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1.
Micron ; 185: 103686, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38981387

RESUMO

A new real space HAADF simulation method was described in detail and a Real Space- STEM software was developed based on the new simulation method. The algorithm of the real space method can quickly calculate and simulate the microstructure images of complex crystals. The Real Space-STEM software developed in this paper has the functions of HRTEM and HAADF image simulation based on the real space method. By using this software to simulate high-resolution images of representative crystal materials from each crystal system, the HAADF images are both accurate and efficient. The effect of STEM parameters on HAADF imaging has been discussed using simulation results.

2.
Plant J ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037746

RESUMO

The advanced model of floral morphogenesis is based largely on data from Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), but this process is less well understood in the Triticeae. Here, we investigated a sterile barley (Hordeum vulgare) mutant with malformed floral organs (designated mfo1), of which the paleae, lodicules, and stamens in each floret were all converted into lemma-like organs, and the ovary was abnormally shaped. Combining bulked-segregant analysis, whole-genome resequencing, and TILLING approaches, the mfo1 mutant was attributed to loss-of-function mutations in the MADS-box transcription factor gene HvAGL6, a key regulator in the ABCDE floral morphogenesis model. Through transcriptomic analysis between young inflorescences of wild-type and mfo1 plants, 380 genes were identified as differentially expressed, most of which function in DNA binding, protein dimerization, cell differentiation, or meristem determinacy. Regulatory pathway enrichment showed HvAGL6 associates with transcriptional abundance of many MADS-box genes, including the B-class gene HvMADS4. Mutants with deficiency in HvMADS4 exhibited the conversion of stamens into supernumerary pistils, producing multiple ovaries resembling the completely sterile multiple ovaries 3.h (mov3.h) mutant. These findings demonstrate that the regulatory model of floral morphogenesis is conserved across plant species and provides insights into the interactions between HvAGL6 and other MADS-box regulators.

3.
J Hazard Mater ; 476: 134960, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901250

RESUMO

Human exposure to micro- and nano-plastics (MNPs) primarily occurs through respiration and diet in the environment. However, the early effects and warning signs of MNPs exposure on vertebrates are unclear. Here we used intratracheal instillation and intragastric infusion to establish mouse models for MNPs exposure to systematically investigate the toxic mechanisms of MNPs on endocrine organs. Results showed that MNPs induced endocrine disruptions in short-term exposure by both dietary and respiratory pathways. Microplastics (MPs) exposed through dietary route were more toxic to thyroid gland, whereas nanoplastics (NPs) exhibited the highest level of toxicity to parathyroid gland through respiration. The transcriptome and validation of related functional genes revealed that MNPs affected the synthesis of thyroglobulin by interfering with the expressions of PAX8 and CREB. MNPs also impacted the levels of thyroid stimulating hormone, further mediating the secretion of thyroid hormones. Moreover, MNPs modulate the expression of Mafb, thereby exerting regulatory effects on parathyroid hormone (PTH) synthesis and growth development in parathyroid cells. Meanwhile, MNPs interfered with the expression of IP3R in the calcium signaling pathway, indirectly affecting the secretion of PTH. This study reveals the effects and mechanisms of MNPs on thyroid and parathyroid and highlights the significance of early warning of MNPs exposure.

4.
Front Microbiol ; 15: 1411251, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903784

RESUMO

The large amount of various types of heavy metals in animal manure applied to agricultural field has caused severe threat to the ecosystems of soil environments. In this study, the effect of thermal treatment of illite on the bioavailability of copper (Cu) and zinc (Zn) in the aerobic composting of pig manure with corn straw biochar was investigated. The objectives of this study were to characterize the variations in the bioavailability of Cu and Zn in the aerobic composting of pig manure added with illite treated with high temperatures and to identify the relatively dominant microbes involved in the formation of humus and passivation of heavy metals in pig manure composting based on 16S rRNA high-throughput sequencing analysis. The results showed that in comparison with the raw materials of pig manure, the bioavailability of Zn and Cu in the control and three experimental composting groups, i.e., group I (with untreated illite), group I-2 (with illite treated under 200°C), and group I-5 (with illite treated under 500°C), was decreased by 27.66 and 71.54%, 47.05 and 79.80%, 51.56 and 81.93%, and 58.15 and 86.60%, respectively. The results of 16S rRNA sequencing analysis revealed that in the I-5 group, the highest relative abundance was detected in Fermentimonas, which was associated with the degradation of glucose and fructose, and the increased relative abundances were revealed in the microbes associated with the formation of humus, which chelated with Zn and Cu to ultimately reduce the bioavailability of heavy metals and their biotoxicity in the compost. This study provided strong experimental evidence to support the application of illite in pig manure composting and novel insights into the selection of appropriate additives (i.e., illite) to promote humification and passivation of different heavy metals in pig manure composting.

