH6 in murine pancreatic islets significantly enhanced insulin release. Moreover, insulin granules lacking KCNH6 demonstrated compromised docking capabilities and a reduced fusion response upon glucose stimulation. Crucially, our investigation unveiled a significant interaction between KCNH6 and the SNARE protein regulator, Munc18-1, a key mediator of insulin granule exocytosis. These findings underscore the critical role of KCNH6 in the regulation of insulin secretion through its interaction with Munc18-1, providing a promising and novel avenue for enhancing our understanding of the Kv channel in diabetes mechanisms.


Assuntos
Exocitose , Insulina , Animais , Camundongos , Fenômenos Eletrofisiológicos , Glucose , Secreção de Insulina
4.
Genomics ; 116(5): 110889, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901654

RESUMO

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

5.
J Biol Chem ; 299(4): 103045, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36822326

RESUMO

Glucose-stimulated insulin secretion of pancreatic ß cells is essential in maintaining glucose homeostasis. Recent evidence suggests that the Nephrin-mediated intercellular junction between ß cells is implicated in the regulation of insulin secretion. However, the underlying mechanisms are only partially characterized. Herein we report that GIV is a signaling mediator coordinating glucose-stimulated Nephrin phosphorylation and endocytosis with insulin secretion. We demonstrate that GIV is expressed in mouse islets and cultured ß cells. The loss of function study suggests that GIV is essential for the second phase of glucose-stimulated insulin secretion. Next, we demonstrate that GIV mediates the high glucose-stimulated tyrosine phosphorylation of GIV and Nephrin by recruiting Src kinase, which leads to the endocytosis of Nephrin. Subsequently, the glucose-induced GIV/Nephrin/Src signaling events trigger downstream Akt phosphorylation, which activates Rac1-mediated cytoskeleton reorganization, allowing insulin secretory granules to access the plasma membrane for the second-phase secretion. Finally, we found that GIV is downregulated in the islets isolated from diabetic mice, and rescue of GIV ameliorates the ß-cell dysfunction to restore the glucose-stimulated insulin secretion. We conclude that the GIV/Nephrin/Akt signaling axis is vital to regulate glucose-stimulated insulin secretion. This mechanism might be further targeted for therapeutic intervention of diabetic mellitus.


Assuntos
Diabetes Mellitus Experimental , Células Secretoras de Insulina , Ilhotas Pancreáticas , Animais , Camundongos , Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Transporte Vesicular/metabolismo
6.
Biochem Biophys Res Commun ; 736: 150504, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39121673

RESUMO

BACKGROUND & AIMS: Primary Hepatic Neuroendocrine Carcinoma (PHNEC) is a rare and aggressive tumor with high recurrence rates. Surgical resection remains the only therapeutic strategy. The effectiveness of tyrosine kinase inhibitors (TKIs) for PHNEC remains unclear due to limited research. METHODS: We employed immunohistochemical staining to diagnose PHNEC and assess the expression of eight tyrosine kinase receptors in tumor tissues, including VEGFRs, PDGFRA, EGFR, FGFRs et al. A patient-derived xenograft (PDX) model was established using PHNEC tumor tissues to test the efficacy of TKIs. PDX mice bearing tumors were treated with Avapritinib, an FDA-approved PDGFRA-targeting drug, at a daily oral dose of 10 mg/kg for 2 weeks. RESULTS: Pathological analysis confirmed the diagnosis of PHNEC with positive expression of Neural cell adhesion molecule (NCAM/CD56), Synaptophysin (Syn), and Somatostatin receptor 2 (SSTR-2), and negative expression of Hep (Hepatocyte Paraffin 1), a biomarker for Hepatocellular carcinoma. Notably, PDGFRA was significantly overexpressed in PHNEC tumor tissues compared to other tyrosine kinases. Avapritinib treatment significantly reduced tumor growth in PDX mice by 73.9 % (p = 0.008). Additionally, Avapritinib treatment led to a marked decrease in PDGFRA and Ki-67 expression, suggesting that it inhibits tumor cell proliferation by suppressing PDGFRA. CONCLUSION: Our findings suggest that PDGFRA is a potential therapeutic target for PHNEC, and its inhibition with Avapritinib may offer clinical benefits to patients with this rare malignancy.

