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Assessing programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer (NSCLC), particularly in metastatic cases, remains challenging. In this study, surface plasmon resonance (SPR) analysis and [68Ga]Ga-DOTA-WL12 micro-PET/CT imaging are performed. [68Ga]Ga-DOTA-WL12 PET/CT and [18F]FDG PET/CT are performed on a cohort of 20 patients with NSCLC. Semi-quantitative assessments include SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and target-to-background ratio (TBR). DOTA-WL12 exhibits robust PD-L1 binding with a KD value of 0.2 nM. Subsequent human studies reveal significant correlations between PD-L1 expression and the [68Ga]Ga-DOTA-WL12 SUVmax in primary and metastatic lesions, surpassing the [18F]FDG results (r = 0.8889, p <0.0001 vs r = 0.0469, p = 0.8127). Notably, [68Ga]Ga-DOTA-WL12 imaging discerned SUVmax and TBR differences between PD-L1 TPS ≤1% and PD-L1 TPS > 1% groups (p all <0.001). In an NSCLC patient with brain metastases, [68Ga]Ga-DOTA-WL12 shows a SUVmean of 0.04 in the brain background, with TBR values of 17 and 23, underscoring its potential for detecting brain metastases. The study provides initial evidence for the clinical utility of [68Ga]Ga-DOTA-WL12 PET/CT for lesion detection, immunotherapy selection, and therapeutic efficacy evaluation in PD-L1-expressing NSCLC, demonstrating its potential as a valuable tool in NSCLC research and management.
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BACKGROUND: Acute ischemic stroke (AIS) is the most common type of stroke in clinical practice, and individuals with stroke are more prone to psychological disorders than healthy individuals. This study aims to explore the incidence of anxiety and depression and related influencing factors in individuals with AIS. METHODS: In brief, 680 individuals with AIS admitted to Chun'an County First People's Hospital from January 2021 to January 2023 were selected as the research subjects, and their clinical data were retrospectively analyzed. All patients were evaluated with the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) to observe the occurrence of anxiety and depression, and single-factor and multi-factor logistic regression were used to analyze the influencing factors of anxiety and depression. RESULTS: Among the 680 individuals with AIS, there were 63 cases of mild anxiety (9.26%), 25 cases of moderate anxiety (3.68%), and 8 cases of severe anxiety (1.18%), with a total of 96 cases (14.12%) with anxiety symptoms. Additionally, there were 74 cases of mild depression (10.88%), 28 cases of moderate depression (4.12%), and 10 cases of severe depression (1.47%), with a total of 112 cases with depression (16.47%). The results of univariate analysis showed that there was a weak correlation between age, body mass index, disease duration, marital status, and the development of anxiety and depression in individuals with AIS (p > 0.05). Educational level, underlying diseases, family income, and place of residence were found to influence the development of anxiety and depression in individuals with AIS (p < 0.05). The results of multivariate logistic regression analysis showed that educational level (no higher education), underlying diseases (with), family income (<50,000 yuan/year, the average exchange rate of RMB to USD was 6.7261), and place of residence (rural area) were influencing factors for the development of anxiety and depression in individuals with AIS (p < 0.05). CONCLUSION: Depression and anxiety are common psychological disorders in patients with AIS. The level of education (no higher education), underlying diseases (with), family income (<50,000 yuan/year), and place of residence (rural area) were risk factors that may lead to anxiety and depression in individuals with AIS. For those with risk factors for anxiety and depression, reasonable intervention should be continually provided to guide early disease prediction and treatment of anxiety and depression in individuals with AIS.
