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1.
J Orthop Surg Res ; 19(1): 298, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755648

RESUMO

BACKGROUND: A new classification system for acetabular fractures has been proposed in recent years, which is called the 3-column classification. However, this system does not provide information regarding quadrilateral plate fractures. To address this issue, we utilized three-dimensional (3D) fracture line mapping and heat map to analyze the link between the 3-column classification and quadrilateral plate fractures. METHODS: We collected CT scan data from 177 patients who had been diagnosed with acetabular fractures. Additionally, we utilized a CT scan of a healthy adult to generate a standard acetabular model. We utilized the collected CT data of the fracture to create a 3D model and subsequently reduced it. We then matched each acetabular fracture model with the standard acetabular model and mapped all of the fracture lines to the standard model. 3D fracture lines and heat maps were created by overlapping all fracture lines. Fracture characteristics were then summarized using these maps. RESULTS: This study analyzed a total of 221 acetabular fractures. The most frequently observed fracture type, based on the three-column classification, was A1.2, which corresponds to fractures of the anterior column. In contrast, the least common type of fracture was A4, which represents fractures of the central wall. It was noted that quadrilateral plate fractures were frequently observed in fractures classified as type B and C according to the three-column classification. CONCLUSIONS: Among the three-column classification, the QLP fractures are commonly observed in type B and C. It is important to carefully identify these fractures during the diagnostic process. Therefore, based on the three-column classification, we have amalgamated quadrilateral plate fractures and formulated a classification program for acetabular fractures.


Assuntos
Acetábulo , Fraturas Ósseas , Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Humanos , Acetábulo/lesões , Acetábulo/diagnóstico por imagem , Feminino , Masculino , Adulto , Fraturas Ósseas/classificação , Fraturas Ósseas/diagnóstico por imagem , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Idoso , Adulto Jovem , Idoso de 80 Anos ou mais , Adolescente
2.
J Hazard Mater ; 470: 134180, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38569342

RESUMO

Obtaining suitable adsorbents for selective separation of SO2 from flue gas still remains an important issue. A stable Zr(IV)-MOF (Zr-PTBA) can be conveniently synthesized through the self-assembly of a tetracarboxylic acid ligand (H4L = 4,4',4'',4'''-(1,4-phenylenebis(azanetriyl))tetrabenzoic acid) and ZrCl4 in the presence of trace water. It exhibits a three-dimensional porous structure. The BET surface area is 1112.72 m2/g and the average pore size distribution focus on 5.9, 8.0 and 9.3 Å. Interestingly, Zr-PTBA shows selective adsorption of SO2. The maximum uptake reaches 223.21 cm3/g at ambient condition. While it exhibits lower adsorption uptake of CO2 (30.50 cm3/g) and hardly adsorbs O2 (2.57 cm3/g) and N2 (1.31 cm3/g). Higher IAST selectivities of SO2/CO2 (21.9), SO2/N2 (912.7), SO2/O2 (2269.9) and SO2/CH4 (85.0) have been obtained, which reveal its' excellent gas separation performance. Breakthrough experiment further confirms its application for flue gas deep desulfurization both in dry and humid conditions. Furthermore, the gas adsorption results and mechanisms have also been studied by theoretical calculations.