7.
Phys Rev Lett ; 133(4): 043401, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39121402

RESUMO

We report on an experimental simulation of the spin-1 Heisenberg model with composite bosons in a one-dimensional chain based on the two-component Bose-Hubbard model. Exploiting our site- and spin-resolved quantum gas microscope, we observed faster superexchange dynamics of the spin-1 system compared to its spin-1/2 counterpart, which is attributed to the enhancement effect of multi-bosons. We further probed the nonequilibrium spin dynamics driven by the superexchange and single-ion anisotropy terms, unveiling the linear expansion of the spin-spin correlations, which is limited by the Lieb-Robinson bound. Based on the superexchange process, we prepared and verified the entangled qutrits pairs with these composite spin-1 bosons, potentially being applied in qutrit-based quantum information processing.

8.
Acta Derm Venereol ; 104: adv23901, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38751176

RESUMO

Telemedicine, the provision of remote healthcare, has gained prominence, accelerated by the COVID-19 pandemic. It has the potential to replace routine in-person follow-up visits for patients with chronic inflammatory skin conditions. However, it remains unclear whether telemedicine can effectively substitute in-person consultations for this patient group. This systematic review assessed the effectiveness and safety of telemedicine compared with traditional in-person care for chronic inflammatory skin diseases. A comprehensive search in various databases identified 11 articles, including 5 randomized controlled trials (RCTs) and 1 clinical controlled trial (CCT). These studies evaluated telemedicine's impact on patients with psoriasis and atopic dermatitis, with varying methods like video consultations and digital platforms. The findings tentatively suggest that telemedicine does not seem to be inferior compared with in-person care, particularly in terms of condition severity and quality of life for patients with chronic inflammatory skin diseases. However, these results should be interpreted with caution due to the inherent uncertainties in the evidence. There are indications that telemedicine can offer benefits such as cost-effectiveness, time savings, and reduced travel distances, but it is important to recognize these findings as preliminary, necessitating further validation through more extensive research.


Assuntos
COVID-19 , Telemedicina , Humanos , Telemedicina/métodos , COVID-19/epidemiologia , Doença Crônica , Psoríase/terapia , Qualidade de Vida , Dermatite Atópica/terapia , Dermatite Atópica/diagnóstico , SARS-CoV-2
9.
J Nanobiotechnology ; 22(1): 464, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095755

RESUMO

BACKGROUND: Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity. RESULTS: We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs. CONCLUSIONS: Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.


Assuntos
Cardiotoxicidade , Doxorrubicina , Exossomos , Momordica charantia , Fator 2 Relacionado a NF-E2 , Animais , Cardiotoxicidade/prevenção & controle , Cardiotoxicidade/metabolismo , Momordica charantia/química , Exossomos/metabolismo , Ratos , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ratos Sprague-Dawley , Proteína Sequestossoma-1/metabolismo
10.
Arch Orthop Trauma Surg ; 144(4): 1547-1556, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38386063

RESUMO

INTRODUCTION: Various surgical techniques have been proposed to manage acetabular fractures involving both columns with posterior wall displacement. However, the optimal surgical approach to achieve satisfactory reduction quality remains controversial. MATERIALS AND METHODS: This retrospective study evaluated 34 patients with fractures who were treated at a single medical institution. The patients were divided into two groups according to the ventral/dorsal surgical approach employed: simultaneous (SI) and sequential (SE). Perioperative parameters, as well as radiological and functional outcomes, were analyzed and compared between the two groups. RESULTS: The SI and SE groups comprised 9 and 23 out of the 34 patients, respectively. The SI group exhibited a significantly shorter surgical time and lower estimated blood loss than the SE group (p = 0.04 and 0.03, respectively). The quality of reductions of the anterior and posterior columns was similar between the two groups; however, superior reduction in the fracture gap of the posterior wall was observed in the SI group, as revealed by axial and coronal computed tomography scans. CONCLUSIONS: A simultaneous ventral and dorsal approach through the pararectus and the modified Gibson approach confer clinical advantages in reducing the fracture gap, surgical time, and intraoperative blood loss when managing acetabular fractures involving both columns and a displaced posterior wall. Therefore, these surgical approaches may be considered to be optimal for achieving satisfactory reduction quality in such fractures.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Humanos , Fixação Interna de Fraturas/métodos , Estudos Retrospectivos , Resultado do Tratamento , Acetábulo/lesões , Fraturas do Quadril/cirurgia , Fraturas Ósseas/cirurgia
11.
Zhongguo Zhong Yao Za Zhi ; 49(17): 4711-4722, 2024 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-39307819