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Ansiedad , Depresión , Accidente Cerebrovascular Isquémico , Humanos , Estudios Retrospectivos , Masculino , Femenino , Depresión/epidemiología , Ansiedad/epidemiología , Incidencia , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/psicología , Accidente Cerebrovascular Isquémico/complicaciones , Anciano , Factores de Riesgo , Adulto , China/epidemiologíaRESUMEN
Knee varus (KV) deformity leads to abnormal forces in the different compartments of the joint cavity and abnormal mechanical loading thus leading to knee osteoarthritis (KOA). This study used computer-aided design to create 3-dimensional simulation models of KOA with varying varus angles to analyze stress distribution within the knee joint cavity using finite element analysis for different varus KOA models and to compare intra-articular loads among these models. Additionally, we developed a cartilage loading model of static KV deformity to correlate with dynamic clinical cases of cartilage injury. Different KV angle models were accurately simulated with computer-aided design, and the KV angles were divided into (0°, 3°, 6°, 9°, 12°, 15°, and 18°) 7 knee models, and then processed with finite element software, and the Von-Mises stress distribution and peak values of the cartilage of the femoral condyles, medial tibial plateau, and lateral plateau were obtained by simulating the human body weight in axial loading while performing the static extension position. Finally, intraoperative endoscopy visualization of cartilage injuries in clinical cases corresponding to KV deformity subgroups was combined to find cartilage loading and injury correlations. With increasing varus angle, there was a significant increase in lower limb mechanical axial inward excursion and peak Von-Mises stress in the medial interstitial compartment. Analysis of patients' clinical data demonstrated a significant correlation between varus deformity angle and cartilage damage in the knee, medial plateau, and patellofemoral intercompartment. Larger varus deformity angles could be associated with higher medial cartilage stress loads and increased cartilage damage in the corresponding peak stress area. When the varus angle exceeds 6°, there is an increased risk of cartilage damage, emphasizing the importance of early surgical correction to prevent further deformity and restore knee function.
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Cartílago Articular , Análisis de Elementos Finitos , Articulación de la Rodilla , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/cirugía , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Articulación de la Rodilla/fisiopatología , Masculino , Soporte de Peso/fisiología , Fenómenos Biomecánicos , Persona de Mediana Edad , Estrés Mecánico , Femenino , Simulación por Computador , AncianoRESUMEN
Rice blast, caused by Magnaporthe oryzae (M. oryzae), is one of the most common and damaging diseases of rice that limits rice yield and quality. The mediator complex plays a vital role in promoting transcription by bridging specific transcription factors and RNA polymerase II. Here, we show that the rice mediator subunit OsMED16 is essential for full induction of the diterpenoid phytoalexin biosynthesis genes and resistance to the ascomycetous fungus M. oryzae. Mutants of Osmed16 show reduced expression of the DP biosynthesis genes and are markedly more susceptible to M. oryzae, while transgenic plants overexpressing OsMED16 increased the expression of the DP biosynthesis genes and significantly enhanced resistance to M. oryzae. Interestingly, OsMED16 is physically associated with the WRKY family transcription factor OsWRKY45, which interacts with the phytoalexin synthesis key regulator transcription factor OsWRKY62. Further, OsMED16-OsWRKY45-OsWRKY62 complex could bind to the promoter regions of phytoalexin synthesis-related genes and activate their gene expression. Our results show that OsMED16 may enhance rice tolerance to M. oryzae via directly manipulating phytoalexin de novo biosynthesis.
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BACKGROUND: The programmed cell death protein-1 (PD-1)/programmed death receptor ligand 1 (PD-L1) axis critically facilitates cancer cells' immune evasion. Antibody therapeutics targeting the PD-1/PD-L1 axis have shown remarkable efficacy in various tumors. Immuno-positron emission tomography (ImmunoPET) imaging of PD-L1 expression may help reshape solid tumors' immunotherapy landscape. METHODS: By immunizing an alpaca with recombinant human PD-L1, three clones of the variable domain of the heavy chain of heavy-chain only antibody (VHH) were screened, and RW102 with high binding affinity was selected for further studies. ABDRW102, a VHH derivative, was further engineered by fusing RW102 with the albumin binder ABD035. Based on the two targeting vectors, four PD-L1-specific tracers ([68Ga]Ga-NOTA-RW102, [68Ga]Ga-NOTA-ABDRW102, [64Cu]Cu-NOTA-ABDRW102, and [89Zr]Zr-DFO-ABDRW102) with different circulation times were developed. The diagnostic efficacies were thoroughly evaluated in preclinical solid tumor models, followed by a first-in-human translational investigation