3.
Orthop Surg ; 16(5): 1196-1206, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38485459

RESUMO

OBJECTIVE: The talus is an important component in the ankle, and its treatment after injury is crucial. However, complications and adverse events due to incomplete traditional classifications may still occur, and these classifications fail to analyze the patterns and distribution of fractures from a three-dimensional perspective. Therefore, in this study, we aimed to analyze the location and distribution of fracture lines in different types of talus fractures using three-dimensional (3D) and heat mapping techniques. Additionally, we aimed to determine the surface area of the talus that can be utilized for different approaches of internal fixation, aiding in the planning of surgical procedures. METHODS: We retrospectively analyzed data from CT scans from 126 patients diagnosed with talus fractures at our two hospitals. We extracted the CT data of a healthy adult and created a standard talus model. We performed 3D reconstruction using patients' CT images and superimposed the fracture model onto the standard model for drawing fracture lines. Subsequently, we converted the fracture lines into a heat map for visualization. Additionally, we measured 20 specimens to determine the boundary for various ligaments attached to the talus. We determined the surface area of the talus available for different surgical approaches by integrating the boundary data with previously reported data on area of exposure. RESULTS: Without considering the displacement distance of the fracture, fracture types were classified as follows, by combining Hawkins and Sneppen classifications: talar neck, 41.3%; posterior talar tubercle, 22.2%; body for the talus and comminuted, 17.5%; lateral talar tubercle, 11.9%; and talar head, 7.1%. We established fracture line and heat maps using this classification. Additionally, we demonstrated the available area for anteromedial, anterolateral, posteromedial, posterolateral, and medial malleolus osteotomy and Chaput osteotomy approaches. CONCLUSION: Fracture line and heat map analyses can aid surgeons in planning a single or combined surgical approach for the reduction and internal fixation of talus fractures. Demonstrating the different surgical approaches can help surgeons choose the most effective technique for individual cases.


Assuntos
Fixação Interna de Fraturas , Fraturas Ósseas , Imageamento Tridimensional , Tálus , Tomografia Computadorizada por Raios X , Humanos , Tálus/lesões , Tálus/cirurgia , Tálus/diagnóstico por imagem , Estudos Retrospectivos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/classificação , Idoso , Adulto Jovem , Adolescente , Fraturas do Tornozelo/cirurgia , Fraturas do Tornozelo/diagnóstico por imagem
4.
Int J Surg ; 110(6): 3888-3899, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38477123

RESUMO

BACKGROUND: Achilles tendon rupture (ATR) is a significant injury that can require surgery and can have the risk of re-rupture even after successful treatment. Consequently, to minimize this risk, it is important to have a thorough understanding of the rehabilitation protocol and the impact of different rehabilitation approaches on preventing re-rupture. MATERIALS AND METHODS: Two independent team members searched several databases (PubMed, EMBASE, Web of Science, Cochrane Library, and CINAHL) to identify randomized controlled trials (RCTs) on operative treatment of ATR. We included articles that covered open or minimally invasive surgery for ATR, with a detailed rehabilitation protocol and reports of re-rupture. The study protocol has been registered at PROSPERO and has been reported in the line with PRISMA Guidelines, Supplemental Digital Content 1, http://links.lww.com/JS9/C85 , Supplemental Digital Content 2, http://links.lww.com/JS9/C86 and assessed using AMSTAR Tool, Supplemental Digital Content 3, http://links.lww.com/JS9/C87 . RESULTS: A total of 43 RCTs were eligible for the meta-analysis, encompassing a combined cohort of 2553 patients. Overall, the postoperative incidence of ATR patients developing re-rupture was 3.15% (95% CI: 2.26-4.17; I2 =44.48%). Early immobilization group patients who had ATR had a 4.07% (95% CI: 1.76-7.27; I2 =51.20%) postoperative incidence of re-rupture; Early immobilization + active range of motion (AROM) group had an incidence of 5.95% (95% CI: 2.91-9.99; I2 =0.00%); Early immobilization + weight-bearing group had an incidence of 3.49% (95% CI: 1.96-5.43; I2 =20.06%); Early weight-bearing + AROM group had an incidence of 3.61% (95% CI: 1.00-7.73; I2 =64.60%); Accelerated rehabilitation (immobilization) group had an incidence of 2.18% (95% CI: 1.11-3.59; I2 =21.56%); Accelerated rehabilitation (non-immobilization) group had a rate of 1.36% (95% CI: 0.12-3.90; I2 =0.00%). Additionally, patients in the immediate AROM group had a postoperative re-rupture incidence of 3.92% (95% CI: 1.76-6.89; I2 =33.24%); Non-immediate AROM group had an incidence of 2.45% (95% CI: 1.25-4.03; I2 =22.09%). CONCLUSIONS: This meta-analysis suggests the use of accelerated rehabilitation intervention in early postoperative rehabilitation of the Achilles tendon. However, for early ankle joint mobilization, it is recommended to apply after one to two weeks of immobilization.