5.
Theor Appl Genet ; 137(7): 165, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904787

RESUMO

KEY MESSAGE: A grain weight locus from Agropyron cristatum chromosome 5P increases grain weight in different wheat backgrounds and is localized to 5PL (bin 7-12). Thousand-grain weight is an important trait in wheat breeding, with a narrow genetic basis being the main factor limiting improvement. Agropyron cristatum, a wild relative of wheat, harbors many desirable genes for wheat improvement. Here, we found that the introduction of the 5P chromosome from A. cristatum into wheat significantly increased the thousand-grain weight by 2.55-7.10 g, and grain length was the main contributor to grain weight. An increase in grain weight was demonstrated in two commercial wheat varieties, indicating that the grain weight locus was not affected by the wheat background. To identify the chromosome segment harboring the grain weight locus, three A. cristatum 5P deletion lines, two wheat-A. cristatum 5P translocation lines and genetic populations of these lines were used to evaluate agronomic traits. We found that the translocation lines harboring the long arm of A. cristatum chromosome 5P (5PL) exhibited high grain weight and grain length, and the genetic locus associated with increased grain weight was mapped to 5PL (bin 7-12). An increase in grain weight did not adversely affect other agronomic traits in translocation line 5PT2, which is a valuable germplasm resource. Overall, we identified a grain weight locus from chromosome 5PL and provided valuable germplasm for improving wheat grain weight.


Assuntos
Agropyron , Mapeamento Cromossômico , Cromossomos de Plantas , Grão Comestível , Fenótipo , Melhoramento Vegetal , Locos de Características Quantitativas , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Agropyron/genética , Agropyron/crescimento & desenvolvimento , Cromossomos de Plantas/genética , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Sementes/genética , Introgressão Genética , Translocação Genética
6.
J Am Chem Soc ; 146(23): 16173-16183, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38819260

RESUMO

Genetically encoding a proximal reactive warhead into the protein binder/drug has emerged as an efficient strategy for covalently binding to protein targets, enabling broad applications. To expand the reactivity scope for targeting the diverse natural residues under physiological conditions, the development of a genetically encoded reactive warhead with excellent stability and broad reactivity is highly desired. Herein, we reported the genetic encoding of epoxide-containing tyrosine (EPOY) for developing covalent protein drugs. Our study demonstrates that EPOY, when incorporated into a nanobody (KN035), can cross-link with different side chains (mutations) at the same position of PD-L1 protein. Significantly, a single genetically encoded reactive warhead that is capable of covalent and site-specific targeting to 10 different nucleophilic residues was achieved for the first time. This would largely expand the scope of covalent warhead and inspire the development of covalent warheads for both small-molecule drugs and protein drugs. Furthermore, we incorporate the EPOY into a designed ankyrin repeat protein (DarpinK13) to create the covalent binders of KRAS. This covalent KRAS binder holds the potential to achieve pan-covalent targeting of KRAS based on the structural similarity among all oncogenic KRAS mutants while avoiding off-target binding to NRAS/HRAS through a covalent interaction with KRAS-specific residues (H95 and E107). We envision that covalently targeting to H95 will be a promising strategy for the development of covalent pan-KRAS inhibitors in the future.