of [68Ga]Ga-NOTA-RW102 in patients with non-small cell lung cancer (NSCLC). RESULTS: While RW102 has a high binding affinity to PD-L1 with an excellent KD value of 15.29 pM, ABDRW102 simultaneously binds to human PD-L1 and human serum albumin with an excellent KD value of 3.71 pM and 3.38 pM, respectively. Radiotracers derived from RW102 and ABDRW102 have different in vivo circulation times. In preclinical studies, [68Ga]Ga-NOTA-RW102 immunoPET imaging allowed same-day annotation of differential PD-L1 expression with specificity, while [64Cu]Cu-NOTA-ABDRW102 and [89Zr]Zr-DFO-ABDRW102 enabled longitudinal visualization of PD-L1. More importantly, a pilot clinical trial shows the safety and diagnostic value of [68Ga]Ga-NOTA-RW102 immunoPET imaging in patients with NSCLCs and its potential to predict immune-related adverse effects following PD-L1-targeted immunotherapies. CONCLUSIONS: We developed and validated a series of PD-L1-targeted tracers. Initial preclinical and clinical evidence indicates that immunoPET imaging with [68Ga]Ga-NOTA-RW102 holds promise in visualizing differential PD-L1 expression, selecting patients for PD-L1-targeted immunotherapies, and monitoring immune-related adverse effects in patients receiving PD-L1-targeted treatments. TRIAL REGISTRATION NUMBER: NCT06165874.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Compuestos Heterocíclicos con 1 Anillo , Neoplasias Pulmonares , Anticuerpos de Dominio Único , Humanos , Antígeno B7-H1/efectos de los fármacos , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Radioisótopos de Galio , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Receptor de Muerte Celular Programada 1 , Anticuerpos de Dominio Único/farmacología , Anticuerpos de Dominio Único/uso terapéuticoRESUMEN
Accurately predicting and selecting patients who can benefit from targeted or immunotherapy is crucial for precision therapy. Trophoblast cell surface antigen 2 (Trop2) has been extensively investigated as a pan-cancer biomarker expressed in various tumours and plays a crucial role in tumorigenesis through multiple signalling pathways. Our laboratory successfully developed two 68Ga-labelled nanobody tracers that can rapidly and specifically target Trop2. Of the two tracers, [68Ga]Ga-NOTA-T4, demonstrated excellent pharmacokinetics in preclinical mouse models and a beagle dog. Moreover, [68Ga]Ga-NOTA-T4 immuno-positron emission tomography (immunoPET) allowed noninvasive visualisation of Trop2 heterogeneous and differential expression in preclinical solid tumour models and ten patients with solid tumours. [68Ga]Ga-NOTA-T4 immunoPET could facilitate clinical decision-making through patient stratification and response monitoring during Trop2-targeted therapies.
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Antígenos de Neoplasias , Moléculas de Adhesión Celular , Neoplasias , Tomografía de Emisión de Positrones , Animales , Perros , Femenino , Ratones , Antígenos de Neoplasias/metabolismo , Antígenos de Neoplasias/inmunología , Moléculas de Adhesión Celular/metabolismo , Neoplasias/diagnóstico por imagen , Neoplasias/inmunología , Tomografía de Emisión de Positrones/métodos , Anticuerpos de Dominio Único/inmunologíaRESUMEN
PURPOSE: The cluster of differentiation (CD70) is a potential biomarker of clear cell renal cell carcinoma (ccRCC). This study aims to develop CD70-targeted immuno-positron emission tomography/computed tomography (immunoPET/CT) imaging tracers and explore the diagnostic value in preclinical studies and the potential value in detecting metastases in ccRCC patients. METHODS: Four novel CD70-specific single-domain antibodies (sdAbs) were produced and labelled with 18F by the aluminium fluoride restrained complexing agent (AlF-RESCA) method to develop radiotracers. The visualisation properties of the tracers were evaluated in a subcutaneous ccRCC patient-derived xenograft (PDX) model. In a registered prospective clinical trial (NCT06148220), six patients with pathologically confirmed RCC were included and underwent immunoPET/CT examination exploiting one of the developed tracers (i.e., [18F]RCCB6). RESULTS: We engineered four sdAbs (His-tagged RCCB3 and RCCB6, His-tag-free RB3 and RB6) specifically targeting recombinant human CD70 without cross-reactivity to murine CD70. ImmunoPET/CT imaging with [18F]RCCB3 and [18F]RCCB6 demonstrated a high tumour-to-background ratio in a subcutaneous ccRCC PDX model, with the latter showing better diagnostic potential supported by higher tumour uptake and lower bone accumulation. In comparison, [18F]RB6, developed by sequence optimisation, has significantly lower kidney accumulation than that of [18F]RCCB6. In a pilot translational study, [18F]RCCB6 immunoPET/CT displayed ccRCC metastases in multiple patients and demonstrated improved imaging contrast and diagnostic value than 18F-FDG PET/CT in a patient with ccRCC. CONCLUSION: The work successfully developed a series of CD70-targeted immunoPET/CT imaging tracers. Of them, [18F]RCCB6 clearly and specifically identified inoculated ccRCCs in preclinical studies. Clinical translation of [18F]RCCB6 suggests potential for identifying recurrence and/or metastasis in ccRCC patients.