Assuntos
Tendão do Calcâneo , Ensaios Clínicos Controlados Aleatórios como Assunto , Traumatismos dos Tendões , Humanos , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/lesões , Ruptura/cirurgia , Traumatismos dos Tendões/cirurgia , Traumatismos dos Tendões/reabilitação , Incidência , Deambulação Precoce/estatística & dados numéricos
5.
J Foot Ankle Surg ; 63(4): 435-442, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38438102

RESUMO

In recent years, anterior tibiofibular ligament-distal fascicle transfers for anterior talofibular ligament augmentation repair have proposed. However, a comprehensive biomechanical study on the anterior tibiofibular ligament-distal fascicle transfer is still lacking. We are established four distinct groups, namely the normal, the anterior talofibular ligament rupture, the anterior talofibular ligament repair, and the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer. We assessed the anterior drawer test and varus stress test of the ankle in each group. Moreover, we employed the model to simulate and compute the total displacement and von-Mises stress of the talus cartilage at varying gait phases, including foot strike, tibia vertical, and toe-off phases. The results of the anterior drawer test and varus stress test revealed that the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group exhibited greater closeness to the normal group. Regarding von-Mises stress in cartilage, the three gait instants had higher values in the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group than the other groups. Nevertheless, regarding total displacement, the toe-off phases exhibited higher values in the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group than the other groups. Using ATiFL-DF transfer to augment ATFL repair is a potential feasible procedure. However, this procedure could potentially compromise the anterior tibiofibular ligament's contribution to the dynamic stability of the ankle. Therefore, we recommend conducting further in-depth research to ensure the suitability and success of this technique in a clinical environment.


Assuntos
Articulação do Tornozelo , Análise de Elementos Finitos , Instabilidade Articular , Ligamentos Laterais do Tornozelo , Humanos , Ligamentos Laterais do Tornozelo/cirurgia , Instabilidade Articular/cirurgia , Instabilidade Articular/fisiopatologia , Articulação do Tornozelo/cirurgia , Articulação do Tornozelo/fisiopatologia , Fenômenos Biomecânicos , Adulto , Masculino , Doença Crônica
6.
Front Pharmacol ; 15: 1257253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370471

RESUMO

PARP1 is one of six enzymes required for the highly error-prone DNA repair pathway microhomology-mediated end joining (MMEJ) and needs to be inhibited when over-expressed. In order to study the PARP1 inhibitory effect of fused tetracyclic or pentacyclic dihydrodiazepinoindolone derivatives (FTPDDs) by quantitative structure-activity relationship technique, six models were established by four kinds of methods, heuristic method, gene expression programming, random forester, and support vector regression with single, double, and triple kernel function respectively. The single, double, and triple kernel functions were RBF kernel function, the integration of RBF and polynomial kernel functions, and the integration of RBF, polynomial, and linear kernel functions respectively. The problem of multi-parameter optimization introduced in the support vector regression model was solved by the particle swarm optimization algorithm. Among the models, the model established by support vector regression with triple kernel function, in which the optimal R 2 and RMSE of training set and test set were 0.9353, 0.9348 and 0.0157, 0.0288, and R2 cv of training set and test set were 0.9090 and 0.8971, shows the strongest prediction ability and robustness. The method of support vector regression with triple kernel function is a great promotion in the field of quantitative structure-activity relationship, which will contribute a lot to designing and screening new drug molecules. The information contained in the model can provide important factors that guide drug design. Based on these factors, six new FTPDDs have been designed. Using molecular docking experiments to determine the properties of new derivatives, the new drug was ultimately successfully designed.