Assuntos
Compostos de Epóxi , Humanos , Compostos de Epóxi/química , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/química , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Tirosina/química , Antígeno B7-H1/química , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/metabolismo
7.
Sci Adv ; 10(15): eadn3924, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38598633

RESUMO

Our extensive field studies demonstrate that saline groundwater inland and freshened groundwater offshore coexist in the same aquifer system in the Pearl River delta and its adjacent shelf. This counterintuitive phenomenon challenges the commonly held assumption that onshore groundwater is typically fresh, while offshore groundwater is saline. To address this knowledge gap, we conduct a series of sophisticated paleo-hydrogeological models to explore the formation mechanism and evolution process of the groundwater system in the inland-shelf systems. Our findings indicate that shelf freshened groundwater has formed during the lowstands since late Pleistocene, while onshore saline groundwater is generated by paleo-seawater intrusion during the Holocene transgression. This reveals that terrestrial and offshore groundwater systems have undergone alternating changes on a geological timescale. The groundwater system exhibits hysteresis responding to paleoclimate changes, with a lag of 7 to 8 thousand years, suggesting that paleoclimatic forcings exert a significantly residual influence on the present-day groundwater system.

8.
Theor Appl Genet ; 137(5): 110, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656338

RESUMO

KEY MESSAGE: We developed T1AL·1PS and T1AS·1PL Robertsonian translocations by breakage-fusion mechanism based on wheat-A. cristatum 1P(1A) substitution line with smaller leaf area, shorter plant height, and other excellent agronomic traits Agropyron cristatum, a wild relative of wheat, is a valuable germplasm resource for improving wheat genetic diversity and yield. Our previous study confirmed that the A. cristatum chromosome 1P carries alien genes that reduce plant height and leaf size in wheat. Here, we developed T1AL·1PS and T1AS·1PL Robertsonian translocations (RobTs) by breakage-fusion mechanism based on wheat-A. cristatum 1P (1A) substitution line II-3-1c. Combining molecular markers and cytological analysis, we identified 16 spontaneous RobTs from 911 F2 individuals derived from the cross of Jimai22 and II-3-1c. Fluorescence in situ hybridization (FISH) was applied to detect the fusion structures of the centromeres in wheat and A. cristatum chromosomes. Resequencing results indicated that the chromosomal junction point was located at the physical position of Triticum aestivum chromosome 1A (212.5 Mb) and A. cristatum chromosome 1P (230 Mb). Genomic in situ hybridization (GISH) in pollen mother cells showed that the produced translocation lines could form stable ring bivalent. Introducing chromosome 1PS translocation fragment into wheat significantly increased the number of fertile tillers, grain number per spike, and grain weight and reduced the flag leaf area. However, introducing chromosome 1PL translocation fragment into wheat significantly reduced flag leaf area and plant height with a negative effect on yield components. The pre-breeding of two spontaneous RobTs T1AL·1PS and T1AS·1PL was important for wheat architecture improvement.


Assuntos
Agropyron , Cromossomos de Plantas , Melhoramento Vegetal , Translocação Genética , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Triticum/anatomia & histologia , Agropyron/genética , Agropyron/crescimento & desenvolvimento , Cromossomos de Plantas/genética , Hibridização in Situ Fluorescente , Fenótipo
9.
Int J Neurosci ; : 1-11, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38682651

RESUMO

OBJECTIVE: Acute Stanford Type A aortic dissection (AAAD) is a critical condition in vascular surgery, and total aortic arch replacement surgery is the preferred method to save patients' lives. In recent years, as clinical research has advanced, there has been a growing realization of the close association between poor postoperative outcomes in patients and neurological functional deficits. Neurological function monitoring is a medical technique used to evaluate and monitor the functional status of the nervous system. METHODS: This monitoring involves the assessment of various aspects of the nervous system, including but not limited to nerve conduction velocity, neuromuscular function, electroencephalographic activity, and sensory nerve transmission. Neurological function monitoring has broad clinical applications and can be used to diagnose and monitor many neurological disorders, helping physicians understand patients' neurological functional status and guide treatment plans. During the postoperative recovery process, neurological function monitoring can assist physicians in assessing the potential impact of surgery on the nervous system and monitor the recovery of patients' neurological function. RESULTS: Studies have shown that neurological function monitoring holds promise in predicting neurological functional prognosis and interventions for patients with aortic dissection. CONCLUSION: Therefore, the primary objective of this study is to evaluate the effectiveness and reliability of various intraoperative neurological monitoring techniques, neuroimaging examinations, and biomarkers in predicting and assessing postoperative neurological outcomes in patients undergoing AAAD surgery.