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Carcinoma de Células Renales , Neoplasias Renales , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Carcinoma de Células Renales/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias Renales/diagnóstico por imagen , Femenino , Masculino , Radioisótopos de Flúor/química , Animales , Ratones , Persona de Mediana Edad , Anticuerpos de Dominio Único , Anciano , Línea Celular Tumoral , Distribución TisularRESUMEN
The extensive accumulation of polyethylene terephthalate (PET) has become a critical environmental issue. PET hydrolases can break down PET into its building blocks. Recently, we identified a glacial PET hydrolase GlacPETase sharing less than 31% amino acid identity with any known PET hydrolases. In this study, the crystal structure of GlacPETase was determined at 1.8 Å resolution, revealing unique structural features including a distinctive N-terminal disulfide bond and a specific salt bridge network. Site-directed mutagenesis demonstrated that the disruption of the N-terminal disulfide bond did not reduce GlacPETase's thermostability or its catalytic activity on PET. However, mutations in the salt bridges resulted in changes in melting temperature ranging from -8°C to +2°C and the activity on PET ranging from 17.5% to 145.5% compared to the wild type. Molecular dynamics simulations revealed that these salt bridges stabilized the GlacPETase's structure by maintaining their surrounding structure. Phylogenetic analysis indicated that GlacPETase represented a distinct branch within PET hydrolases-like proteins, with the salt bridges and disulfide bonds in this branch being relatively conserved. This research contributed to the improvement of our comprehension of the structural mechanisms that dictate the thermostability of PET hydrolases, highlighting the diverse characteristics and adaptability observed within PET hydrolases.IMPORTANCEThe pervasive problem of polyethylene terephthalate (PET) pollution in various terrestrial and marine environments is widely acknowledged and continues to escalate. PET hydrolases, such as GlacPETase in this study, offered a solution for breaking down PET. Its unique origin and less than 31% identity with any known PET hydrolases have driven us to resolve its structure. Here, we report the correlation between its unique structure and biochemical properties, focusing on an N-terminal disulfide bond and specific salt bridges. Through site-directed mutagenesis experiments and molecular dynamics simulations, the roles of the N-terminal disulfide bond and salt bridges were elucidated in GlacPETase. This research enhanced our understanding of the role of salt bridges in the thermostability of PET hydrolases, providing a valuable reference for the future engineering of PET hydrolases.
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Hidrolasas , Tereftalatos Polietilenos , Tereftalatos Polietilenos/metabolismo , Filogenia , Estabilidad de Enzimas , Hidrolasas/metabolismo , Disulfuros , TemperaturaRESUMEN
The assembly line biosynthesis of the powerful anticancer-antiviral didemnin cyclic peptides is proposed to follow a prodrug release mechanism in Tristella bacteria. This strategy commences with the formation of N-terminal prodrug scaffolds and culminates in their cleavage during the cellular export of the mature products. In this study, a comprehensive exploration of the genetic and biochemical aspects of the enzymes responsible for both the assembly and cleavage of the acylated peptide prodrug scaffolds is provided. This process involves the assembly of N-acyl-polyglutamine moieties orchestrated by the nonribosomal peptide synthetase DidA and the cleavage of these components at the post-assembly stage by DidK, a transmembrane CAAX hydrolase homolog. The findings not only shed light on the complex prodrug mechanism that underlies the synthesis and secretion of didemnin compounds but also offer novel insights into the expanded role of CAAX hydrolases in microbes. Furthermore, this knowledge can be leveraged for the strategic design of genome mining approaches aimed at discovering new bioactive natural products that employ similar prodrug biochemical strategies.
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Depsipéptidos , Profármacos , Péptido Hidrolasas , Endopeptidasas , Profármacos/farmacologíaRESUMEN
Bacteria can be programmed to create engineered living materials (ELMs) with self-healing and evolvable functionalities. However, further development of ELMs is greatly hampered by the lack of engineerable nonpathogenic chassis and corresponding programmable endogenous biopolymers. Here, we describe a technological workflow for facilitating ELMs design by rationally integrating bioinformatics, structural biology and synthetic biology technologies. We first develop bioinformatics software, termed Bacteria Biopolymer Sniffer (BBSniffer), that allows fast mining of biopolymers and biopolymer-producing bacteria of interest. As a proof-of-principle study, using existing pathogenic pilus as input, we identify the covalently linked pili (CLP) biosynthetic gene cluster in the industrial workhorse Corynebacterium glutamicum. Genetic manipulation and structural characterization reveal the molecular mechanism of the CLP assembly, ultimately enabling a type of programmable pili for ELM design. Finally, engineering of the CLP-enabled living materials transforms cellulosic biomass into lycopene by coupling the extracellular and intracellular bioconversion ability.