RESUMO

The study aims to evaluate the effect of Kaixin Powder(KXP) on the behavior and brain tissue of chemotherapy-treated mice to explore its mechanism in alleviating chemotherapy-induced cognitive impairment in tumor-bearing mice. Thirty female BALB/c mice were inoculated with 4T1 breast cancer cells to establish a tumor-bearing mouse model and randomly divided into the tumor group, a doxorubicin group, and a KXP group. Behavioral tests, including open field test, elevated plus maze test, forced swimming test, tail suspension test, Morris water maze test, and novel object recognition test, were conducted. Pathological examinations, including hematoxylin-eosin staining, Nissl staining, toluidine blue staining, Fluoro-Jade B staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay, immunofluorescence staining, and transmission electron microscopy, were performed. Network pharmacology and whole transcriptome sequencing methods were used to analyze the mechanism of chemotherapy-induced cognitive impairment and the targets of KXP. The results showed that KXP prevented chemotherapy-induced behavioral changes(P<0.001), increased the total movement distance and central zone residence time in the open field test, increased exploration time in the open arm area in the elevated plus maze test, reduced immobility time in the forced swimming test and tail suspension test, reduced escape latency in the Morris water maze test and increased platform crossings, and improved cognitive index in the novel object recognition test. KXP also inhibited chemotherapy-induced neuroinflammation, apoptosis, and autophagy in the prefrontal cortex, and reshaped the RNA expression profile of the prefrontal cortex tissue during chemotherapy(P<0.05). In conclusion, KXP may alleviate chemotherapy-induced cognitive impairment in tumor-bearing mice by reshaping the RNA expression profile of prefrontal cortex tissue, thereby reducing neuronal tissue damage.


Assuntos
Neoplasias da Mama , Medicamentos de Ervas Chinesas , Camundongos Endogâmicos BALB C , Animais , Feminino , Camundongos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/genética , Disfunção Cognitiva/tratamento farmacológico , Humanos , Comprometimento Cognitivo Relacionado à Quimioterapia/genética , Comprometimento Cognitivo Relacionado à Quimioterapia/tratamento farmacológico , Comprometimento Cognitivo Relacionado à Quimioterapia/metabolismo , Transcriptoma/efeitos dos fármacos , Pós/química , Perfilação da Expressão Gênica , Apoptose/efeitos dos fármacos , Antineoplásicos/efeitos adversos
12.
Anal Chem ; 95(18): 7336-7343, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37129510

RESUMO

Rapid and accurate detection of biomolecules is of vital importance for the diagnosis of disease and for performing timely treatments. The point-of-care analysis of cancer biomarkers in the blood with low cost and easy processing is still challenging. Herein, an advanced and robust strategy, which integrates the buoyant recognition probe with the magnetic reporter probe in one solution, was first proposed for immobilization-free electrochemical immunosensing. The tumor marker of alpha fetoprotein (AFP) can be captured immune-buoyantly, and then a multifunctional magnetic reporter probe in pseudo-homogeneous solution was further captured to fulfill a sandwich-type immunoreaction. The residual magnetic reporter probe can be firmly and efficiently attracted on a magnetic glassy carbon electrode to fulfill the conversion of the target AFP amount into the residual magnetic electrochemical signal indicator. As a result, the electrochemical signal of methylene blue can accurately reflect the original level of target antigen AFP concentration. By integrating buoyancy-driven quasi-homogenous biorecognition with magnetism-mediated amplification and signal output, the proposed immobilization-free electrochemical immunosensing strategy displayed a wide range of linear response (100 fg mL-1 to 10 ng mL-1), low detection limit (14.52 fg mL-1), and good reproducibility, selectivity, and stability. The designed strategy manifests remarkable advantages including assay simplicity, rapidness, and high sensitivity owing to the in-solution instead of on-electrode biorecognition that could accelerate and improve the biorecognition efficiency. To the best of our knowledge, this is the first cooperation of buoyancy-driven biorecognition with magnetism-mediated signal output in bioanalysis, which would be attractive for rapid clinic biomedical application. Thus, this work provides a fresh perspective for convenient and favorable immobilization-free electrochemical biosensing of universal biomolecules.