10.
Front Pharmacol ; 15: 1342121, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529184

RESUMO

Objective: Our previous studies substantiated that the biological activity of Schisandra chinensis lignans during the treatment of Alzheimer's disease (AD) was mediated by neurotransmitter levels, and 15 of its active components were identified. However, the pharmacokinetic and pharmacodynamic relationship of Schisandra chinensis lignans has been less studied. The objective of this study was to investigate the relationship between the pharmacokinetics and pharmacodynamics of Schisandra chinensis lignans in the treatment of AD, and to establish a pharmacokinetic-pharmacodynamic (PK-PD) model. Methods and Results: Herein, we established a microdialysis-ultra performance liquid chromatography-triple quadruple mass spectrometry (MD-LC-TQ-MS) technique that could simultaneously and continuously collect and quantitatively analyze the active compounds and neurotransmitters related to the therapeutic effects of Schisandra chinensis in awake AD rats. Eight lignans were detected in the hippocampus, and a PK-PD model was established. The fitted curves highlighted a temporal lag between the maximum drug concentration and the peak drug effect. Following treatment, the levels of four neurotransmitters tended to converge with those observed in the sham operation group. Conclusion: By establishing a comprehensive concentration-time-effect relationship for Schisandra chinensis lignans in AD treatment, our study provides novel insights into the in vivo effects of these lignans in AD rats.

11.
Poult Sci ; 103(5): 103611, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38471226

RESUMO

The aim of this study was to develop an efficient and accurate platform for the detection of the newly identified goose megrivirus (GoMV). To achieve this goal, we developed a TaqMan real-time PCR technology for the rapid detection and identification of GoMV. Our data showed that the established TaqMan real-time PCR assay had high sensitivity, with the lowest detection limit of 67.3 copies/µL. No positive signal can be observed from other goose origin viruses (including AIV, GPV, GoCV, GHPyV, and GoAstV), with strong specificity. The coefficients of variation of repeated intragroup and intergroup tests were all less than 1.5%, with excellent repeatability. Clinical sample investigation data from domestic Minbei White geese firstly provided evidence that GoMV can be transmitted both horizontally and vertically. In conclusion, since the TaqMan real-time PCR method has high sensitivity, specificity, and reproducibility, it can be a useful candidate tool for GoMV epidemiological investigation.


Assuntos
Gansos , Doenças das Aves Domésticas , Reação em Cadeia da Polimerase em Tempo Real , Animais , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Reação em Cadeia da Polimerase em Tempo Real/métodos , Gansos/virologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/diagnóstico , Sensibilidade e Especificidade , Infecções por Vírus de RNA/veterinária , Infecções por Vírus de RNA/virologia , Infecções por Vírus de RNA/diagnóstico , Reprodutibilidade dos Testes
12.
Theor Appl Genet ; 137(4): 82, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489037

RESUMO

KEY MESSAGE: A novel locus on Agropyron cristatum chromosome 6P that increases grain number and spikelet number was identified in wheat-A. cristatum derivatives and across 3 years. Agropyron cristatum (2n = 4x = 28, PPPP), which has the characteristics of high yield with multiple flowers and spikelets, is a promising gene donor for wheat high-yield improvement. Identifying the genetic loci and genes that regulate yield could elucidate the genetic variations in yield-related traits and provide novel gene sources and insights for high-yield wheat breeding. In this study, cytological analysis and molecular marker analysis revealed that del10a and del31a were wheat-A. cristatum chromosome 6P deletion lines. Notably, del10a carried a segment of the full 6PS and 6PL bin (1-13), while del31a carried a segment of the full 6PS and 6PL bin (1-8). The agronomic characterization and genetic population analysis confirmed that the 6PL bin (9-13) brought about an increase in grain number per spike (average increase of 10.43 grains) and spikelet number per spike (average increase of 3.67) over the three growing seasons. Furthermore, through resequencing, a multiple grain number locus was mapped to the physical interval of 593.03-713.89 Mb on chromosome 6P of A. cristatum Z559. The RNA-seq analysis revealed the expression of 537 genes in the del10a young spike tissue, with the annotation indicating that 16 of these genes were associated with grain number and spikelet number. Finally, a total of ten A. cristatum-specific molecular markers were developed for this interval. In summary, this study presents novel genetic material that is useful for high-yield wheat breeding initiatives to meet the challenge of global food security through enhanced agricultural production.