8.
Talanta ; 271: 125719, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38281429

RESUMO

The design of surface ligands is crucial for ligand-protected gold nanoparticles (AuNPs). Herein, following the principle of green synthesis, environmentally friendly gold nanoparticles (AuNPs@His@CC, AuHC) were fabricated based on dual ligands of histidine and carboxylated chitosan. AuHC showed the advantages of low toxicity, good photoluminescent stability and ideal biocompatibility. Compared with single histidine-coated gold nanoclusters (AuNCs@His, AuH), AuHC presented enhanced fluorescence attributed to the addition of chitosan. The blue-emitting AuHC has a unique response to Fe3+ with detection limits as low as 9.51 nM. Interestingly, the quenched fluorescence of AuHC-Fe3+ system could be restored through the introduction of PPi with a detection limit of 10.6 µM. So an "on-off-on" fluorescence sensing platform was achieved. Apart from good optical properties and sensing, the designed AuHC demonstrated outstanding photothermal conversion efficiency (27.8 %), which made it ideal material for thermal ablation of tumor. To be specific, after laser irradiation (660 nm, 0.78 W cm-2, 10 min) of AuHC, the survival rate of HeLa cells as a tumor cell model decreased to 12.7 %, indicating that AuHC has a significant tumor inhibition effect in vitro. Besides, AuHC also could be a befitting candidate for overcoming drug-resistant tumor cells such as MCF-7/ADR cells. Notably, AuHC can markedly ablate solid tumors in 4T1 tumor-bearing mice after laser irradiation (660 nm, 0.78 W cm-2, 10 min). Hence this work provides insight into the design of multifunctional AuNPs platform for simultaneously integrating the ion sensing and photothermal therapy of cancer.


Assuntos
Quitosana , Nanopartículas Metálicas , Humanos , Animais , Camundongos , Terapia Fototérmica , Ouro , Fluorescência , Células HeLa , Histidina
9.
Quant Imaging Med Surg ; 13(12): 7765-7776, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38106299

RESUMO

Background: Florbetapir positron emission tomography (AV45 PET) is a widely employed modality for detecting cerebral amyloid-ß (Aß) deposition. However, in clinical settings, patients with cognitive impairment are frequently unable to sustain adequate stillness during the scanning procedure. Therefore, we aimed to investigate the effects of a short acquisition time on the image quality and Aß detectability of AV45 PET. Methods: In this cross-sectional study, 29 patients with Alzheimer's disease (AD) and 13 healthy participants underwent 15-minute AV45 PET/magnetic resonance imaging scanning. The PET data were subsequently reconstructed into 15-, 10-, 8-, 6-, 4-, 2-, and 1-minute duration groups (G15, G10, G8, G6, G4, G2, and G1). Subjective PET image quality was scored based on a 5-point Likert scale (poor-excellent: 1-5), and objective image quality was evaluated by the signal-to-noise ratio (SNR) of the 1 cm3 region of interest (ROI) inside the cerebellum. Aß detectability was assessed by the calculation of regional standardized uptake value ratio (SUVR) values in all groups. The Kruskal-Wallis rank sum test and paired t-test were performed to compare the subjective scores, SNR, and SUVR values. The visual inspection was also performed by 2 nuclear physicians to give a binary diagnosis to each case. Results: The subjective scores were decreased in the groups with shortened scanning time relative to the G15 group (4.67±0.48, all P<0.05). Notably, a good image quality score was also given to the G10 group (4.40±0.63), and sufficient image quality could be achieved with the G8 (3.86±0.68) and G6 (3.14±0.52) groups. The SNR values were decreased by 10.33%, 17.74%, and 23.26% in the G10, G8, and G6 group, respectively (all P<0.05). Compared with the G15 group (1.48±0.16), the composite SUVR values were increased in the G10 (1.50±0.16), G8 (1.50±0.17), and G6 groups (1.51±0.18, all P<0.05). By visual inspection, the diagnoses of each case in the G10, G8, and G6 group were identical with those in the G15 group. Conclusions: The acquisition time of AV45 PET is required to reach at least 6 minutes to achieve acceptable image quality and maintained Aß detectability.