Assuntos
Técnicas Biossensoriais , alfa-Fetoproteínas , alfa-Fetoproteínas/análise , Técnicas Eletroquímicas , Reprodutibilidade dos Testes , Biomarcadores Tumorais/análise , Limite de Detecção , Imunoensaio , Ouro/química
13.
Phys Rev Lett ; 131(7): 073401, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37656862

RESUMO

Ultracold atoms in optical lattices form a competitive candidate for quantum computation owing to the excellent coherence properties, the highly parallel operations over spins, and the ultralow entropy achieved in qubit arrays. For this, a massive number of parallel entangled atom pairs have been realized in superlattices. However, the more formidable challenge is to scale up and detect multipartite entanglement, the basic resource for quantum computation, due to the lack of manipulations over local atomic spins in retroreflected bichromatic superlattices. In this Letter, we realize the functional building blocks in quantum-gate-based architecture by developing a cross-angle spin-dependent optical superlattice for implementing layers of quantum gates over moderately separated atoms incorporated with a quantum gas microscope for single-atom manipulation and detection. Bell states with a fidelity of 95.6(5)% and a lifetime of 2.20±0.13 s are prepared in parallel, and then connected to multipartite entangled states of one-dimensional ten-atom chains and two-dimensional plaquettes of 2×4 atoms. The multipartite entanglement is further verified with full bipartite nonseparability criteria. This offers a new platform toward scalable quantum computation and simulation.

14.
Biomed Eng Online ; 22(1): 42, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37161417

RESUMO

BACKGROUND: Although minimally invasive surgeries have gained popularity in many orthopaedic fields, minimally invasive approaches for diaphyseal clavicular fracture have not been widely performed, which is attributed to difficulties in performing a closed reduction of fracture deformities of a curved bone in a three-dimensional space. The goal of this study was to investigate the radiographic parameters of fracture deformities in a three-dimensional space and to identify the risk factors for deformities. METHODS: The computed tomography images of 100 patients who sustained a clavicle fracture were included. Five parameters were used to analyze the deformities: change in clavicle length, fracture displacement, and fragment rotation around the X, Y, Z axes. The change in length was assessed using the length of the endpoint line. The displacement was assessed using the distance between the fracture midpoints. The rotation deformities were assessed using the Euler angles. The correlation between the parameters was evaluated with the Pearson correlation coefficient. The risk factors were evaluated using univariable analysis and multiple regression analysis. RESULTS: The average change in length was - 5.3 ± 8.3 mm. The displacement was 11.8 ± 7.1 mm. The Euler angles in the Z-Y-X sequences were -1 ± 8, 1 ± 8, and - 8 ± 13 degrees. The correlation coefficient between the change in length and the displacement was - 0.724 (p < 0.001). The variables found to increase the risk of shortening and displacement were right-sided fracture (p = 0.037), male sex (p = 0.015), and multifragmentary type (p = 0.020). The variables found to increase the risk of rotation deformity were the number of rib fractures (p = 0.001) and scapula fracture (p = 0.025). CONCLUSIONS: There was a strong correlation between shortening and displacement. The magnitude of anterorotation around the X axis was greater than the magnitude of retraction around the Z axis and depression around the Y axis. The risk factors for shortening and displacement included right-sided fracture, male sex, and multifragmentary type. The risk factor for retraction around the Z axis was the number of rib fractures, and the risk factor for depression around the Y axis was scapula fracture. These results could be useful adjuncts in guiding minimally invasive surgical planning for diaphyseal clavicular fractures.