Assuntos
Agropyron , Agropyron/genética , Melhoramento Vegetal , Cromossomos de Plantas/genética , Triticum/genética , Grão Comestível/genética , Loci Gênicos
13.
J Org Chem ; 89(5): 3441-3452, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38377488

RESUMO

We reported an efficient three-component reaction to access new spiro heterocycles through the annulation reactions of isatins, substituted ureas, and cyclic ketones under normal laboratory conditions, which is another example of isatins being used to build spiro compounds by the ring-opening and recyclization processes. The wide range of substrates, simple operation, normal experimental conditions, and high yields make the approach of high practical value.

14.
Vet Res ; 55(1): 26, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414065

RESUMO

Pyroptosis is a form of programmed cell death characterized by cell swelling, pore formation in the plasma membrane, lysis, and releases of cytoplasmic contents. To date, the molecular mechanism of human and murine Gasdermin D-mediated pyroptosis have been fully investigated. However, studies focusing on molecular mechanism of bovine Gasdermin D (bGSDMD)-mediated pyroptosis and its function against pathogenic infection were unclear. In the present study, we demonstrate that bovine caspase-1 (bCaspase-1) cleaves bGSDMD at amino acid residue D277 to produce an N-terminal fragment (bGSDMD-p30) which leads to pyroptosis. The amino acid residues T238 and F239 are critical for bGSDMD-p30-mediated pyroptosis. The loop aa 278-299, L293 and A380 are the key sites for autoinhibitory structure of the full length of bGSDMD. In addition, bCaspase-3 also cleaves bGSDMD at residue Asp86 without inducing cell death. Therefore, our study provides the first detailed elucidation of the mechanism of bovine GSDMD-mediated pyroptosis. The results will establish a significant foundation for future research on the role of pyroptosis in bovine infectious diseases.


Assuntos
Gasderminas , Piroptose , Animais , Bovinos , Humanos , Camundongos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Aminoácidos , Inflamassomos/metabolismo
15.
Am J Transl Res ; 16(1): 155-162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322568

RESUMO

OBJECTIVES: To investigate the effects of music combined with dexmedetomidine on perioperative anxiety and postoperative recovery in gynecologic laparoscopic patients. METHODS: A total of 82 female patients were enrolled in this study. Patients were randomized to the patient-preferred Music+Dexmedetomidine group (M+DEX group, n=41) and the Dexmedetomidine group (DEX group, n=41). Prior to the induction of anesthesia, dexmedetomidine was pumped intravenously at 0.5 µg/kg for 10 minutes in both groups and then maintained at 0.2 µg/kg/hour until 30 minutes before the end of surgery. In contrast to the patients in the DEX group, the patients in the M+DEX group listened to 5 minutes of their favorite music during dexmedetomidine infusion. The primary outcome was the patient's preoperative State Anxiety Inventory (SAI) score. The secondary outcomes included visual analog scale (VAS) pain scores and QoR-15 scores at 24 hours postoperatively. RESULTS: The clinical data of a total of 82 patients were analyzed. After the music intervention, we found that the preoperative SAI scores were lower in the M+DEX group than in the DEX group (37.9±5.6 vs. 41.5±6.9; P=0.01). The M+DEX group had lower VAS scores at 24 hours postoperatively than the DEX group (1 (1.0, 2.0) vs. 2 (2.0, 3.0), P < 0.01), and the M+DEX group had higher QoR-15 scores at 24 hours after the surgery than the DEX group (127.7±10.0 vs. 122.3±11.2; P=0.03). CONCLUSION: Patients undergoing gynecologic laparoscopic surgery who listened to their favorite music before the induction of anesthesia had less preoperative anxiety and recovered better 24 hours postoperatively than those who only received dexmedetomidine.