10.
Cell ; 186(22): 4773-4787.e12, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37806310

RESUMO

Pollen-pistil interactions establish interspecific/intergeneric pre-zygotic hybridization barriers in plants. The rejection of undesired pollen at the stigma is crucial to avoid outcrossing but can be overcome with the support of mentor pollen. The mechanisms underlying this hybridization barrier are largely unknown. Here, in Arabidopsis, we demonstrate that receptor-like kinases FERONIA/CURVY1/ANJEA/HERCULES RECEPTOR KINASE 1 and cell wall proteins LRX3/4/5 interact on papilla cell surfaces with autocrine stigmatic RALF1/22/23/33 peptide ligands (sRALFs) to establish a lock that blocks the penetration of undesired pollen tubes. Compatible pollen-derived RALF10/11/12/13/25/26/30 peptides (pRALFs) act as a key, outcompeting sRALFs and enabling pollen tube penetration. By treating Arabidopsis stigmas with synthetic pRALFs, we unlock the barrier, facilitating pollen tube penetration from distantly related Brassicaceae species and resulting in interspecific/intergeneric hybrid embryo formation. Therefore, we uncover a "lock-and-key" system governing the hybridization breadth of interspecific/intergeneric crosses in Brassicaceae. Manipulating this system holds promise for facilitating broad hybridization in crops.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Hormônios Peptídicos , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Brassicaceae/genética , Brassicaceae/metabolismo , Hormônios Peptídicos/metabolismo , Peptídeos/metabolismo , Pólen/metabolismo , Tubo Polínico/metabolismo , Isolamento Reprodutivo
11.
Front Endocrinol (Lausanne) ; 14: 1232361, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795370

RESUMO

Introduction: The addition of antagonists is mainly based on estrogen level and follicle size, while LH level has not received sufficient attention.In this study, LH Level on the antagonist administration day was used as the main research objective to explore its relationship with laboratory indicators and pregnancy outcomes. Methods and Analysis: We enrolled 854 patients with normal ovarian function undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) between May 2021 to May 2022 at the Reproductive Center of Shandong University of Traditional Chinese Medicine.We used the quartile method to group LH levels on the antagonist administration day. There were four groups: Q1 (0.53IU/L≤LH ≤ 1.89IU/L); Q2 (1.89IU/L

Assuntos
Hormônio Liberador de Gonadotropina , Indução da Ovulação , Masculino , Gravidez , Feminino , Humanos , Indução da Ovulação/métodos , Sêmen , Fertilização in vitro/métodos , Ovário
12.
Front Neurol ; 14: 1220473, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37638192

RESUMO

Objective: Idiopathic normal-pressure hydrocephalus (iNPH) is a treatable cause of dementia; however, its etiology and pathogenesis remain poorly understood. The objective of this study was to investigate the prevalence and impact of vascular risk factors in patients with iNPH compared to a control cohort to better understand the potential mechanisms and preventive measures. Methods: We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library (from inception to December 20, 2022) for studies reporting vascular risk factors for the development of iNPH. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects models. Results: After screening 1,462 articles, 11 case-control studies comprising 1,048 patients with iNPH and 79,668 cognitively unimpaired controls were included in the meta-analysis. Our data showed that hypertension (N = 991, OR = 2.30, 95% CI 1.64 to 3.23, I2= 64.0%), diabetes mellitus (DM) (N = 985, OR = 3.12, 95% CI 2.29 to 4.27, I2= 44.0%), coronary heart disease (CHD; N = 880, OR = 2.34, 95% CI 1.33 to 4.12, I2= 83.1%), and peripheral vascular disease (N = 172, OR = 2.77, 95% CI 1.50 to 5.13, I2= 0.0%) increased the risk for iNPH, while overweight was a possible factor (N = 225, OR = 2.01, 95% CI 1.34 to 3.04, I2= 0.0%) based on the sensitivity analysis. Smoking and alcohol consumption were not associated with iNPH. Conclusions: Our study suggested that hypertension, DM, CHD, peripheral vascular disease, and overweight were associated with iNPH. These factors might be involved in the pathophysiological mechanisms promoting iNPH. These findings require further investigation in future studies. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42022383004.