Assuntos
Ortopedia , Fraturas das Costelas , Fraturas do Ombro , Traumatismos Torácicos , Humanos , Masculino , Clavícula/diagnóstico por imagem , Fatores de Risco
15.
World J Surg ; 47(4): 903-911, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36567348

RESUMO

BACKGROUND: Reasons for the increased use of closed reduction and internal fixation (CRIF) for traumatic sacral fractures (SFs) are unclear in the literature. Therefore, we aimed to report the annual changes in the number of patients, mechanisms of injury, fracture patterns, and fixation methods. METHODS: In this retrospective study, we extracted data of 271 patients (mean age, 37.5 years) from the trauma register over an 8-year period. Annual records regarding the number of patients, injury mechanisms, fracture types, and treatment options were statistically analyzed to examine the interactions among these factors. RESULTS: The number of patients with SFs increased significantly each year. The rate of admission to the intensive care unit after resuscitation was high (64.9%). Arbeitsgemeinschaft für Osteosynthesefragen (AO) type C pelvic ring injury (PRI), Dennis zone II injury, Roy-Camille type 2 injury, and U/H-type injury were the most common fracture types. Trans-iliac trans-sacral screws were mainly used in AO type B PRI, and their use significantly increased each year. For AO type C PRI, open reduction and internal fixation (ORIF) with rigid fixation was the main treatment, and the use of CRIF with iliosacral screws decreased each year. Stepwise statistical analysis revealed that the increase in AO type B PRI and ORIF for anterior PRI were the factors contributing to the increased use of CRIF for SFs. CONCLUSIONS: While the use of osteosynthesis for SFs is increasing, an increased use of CRIF for traumatic SFs has also been observed in clinical practice. This increase can be attributed to the increase in AO type B PRIs and ORIF for anterior PRIs.


Assuntos
Fraturas Ósseas , Lesões do Pescoço , Ossos Pélvicos , Humanos , Adulto , Estudos Retrospectivos , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/métodos , Sacro/cirurgia , Sacro/lesões , Redução Aberta , Resultado do Tratamento , Ossos Pélvicos/lesões
16.
Mol Ther ; 30(8): 2709-2721, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35477658

RESUMO

Aberrant activation of interferon (IFN)-γ signaling plays a key role in several autoimmune skin diseases, including lupus erythematosus, alopecia areata, vitiligo, and lichen planus. Here, we identify fully chemically modified small interfering RNAs (siRNAs) that silence the ligand binding chain of the IFN-γ receptor (IFNGR1), for the modulation of IFN-γ signaling. Conjugating these siRNAs to docosanoic acid (DCA) enables productive delivery to all major skin cell types local to the injection site, with a single dose of injection supporting effective IFNGR1 protein reduction for at least 1 month in mice. In an ex vivo model of IFN-γ signaling, DCA-siRNA efficiently inhibits the induction of IFN-γ-inducible chemokines, CXCL9 and CXCL10, in skin biopsies from the injection site. Our data demonstrate that DCA-siRNAs can be engineered for functional gene silencing in skin and establish a path toward siRNA treatment of autoimmune skin diseases.


Assuntos
Quimiocina CXCL10 , Dermatopatias , Animais , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Interferon gama/metabolismo , Camundongos , Interferência de RNA , RNA Interferente Pequeno/genética
17.
Plant Cell Rep ; 42(11): 1833-1836, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37642675

RESUMO

KEY MESSAGE: The extensive application of CRISPR in cotton was limited due to the labor-intensive transformation process. Thus, we here established a convenient method of CRISPR in cotton by CLCrV-mediated sgRNA delivery.

18.
Cell Mol Life Sci ; 79(10): 523, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36121491

RESUMO

Intestinal stem cells (ISCs) decode and coordinate various types of nutritional information from the diet to support the crypt-villus axis architecture, but how specific dietary molecules affect intestinal epithelial homeostasis remains unclear. In the current study, L-glutamate (Glu) supplementation in either a nitrogen-free diet (NFD) or a corn-soybean meal diet (CSMD) stimulated gut growth and ISC expansion in weaned piglets. Quantitative proteomics screening identified the canonical Wnt signalling pathway as a central regulator of intestinal epithelial development and ISC activity in vivo. Importantly, the Wnt transmembrane receptor Frizzled7 (FZD7) was upregulated in response to dietary Glu patterns, and its perturbations in intestinal organoids (IOs) treated with a specific inhibitor and in FZD7-KO IPEC-J2 cells disrupted the link between Glu inputs and ß-catenin signalling and a subsequent reduction in cell viability. Furthermore, co-localization, coimmunoprecipitation (Co-IP), isothermal titration calorimetry (ITC), and microscale thermophoresis (MST) revealed that Glu served as a signalling molecule directly bound to FZD7. We propose that FZD7-mediated integration of the extracellular Glu signal controls ISC proliferation and differentiation, which provides new insights into the crosstalk of nutrients and ISCs.