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Bacterias , Ingeniería Metabólica , Flujo de Trabajo , Licopeno , BiopolímerosRESUMEN
BACKGROUND: To what extent traditional Chinese medicine (TCM) combined with mifepristone and misoprostol is beneficial for improving the complete abortion rate and duration of vaginal bleeding has been a subject of debate in the field of medical abortion. OBJECTIVE: To assess the evidence regarding the complete abortion rate and duration of vaginal bleeding of medical abortion assisted by different kinds of TCM. SEARCH STRATEGY: We searched electronic databases such as PubMed, Web of Science and Cochrane Library database, China National Knowledge Internet, Wan fang Database, VIP Database, and China Biology Medicine disc from 2000 to February 15, 2023. SELECTION CRITERIA: The control group was medical abortion with mifepristone and misoprostol, and the experimental group was medical abortion assisted by TCM. DATA COLLECTION AND ANALYSIS: Major data extraction included sample size, age, medicine used for abortion, outcome measures. RevMan 5.3 and Stata 15.1 software were used to assess the literature quality and perform network meta-analysis, respectively. MAIN RESULTS: A total of 73 randomized controlled trials (RCTs) with 11 683 patients and nine kinds of TCM were included in this study. Compared with mifepristone and misoprostol, eight kinds of TCM had statistical significance in improving the complete abortion rate. The effect value of Sancao decoction was 5.86 (95% confidence interval [CI] 2.53-13.58). Seven kinds of TCM shortened the duration of vaginal bleeding. The effect value of comfrey and trichosanthin decoction was -8.75 (95% CI -10.86 to -6.64). CONCLUSIONS: This network meta-analysis showed that Lenge Zhumo decoction and Sancao decoction could have a large beneficial effect on complete abortion rate in medical abortion during early pregnancy, and comfrey and trichosanthin decoction could be the best TCM for shortening the duration of vaginal bleeding.
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ABSTRACT: Bacille Calmette-Guérin (BCG) vaccine is designed to provide protection against tuberculosis (TB). However, numerous epidemiological, clinical, and immunological studies have shown that BCG vaccination affects neonatal and infant mortality, which may be related to the reduction of TB-unrelated infections and diseases by BCG vaccine. We aimed to discuss the off-target effects of BCG vaccine on un-TB infections and diseases, as well as the potential mechanism and influencing factors. Literature was retrieved mainly from PubMed using medical subject headings "BCG, variations, and non-specific, heterologous or off-target". Studies have showed that BCG vaccination can prevent various heterologous infections, including respiratory tract infections, leprosy, and malaria, treat viral infections including human papillomavirus and herpes simplex virus infection as immunotherapy, and improve the immune responses as vaccine adjuvant. Besides, BCG vaccine can reduce the recurrence rate of non-muscle-invasive bladder cancer, and may provide protection against autoimmune diseases. These off-target effects of BCG vaccine are thought to be achieved by modulating heterologous lymphocyte responses or inducing trained immunity, which were found to be sex-differentiated and affected by the BCG vaccine strains, sequence or time of vaccination.