13.
Angew Chem Int Ed Engl ; 62(10): e202216309, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36622129

RESUMO

Propylene gas is produced worldwide by steam cracking on million-metric-ton scale per year. It serves as a valuable starting material for π-bond functionalization but is rarely applied in transition metal-catalyzed allylic C-H functionalization for fine chemical synthesis. Herein, we report that a newly-developed cationic cyclopentadienyliron dicarbonyl complex allows for the conversion of propylene to its allylic C-C bond coupling products under catalytic conditions. This approach was also found applicable to the allylic functionalization of simple α-olefins with distinctive branched selectivity. Experimental and computational mechanistic studies supported the allylic deprotonation of the metal-coordinated alkene as the turnover-limiting step and led to insights into the multifaceted roles of the newly designed ligand in promoting allylic C-H functionalization with enhanced reactivity and stereoselectivity.

14.
Talanta ; 251: 123789, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35988345

RESUMO

Herein, lysozyme-encapsulated gold nanoclusters (AuNCs@Lzm, AuL) were favorably obtained by a simple and economical synthesis. The resulting AuL exhibits low toxicity, exceptional stability and intense red fluorescence at 650 nm, which can enter living cells and is mainly located in lysosomes. The AuL selectively and sensitively drove to detect folic acid (FA) with a detection limit as low as 0.19 nM based on the combination of the static quenching and the internal filtering effect. Interestingly, the fascinating results discovered that the AuL with ignorable toxicity was adsorbed from the intestine into the liver, and essentially was cleared from the body in 6 days without significant bioaccumulation in zebrafish. Furthermore, the hyaluronic acid (HA) coating AuLH exhibits remarkably targeted tumors towards MCF-7>HeLa > HepG2¼NIH/3T3≈DC, which attributed to the number of receptors expressed by the cells. All these advantages highlight that the AuL is a versatile nanoplatform for sensing, in vivo fluorescence imaging and tumor targeting.


Assuntos
Ouro , Nanopartículas Metálicas , Animais , Ácido Fólico , Ácido Hialurônico , Muramidase , Peixe-Zebra
15.
HLA ; 100(5): 479-490, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36227705

RESUMO

Dogs have served as one of the most reliable preclinical models for a variety of diseases and treatments, including stem/progenitor cell transplantation. At the genetic epicenter of dog transplantation models, polymorphic major histocompatibility complex (MHC) genes are most impactful on transplantation success. Among the canine class I and class II genes, DLA-88 has been best studied in transplantation matching and outcomes, with 129 DLA-88 alleles identified. In this study we developed and tested a next generation (NGS) sequencing protocol for rapid identification of DLA-88 genotypes in dogs and compared the workflow and data generated with an established DLA-88 Sanger sequencing protocol that has been in common prior use for clinical studies. By testing the NGS protocol on a random population of 382 dogs, it was possible to demonstrate superior efficacy based on laboratory execution and overall cost. In addition, NGS proved far more effective at discovering new alleles and detecting multiple alleles associated with gene duplication. A total of 51 new DLA-88 alleles are reported here. This rate of new allele discovery indicates that a large pool of yet un-discovered DLA-88 alleles exists in the domestic dog population. In addition, more than 46% of dogs carried three or more copies of DLA-88, further emphasizing the need for more sensitive and cost-effective DLA typing methodology for the dog clinical model.