Assuntos
Ácido Glutâmico , beta Catenina , Animais , Proliferação de Células , Ácido Glutâmico/metabolismo , Células-Tronco , Suínos , Via de Sinalização Wnt , beta Catenina/metabolismo
19.
Mediators Inflamm ; 2023: 5831858, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022688

RESUMO

Background: The systemic immune-inflammation index (SII) is used as an indicator of prognosis for a wide range of diseases. Thyroid function has been found to be strongly associated with inflammation. The purpose of this investigation was to analyze the correlation between SII and various thyroid functions. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. The association between SII and thyroid function was analyzed using weighted univariate and multivariate linear regression analyses. Subgroup analyses, interaction tests, and weighted restricted cubic spline (RCS) regression analyses were also employed to test this correlation. Results: Of the 6,875 participants (age ≥ 20 years), the mean age was 46.87 ± 0.40 years. The adjusted model showed that lnSII was negatively correlated with FT3 (ß = -0.0559, 95% CI -0.1060 to -0.0059,) and FT3/FT4 (ß = -0.0920, 95% CI -0.1667 to -0.0173,). There was a positive correlation between lnSII and TT4 (ß = 0.1499, 95% CI 0.0722-0.2276,). In subgroup analyses, lnSII still independently affected a wide range of thyroid functions. Weighted RCS analysis showed a nonlinear relationship between FT3 and lnSII. Conclusion: Close relationships exist between SII and a variety of thyroid functions. SII can be used as an indicator to predict thyroid dysfunction. Control of inflammatory activity may be a protective measure against thyroid dysfunction. More large-scale prospective studies are necessary to further explore the correlation between SII and thyroid function and the role of obesity in this.


Assuntos
Inflamação , Glândula Tireoide , Humanos , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Inquéritos Nutricionais , Estudos Prospectivos , Modelos Lineares
20.
J Shoulder Elbow Surg ; 32(1): 192-200, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36167290

RESUMO

BACKGROUND: Previous researchers used transverse fractures centered over the midpoint of the clavicle as the diaphyseal clavicular fracture models. However, as a result of shear stress concentration in sigmoid-shaped structures, most diaphyseal clavicular fractures have coronal fracture edges and are located distal to the midpoint. The purpose of this study was to quantify the morphology and utilize these parameters to establish clinically relevant fracture models. METHODS: The computed tomographic DICOM data of 100 consecutive patients were included. We investigated the morphologic characteristics of the fracture edges after virtual fracture reduction. The fracture orientation was determined based on the normal vectors of the best-fit plane of the fracture edges. The fracture location was measured by the extreme points of the edges. The fracture configuration was evaluated using fracture maps. RESULTS: There were 28 simple, 43 wedge, and 29 multifragmentary types. Coronal oriented fracture edges accounted for more than 70% of the simple, wedge, and multifragmentary types. The most proximal point of the proximal edge was located at 46.7% (42.0%-56.5%), 47.6% (42.5%-50.1%), and 46.3% (42.0%-49.3%) of the endpoint line in the simple, wedge, and multifragmentary types, respectively (P = .548). The most distal point of the distal edge was located at 72.2% (68.4%-75.0%), 73.2% (69.5%-76.9%), and 74.0% (69.6%-77.1%) of the endpoint line (P = .353). The longest proximal main fragments occurred in the simple types at 71.9% (66.3%-75.4%) of the endpoint line (P < .001), and the shortest distal main fragments occurred in the multifragmentary types at 55.8% (49.8%-59.3%) of the endpoint line (P = .001). The heatmaps showed a high concentration of anteriorly distributed wedge fragments (88%; n = 38/43) and coronally distributed multifragmentary fragments (62%; n = 18/29). CONCLUSIONS: We showed that typical diaphyseal clavicular fractures have coronal fracture edges and are located within the distal half of the diaphyseal segment. The fractured fragments were initiated anteriorly in the wedge types and then propagated coronally in the multifragmentary types. The features of these fracture edges could be useful in designing osteotomy models and provide different perspectives of anterior and superior plating techniques.


Assuntos
Clavícula , Fraturas Ósseas , Humanos , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Diáfises/diagnóstico por imagem , Fixação Interna de Fraturas/métodos , Osteotomia
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