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OBJECTIVE: Oblique lateral interbody fusion (OLIF) surgery is a minimally invasive spinal surgery technique that has become increasingly popular in recent years. The primary objective of the current study was to design a minimally invasive expandable fusion device that can reduce iatrogenic nerve damage and minimize endplate damage during OLIF surgery, while restoring intervertebral height and alignment. The second objective was to use finite element analysis to evaluate the biomechanical stability of the newly designed expandable fusion device after implantation into the intervertebral space. METHODS: A new bidirectional expandable cage was designed in this study. A finite element model (FEM) of L3-L5 lumbar segment was modified to simulate decompression and fusion. The modified FEMs were constructed in the following cases: intact model, bidirectional expandable cage (alone, with unilateral pedicle screws [UPSs], and with bilateral pedicle screws [BPSs]) model, conventional OLIF cage (alone, with UPSs, and with BPSs) model. To simulate physiological loadings, the models were subjected to a follower compressive pre-load of 400 N, in addition to 8.0 Nm of flexion, extension, lateral bending, and axial rotation moments. RESULT: All modified FEMs exhibited a significant reduction in motion at L3-L5 compared to the intact model. Among the fusion models, the bidirectional expandable cage (BEC) with BPS model displayed the highest stiffness and demonstrated a reduced range of motion (48.5%-75.7%). Additionally, the peak stress on the endplate in the conventional OLIF cage (Conv-OLIF) model was generally lower than that in the BEC models. The cage in the BEC ALONE model exhibited the highest stress (93.87-176.3 MPa) on the endplate in most motion modes, while the cage in the Conv-OLIF+BPS model had the lowest stress (16.67-30.58 MPa) on the endplate in most motion modes. The maximum stress on the fixation in the BEC fusion models was generally lower than that in the Conv-OLIF fusion group under the same loading conditions. The OLIF ALONE model had the lowest stress on the adjacent disc, while the stress level in the BEC ALONE model was very close to it. CONCLUSIONS: The BEC implanted models had higher stiffness, and more proper stress distribution on the posterior fixation was comparable to that of the Conv-OLIF models. However, the endplate stress peaks and cage stress peaks of the BEC models were slightly higher than those of the Conv-OLIF models, though still within a clinically acceptable range. Taking into account both biomechanical and clinical perspectives, BEC-assisted unilateral pedicle screw fixation meet clinical demand and may serve as a viable alternative to Conv-OLIF fusion.
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Tornillos Pediculares , Fusión Vertebral , Humanos , Vértebras Lumbares/cirugía , Vértebras Lumbares/fisiología , Fusión Vertebral/métodos , Fenómenos Biomecánicos , Rango del Movimiento Articular/fisiología , Análisis de Elementos FinitosRESUMEN
Electrically generated spin-orbit torque (SOT) has emerged as a powerful pathway to control magnetization for spintronic applications including memory, logic, and neurocomputing. However, the requirement of external magnetic fields, together with the ultrahigh current density, is the main obstacle for practical SOT devices. In this paper, we report that the field-free SOT-driven magnetization switching can be successfully realized by interfacial ion absorption in perpendicular Ta/CoFeB/MgO multilayers. Besides, the tunable SOT efficiency exhibits a strong dependence on interfacial Ti insertion thicknesses. Polarized neutron reflection measurements demonstrate the existence of canted magnetization with Ti inserted, which leads to deterministic magnetization switching. In addition, interfacial characterization and first-principles calculations reveal that B absorption by the Ti layer is the main cause behind the enhanced interfacial transparency, which determines the tunable SOT efficiency. Our findings highlight an attractive scheme to a purely electric control spin configuration, enabling innovative designs for SOT-based spintronics via interfacial engineering.
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Mediator, a universal eukaryotic coactivator, is a multiprotein complex to transduce information from the DNA-bound transcription factors to the RNA polymerase II transcriptional machinery. In this study, the biofunctions of a rice mediator subunit OsMED16 in leaf development and blast resistance were characterized. OsMED16 encodes a putative protein of 1170 amino acids, which is 393 bp shorted than the version in Rice Genome Annotation Project databases. Overexpression of OsMED16 plants exhibited wider leaves with larger and more numerous cells in lateral axis, and enhanced resistance to M. oryzae with hyperaccumulated salicylic acid. Further analysis revealed that OsMED16 interacts with OsE2Fa in nuclei, and the complex could directly regulate the transcriptional levels of several genes involved in cell cycle regulation and SA mediated blast resistance, such as OsCC52A1, OsCDKA1, OsCDKB2;2, OsICS1 and OsWRKY45. Altogether, this study proved that OsMED16 is a positive regulator of rice leaf development and blast resistance, and providing new insights into the crosstalk between cell cycle regulation and immunity.