Assuntos
Duplicação Gênica , Antígenos de Histocompatibilidade Classe I , Alelos , Animais , Cães , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos de Histocompatibilidade Classe I/genética
16.
Environ Int ; 169: 107536, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36152365

RESUMO

The bioconcentration factor (BCF) is a key parameter for bioavailability assessment of environmental pollutants in regulatory frameworks. The comparative toxicology and mechanism of action of congeners are also of concern. However, there are limitations to acquire them by conducting field and laboratory experiments while machinelearning is emerging as a promising predictive tool to fill the gap. In this study, the Direct Message Passing Neural Network (DMPNN) was applied to predict logBCFs of bisphenol A (BPA) and its four analogues (bisphenol AF (BPAF), bisphenol B (BPB), bisphenol F (BPF) and bisphenol S (BPS)). For the test set, the Pearson correlation coefficient (PCC) and mean square error (MSE) were 0.85 and 0.52 respectively, suggesting a good predictive performance. The predicted logBCFs values by the DMPNN ranging from 0.35 (BPS) to 2.14 (BPAF) coincided well with those by the classical EPI Suite (BCFBAF model). Besides, estrogen receptor α (ERα) bioactivity of these bisphenols was also predicted well by the DMPNN, with a probability of 97.0 % (BPB) to 99.7 % (BPAF), which was validated by the extent of vitellogenin (VTG) induction in male zebrafish as a biomarker except BPS. Thus, with little need for expert knowledge, DMPNN is confirmed to be a useful tool to accurately predict logBCF and screen for estrogenic activity from molecular structures. Moreover, a gender difference was noted in the changes of three endpoints (logBCF, ER binding affinity and VTG levels), the rank order of which was BPAF > BPB > BPA > BPF > BPS consistently, and abnormal amino acid metabolism is featured as an omics signature of abnormal hormone protein expression.


Assuntos
Poluentes Ambientais , Peixe-Zebra , Aminoácidos , Animais , Compostos Benzidrílicos/análise , Bioacumulação , Poluentes Ambientais/toxicidade , Receptor alfa de Estrogênio/metabolismo , Estrona , Fluorocarbonos , Masculino , Redes Neurais de Computação , Fenóis , Receptores de Estrogênio/metabolismo , Sulfonas , Vitelogeninas/metabolismo , Peixe-Zebra/metabolismo
17.
Nucleic Acids Res ; 50(W1): W761-W767, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35554556

RESUMO

Immune checkpoint blockade (ICB) therapy has been successfully applied to clinically therapeutics in multiple cancers, but its efficacy varies greatly among different patients and cancer types. Therefore, the construction of gene signatures to identify patients who could benefit from ICB therapy is particularly important for precision cancer treatment. However, due to the lack of a user-friendly platform, the construction of such gene signatures is a great challenge for clinical investigators who have limited programming skills. In light of this challenge, we developed a web server called Tumor Immunotherapy Response Signature Finder(TIRSF) for the construction of gene signatures to predict ICB therapy response in cancer patients. TIRSF consists of three functional modules. The first module is the Signature Discovery module which provides signature construction and performance evaluation functionalities. The second is a module for response prediction based on the TIRSF signatures, which enables response prediction and prognostic analysis of immunotherapy samples. The last is a module for response prediction based on existing signatures. This module currently integrates 24 published signatures for ICB therapy response prediction. Together, all of above features can be freely accessed at http://tirsf.renlab.org/.


Assuntos
Biomarcadores Tumorais , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Prognóstico , Imunoterapia
18.
Sci Total Environ ; 809: 151103, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-34743883

RESUMO

In our previous studies, it was found that graphene oxide (GO) reduced the endocrine disruption of bisphenol A (BPA) in zebrafish embryo and larvae, but through different mechanisms. In this study, adult male zebrafish were selected to further understand the interactions between GO and BPA considering that adult zebrafish have different uptake pathways and metabolism from embryo and larvae. BPA was predicted to bind with the estrogen receptor α (ERα) with a probability of 98.1% by training a directed-message passing deep neural network model, and was confirmed by molecular docking analysis. The results were in accordance with the significantly increased vitellogenin (VTG) and estradiol (E2) levels, while decreased testosterone (T) and follicle-stimulating hormone (FSH) levels in the adult male zebrafish after 7 d exposure to 500 µg/L BPA. Compared to BPA single exposure group, the presence of GO led to significantly lower T and FSH levels and fewer spermatozoa, indicating that GO enhanced the endocrine disruption effects of BPA in the adult zebrafish. Metabolomics analysis revealed that 5 µg/L BPA could elicit changes in the metabolome, and the responses were correlated with BPA concentrations. Metabolic pathway analysis revealed more disturbance was caused by the mixture of GO and BPA compared to BPA alone, including three additional pathways and stronger perturbations on carbohydrate, lipid, and amino acid metabolism, fortifying that GO exaggerated the toxic effects of BPA. This was opposite to the depression effect observed in zebrafish embryo and larvae, magnifying that the joint effects of exposure to nanomaterials and endocrine disrupting chemicals are relevant to the life stages of organisms.