16.
Reprod Toxicol ; 124: 108552, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38296003

RESUMO

A widely used type II pyrethroid pesticide cypermethrin (CYP) is one of endocrine disrupting chemicals (EDCs) with anti-androgenic activity to induce male reproductive toxicology. However, the mechanisms have not been fully elucidated. This study was to explore the effects of CYP on apoptosis of mouse Sertoli cells (TM4) and the roles of endoplasmic reticulum (ER)-mitochondria coupling involving 1,4,5-trisphosphate receptor type1-glucose-regulated protein 75-voltage-dependent anion channel 1 (IP3R1-GRP75-VDAC1). TM4 were cultured with different concentrations of CYP. Flow cytometry, calcium (Ca2+) fluorescent probe, transmission electron microscopy and confocal microscopy, and western blot were to examine apoptosis of TM4, mitochondrial Ca2+, ER-mitochondria coupling, and expressions of related proteins. CYP was found to increase apoptotic rates of TM4 significantly. CYP was shown to significantly increase expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP). Concentration of mitochondrial Ca2+ was increased by CYP treatment significantly. CYP significantly enhanced ER-mitochondria coupling. CYP was shown to increase expressions of IP3R, Grp75 and VDAC1 significantly. We suggest that CYP induces apoptosis in TM4 cells by facilitating mitochondrial Ca2+ overload regulated by ER-mitochondria coupling involving IP3R1-GRP75-VDAC1. This study identifies a novel mechanism of CYP-induced apoptosis in Sertoli cells.


Assuntos
Proteínas de Choque Térmico HSP70 , Proteínas de Membrana , Piretrinas , Células de Sertoli , Camundongos , Animais , Masculino , Células de Sertoli/metabolismo , Mitocôndrias , Retículo Endoplasmático/metabolismo , Piretrinas/toxicidade , Apoptose , Cálcio/metabolismo
17.
Sci Rep ; 14(1): 1346, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228753

RESUMO

Information regarding regional arterial stiffness assessment in osteoarthritis (OA) was scarce and sometimes contradictory. We aimed to investigate the aortic, lower limb peripheral arterial stiffness and their associations with knee OA. Patients with primary knee OA and matched non-OA controls were prospectively enrolled from two medical centers in China. The carotid-femoral pulse wave velocity (cfPWV) and femoral-ankle pulse wave velocity (faPWV) were measured using a novel ultrasound technique. A total of 238 participants (including 128 patients with knee OA and 110 controls) were included. In OA patients, cfPWV was significantly higher than that of non-OA controls (9.40 ± 1.92 vs 8.25 ± 1.26 m/s, P < 0.0001). However, faPWV measurements in OA patients (12.10 ± 2.09 m/s) showed no significant difference compared with that of the controls (11.67 ± 2.52 m/s, P = 0.130). Multiple regression analysis revealed that cfPWV was independently associated with knee OA (P < 0.0001) after adjusting for the confounding factors including age, gender, smoking, mean blood pressure, body mass index, heart rate, high-sensitivity C-reactive protein and lipids profiles. In contrast, faPWV did not show independent association with knee OA (P = 0.372) when after adjusting for confounding factors. In addition, Spearman's correlation analysis showed cfPWV had a significant correlation with Kellgren-Lawrence score (rs = 0.2333, P = 0.008), but no correlation was founded between faPWV with Kellgren-Lawrence score (rs = 0.1624, P = 0.067) in OA patients. This study demonstrated that stiffening of aorta, but not lower limb arteries, was independently associated with knee OA. Our findings may call for further implementation of routine aortic stiffness assessments so as to evaluate cardiovascular risk in patients with OA.


Assuntos
Osteoartrite do Joelho , Rigidez Vascular , Humanos , Rigidez Vascular/fisiologia , Osteoartrite do Joelho/diagnóstico por imagem , Análise de Onda de Pulso/métodos , Aorta/diagnóstico por imagem , Artérias , Pressão Sanguínea/fisiologia , Fatores de Risco
18.
Soft Matter ; 20(4): 804-812, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38168697

RESUMO

Innovation in surfactant structures is an effective way to prepare new soft materials with novel applications. In this study, we synthesized a double-tailed surfactant containing two quaternary ammonium head groups (Di-C12-N2). The Di-C12-N2 solution behavior was investigated by surface tension, fluorescence, rheology, and cryo-TEM methods. Although Di-C12-N2 contained a large double-tailed hydrophobic group, the solubility of Di-C12-N2 was ∼90 mmol L-1 at 25 °C with a Krafft temperature of ∼1 °C. The increase in Di-C12-N2 concentration in the solutions led to the formation of various aggregates, including spherical micelles, worm-like micelles, multi-layered vesicles, and a rare type of small toroidal micelles. The two quaternary ammonium head groups in Di-C12-N2 led to strong electrostatic interactions between molecules, which was critical for the formation of toroidal micelles. Moreover, with an added NaCl concentration of 40 mmol L-1, the viscosity of the 5 mmol L-1Di-C12-N2 solution increased by ∼1000 times compared to the pure 5 mmol L-1Di-C12-N2 solution, revealing the high sensitivity of the unique head groups to ionic strength. This study enriches the research on the self-assembly principles of surfactants and brings new potential applications for new soft materials.