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Magnaporthe , Oryza , Oryza/metabolismo , Magnaporthe/metabolismo , Regulación de la Expresión Génica de las Plantas , Complejo Mediador/genética , Complejo Mediador/metabolismo , Proteínas de Plantas/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genéticaRESUMEN
RATIONALE: In the field of separation science, ion mobility spectrometry (IMS) plays an important role as an analytical tool. However, the lack of sufficient structural resolution is a common problem in qualitative and quantitative analysis using IMS. A method is needed to solve the problem of overlapping peaks caused by insufficient resolution. METHODS: The method uses multiple strategies to more effectively use population information to balance exploration and exploitation capabilities, prevent local optimization, accurately resolve overlapping peaks, quickly obtain optimal spectral peak model coefficients, and accurately identify compounds. RESULTS: Multistrategy JAYA algorithm's (MSJAYA) performance is compared with improved particle swarm optimization (IPSO), dynamic inertia weight particle swarm optimization (DIWPSO), and multiobjective dynamic teaching-learning-based optimization (MDTLBO). The analysis shows that MSJAYA's maximum separation error is within 0.6%, a level of accuracy not guaranteed by the other algorithms. In addition, the separation error fluctuates within a much smaller range, demonstrating MSJAYA's superior robustness. CONCLUSIONS: Compared with other overlapping peak separation algorithms, MSJAYA is more applicable because no special parameters are used. The method allows fast deconvolution analysis of strong overlapping peaks with multiple components, which greatly improves the resolution of IMS.
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BACKGROUND: Knee osteoarthritis (OA) is commonly combined with the presentation of a coronal deformity of the knee. The bony origin of the knee varus deformity can be classified as tibial origin, femoral origin, or a combination of tibial and femoral causes. Deformities of tibial origin are mostly common clinically, while patients with knee OA with femoral varus deformity are less common. RESEARCH QUESTION: Do hip, knee and ankle kinematics and spatiotemporal parameters differ between patients with knee OA with femoral varus deformity and healthy subjects? METHODS: Twenty-five patients (14 females and 11 males) with knee OA and femoral varus deformity and 20 healthy subjects (12 males and 8 females) as control group were included in this study. The kinematic parameters of the hip-knee-ankle joint and spatiotemporal gait parameters were included in the study. RESULTS: This study found that the step speed and step length of the knee OA with femoral varus (KOAF) group were smaller than those of the control group, while double support period percentage was greater in the KOAF group. Significant differences were found in the maximum knee extension angle, maximum knee flexion angle, knee flexion range of motion, maximum hip flexion angle, maximum hip extension angle, and hip flexion range of motion between the two groups. After comparing the ankle motion between the two groups, significant differences were found in the maximum eversion angle, inversion range of motion, maximum ankle abduction angle, and abduction range of motion. SIGNIFICANCE: Knee OA with femoral varus deformity causes adaptive changes in the kinematic parameters of hip, knee and ankle joints and spatiotemporal gait parameters to alleviate symptoms and maintain normal activity.
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Osteoartritis de la Rodilla , Masculino , Femenino , Humanos , Osteoartritis de la Rodilla/complicaciones , Análisis de la Marcha , Fenómenos Biomecánicos , Articulación de la Rodilla , FémurRESUMEN
BACKGROUND: Garden I femoral neck fractures are nondisplaced femoral neck fractures. Nonoperative treatment and in situ fixation are the preferred treatments. However, the postoperative outcome is not satisfactory and the incidence of complications remains high, which raises doubts about the accuracy of the diagnosis of nondisplaced Garden I fractures. Recently, three-dimensional (3D) reconstruction has been reported as a mature technology for reconstructing the bone structure of patients. We further extended this technique in the measurement of the fracture spatial displacement to verify the accuracy of Garden I femoral neck fractures. METHODS: This was a retrospective study of patients with Garden I femoral neck fractures from January 2013 to December 2018 at our institution, who were included according to specified criteria. A bilateral proximal femur model of each patient was established based on computed tomography (CT) data. The displacement of the deepest portion of the femoral head fovea, the displacement of the center of the femoral head and the rotation of the femoral head were measured in the bilateral model. RESULTS: A total of 102 patients diagnosed with Garden I fractures were included in this study. The cohort included 32 men and 70 women, with an average age of 55.88 ± 15.32 years. In these patients, the average displacement of the deepest portion of the femoral head fovea was 16.43 ± 7.69 mm. The minimum and maximum displacement was 3.58 and 44.32 mm, respectively. The average displacement of the center of the femoral head was 10.39 ± 5.47 mm and ranged from 2.16 to 34.42 mm. The rotational angle was 23.81 ± 10.15 ° and ranged from 3.71 ° to 61.19 °. CONCLUSIONS: Garden I fractures have large spatial displacement and cannot be considered incomplete or nondisplaced fractures. Therefore, we suggest that anatomical reduction should be considered during treatment.