Assuntos
Aprendizado Profundo , Disruptores Endócrinos , Poluentes Químicos da Água , Animais , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Grafite , Masculino , Metabolômica , Simulação de Acoplamento Molecular , Fenóis , Peixe-Zebra
19.
J Vasc Surg ; 75(4): 1440-1449.e5, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34788653

RESUMO

OBJECTIVE: Atherosclerosis obliterans (ASO) is a chronic occlusive arterial disease and the most common type of peripheral arterial disease. Current treatment options like medication and vascularization have limited effects for "no-option" patients, and stem cell therapy is considered a viable option, although its application and efficacy have not been standardized. The objective of this review was to assess the safety and efficacy of autologous stem cell therapy in patients with ASO. METHODS: We performed a literature search of published randomized controlled trials (RCTs) for patients with ASO receiving stem cell therapy without a revascularization option. PubMed, Embase, and the Cochrane Library were searched. This study was conducted by a pair of authors independently and audited by a third author. Data were synthesized with a random-effects model. RESULTS: A total of 630 patients in 12 RCTs were included. The results showed that cell therapy significantly improved total amputation (relative risk [RR], 0.64; 95% confidence interval [CI], 0.47-0.87; P = .004), major amputation (RR, 0.69; 95% CI, 0.50-0.94; P = .02), ankle-brachial index (mean difference [MD], 0.08; 95% CI, 0.02-0.13; P = .004), transcutaneous oxygen tension (MD, 11.52; 95% CI, 3.60-19.43; P = .004), and rest pain score (MD, -0.64; 95% CI, -1.10 to -0.17; P = .007) compared with placebo or standard care. However, current studies showed cell therapy was not superior to placebo or standard care in all-cause death (RR, 0.75; 95% CI, 0.41-1.36; P = .34) and ulcer size (MD, -8.85; 95% CI, -29.05 to 11.36; P = .39). The number of trials included was limited. Moreover, most trials were designed for "no-option" patients, and thus the results should be applied with caution to other patients with peripheral arterial disease. CONCLUSIONS: Patients with ASO can benefit from autologous cell therapy in limb salvage, limb blood perfusion, and rest pain alleviation.


Assuntos
Doença Arterial Periférica , Humanos , Dor , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante de Células-Tronco/efeitos adversos , Transplante Autólogo
20.
J Am Chem Soc ; 143(37): 14998-15004, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34491051

RESUMO

An iron-catalyzed C-H functionalization of simple monosubstituted allenes is reported. An efficient protocol for this process was made possible by the use of a newly developed electron-rich and sterically hindered cationic cyclopentadienyliron dicarbonyl complex as the catalyst and N-sulfonyl hemiaminal ether reagents as precursors to iminium ion electrophiles. Under optimized conditions, the use of a mild, functional-group-tolerant base enabled the conversion of a range of monoalkyl allenes to their allenylic sulfonamido 1,1-disubstituted derivatives, a previously unreported and contrasteric regiochemical outcome for the C-H functionalization of electronically unbiased and directing-group-free allenes.


Assuntos
Alcadienos/síntese química , Hidrocarbonetos/síntese química , Ferro/química , Alcadienos/química , Catálise , Hidrocarbonetos/química , Ligação de Hidrogênio , Modelos Moleculares , Estrutura Molecular
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