19.
J Comput Biol ; 31(2): 99-116, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38271572

RESUMO

Identifying cancer subtype-specific driver genes from a large number of irrelevant passengers is crucial for targeted therapy in cancer treatment. Recently, the rapid accumulation of large-scale cancer genomics data from multiple institutions has presented remarkable opportunities for identification of cancer subtype-specific driver genes. However, the insufficient subtype samples, privacy issues, and heterogenous of aberration events pose great challenges in precisely identifying cancer subtype-specific driver genes. To address this, we introduce privatedriver, the first model for identifying subtype-specific driver genes that integrates genomics data from multiple institutions in a data privacy-preserving collaboration manner. The process of identifying subtype-specific cancer driver genes using privatedriver involves the following two steps: genomics data integration and collaborative training. In the integration process, the aberration events from multiple genomics data sources are combined for each institution using the forward and backward propagation method of NetICS. In the collaborative training process, each institution utilizes the federated learning framework to upload encrypted model parameters instead of raw data of all institutions to train a global model by using the non-negative matrix factorization algorithm. We applied privatedriver on head and neck squamous cell and colon cancer from The Cancer Genome Atlas website and evaluated it with two benchmarks using macro-Fscore. The comparison analysis demonstrates that privatedriver achieves comparable results to centralized learning models and outperforms most other nonprivacy preserving models, all while ensuring the confidentiality of patient information. We also demonstrate that, for varying predicted driver gene distributions in subtype, our model fully considers the heterogeneity of subtype and identifies subtype-specific driver genes corresponding to the given prognosis and therapeutic effect. The success of privatedriver reveals the feasibility and effectiveness of identifying cancer subtype-specific driver genes in a data protection manner, providing new insights for future privacy-preserving driver gene identification studies.


Assuntos
Neoplasias do Colo , Privacidade , Humanos , Oncogenes , Algoritmos , Benchmarking
20.
Int J Surg ; 110(1): 119-129, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37800568

RESUMO

OBJECTIVE: This study aimed to construct and validate a clinical prediction model for surgical site infection (SSI) risk 30 days after gastrointestinal surgery. MATERIALS AND METHODS: This multicentre study involving 57 units conducted a 30-day postoperative follow-up of 17 353 patients who underwent gastrointestinal surgery at the unit from 1 March 2021 to 28 February 2022. The authors collected a series of hospitalisation data, including demographic data, preoperative preparation, intraoperative procedures and postoperative care. The main outcome variable was SSI, defined according to the Centres for Disease Control and Prevention guidelines. This study used the least absolute shrinkage and selection operator (LASSO) algorithm to screen predictive variables and construct a prediction model. The receiver operating characteristic curve, calibration and clinical decision curves were used to evaluate the prediction performance of the prediction model. RESULTS: Overall, 17 353 patients were included in this study, and the incidence of SSI was 1.6%. The univariate analysis combined with LASSO analysis showed that 20 variables, namely, chronic liver disease, chronic kidney disease, steroid use, smoking history, C-reactive protein, blood urea nitrogen, creatinine, albumin, blood glucose, bowel preparation, surgical antibiotic prophylaxis, appendix surgery, colon surgery, approach, incision type, colostomy/ileostomy at the start of the surgery, colostomy/ileostomy at the end of the surgery, length of incision, surgical duration and blood loss were identified as predictors of SSI occurrence ( P <0.05). The area under the curve values of the model in the train and test groups were 0.7778 and 0.7868, respectively. The calibration curve and Hosmer-Lemeshow test results demonstrated that the model-predicted and actual risks were in good agreement, and the model forecast accuracy was high. CONCLUSIONS: The risk assessment system constructed in this study has good differentiation, calibration and clinical benefits and can be used as a reference tool for predicting SSI risk in patients.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Fatores de Risco , Modelos Estatísticos , Estudos Prospectivos , Prognóstico , Estudos Retrospectivos
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