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1.
Int J Biol Macromol ; 272(Pt 2): 132772, 2024 May 29.
Article En | MEDLINE | ID: mdl-38821299

Bacteria and virus infections have posed a great threat to public health and personnel safety. For realizing rapid sterilization of the bacteria and virus, electrical stimulation sterilization was adopted to endow cellulose fibers with instantaneous antibacterial and antiviral properties. In the proposed strategy, the fiber is fluffed by mechanical refining, and then by means of the hydrogen bond between hydroxyl and aniline, the polyaniline (PANI) directionally grows vertically along the fine fibers via in-situ oxidative polymerization. Benefiting from the conductive polyaniline nanorod arrays on the fiber stem, the paper made from PANI modified refined fibers (PANI/BCF/P) exhibited excellent antibacterial and antiviral activity, the inhibition rates against S. aureus, E. coli, and bacteriophage MS2 can up to 100 %, 100 %, and 99.89 %, respectively when a weak voltage (2.5 V) was applied within 20 min. This study provides a feasible path for plant fiber to achieve efficient antibacterial and antiviral activity with electrical stimulation, which is of great significance for the preparation of electroactive antibacterial and antiviral green health products.

2.
Nat Commun ; 15(1): 3287, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38627412

Although asymmetric molecular design has been widely demonstrated effective for organic photovoltaics (OPVs), the correlation between asymmetric molecular geometry and their optoelectronic properties is still unclear. To access this issue, we have designed and synthesized several symmetric-asymmetric non-fullerene acceptors (NFAs) pairs with identical physical and optoelectronic properties. Interestingly, we found that the asymmetric NFAs universally exhibited increased open-circuit voltage compared to their symmetric counterparts, due to the reduced non-radiative charge recombination. From our molecular-dynamic simulations, the asymmetric NFA naturally exhibits more diverse molecular interaction patterns at the donor (D):acceptor (A) interface as compared to the symmetric ones, as well as higher D:A interfacial charge-transfer state energy. Moreover, it is observed that the asymmetric structure can effectively suppress triplet state formation. These advantages enable a best efficiency of 18.80%, which is one of the champion results among binary OPVs. Therefore, this work unambiguously demonstrates the unique advantage of asymmetric molecular geometry, unveils the underlying mechanism, and highlights the manipulation of D:A interface as an important consideration for future molecular design.

3.
Chem Sci ; 15(10): 3502-3515, 2024 Mar 06.
Article En | MEDLINE | ID: mdl-38455030

Human serum albumin (HSA), the most abundant protein in plasma and cerebrospinal fluid, not only serves as a crucial carrier of various exogenous and endogenous ligands but also modulates the aggregation of amyloidogenic proteins, including alpha synuclein (αSyn), which is associated with Parkinson's disease and other α-synucleinopathies. HSA decreases αSyn toxicity through the direct binding to monomeric and oligomeric αSyn species. However, it is possible that HSA also sequesters metal ions that otherwise promote aggregation. Cu(ii) ions, for example, enhance αSyn fibrillization in vitro, while also leading to neurotoxicity by generating reactive oxygen species (ROS). However, it is currently unclear if and how HSA affects Cu(ii)-binding to αSyn. Using an integrated set of NMR experiments, we show that HSA is able to chelate Cu(ii) ions from αSyn more efficiently than standard chelators such as EDTA, revealing an unexpected cooperativity between the HSA metal-binding sites. Notably, fatty acid binding to HSA perturbs this cooperativity, thus interfering with the sequestration of Cu(ii) ions from αSyn. We also observed that glycation of HSA diminished Cu(ii)-binding affinity, while largely preserving the degree of cooperativity between the HSA metal-binding sites. Additionally, our results show that Cu(ii)-binding to HSA stabilizes the interactions of HSA with αSyn primarily at two different regions, i.e. the N-terminus, Tyr 39 and the majority of the C-terminus. Our study not only unveils the effect of fatty acid binding and age-related posttranslational modifications, such as glycation, on the neuroprotective mechanisms of HSA, but also highlights the potential of αSyn as a viable NMR-based sensor to investigate HSA-metal interactions.

4.
Materials (Basel) ; 16(24)2023 Dec 12.
Article En | MEDLINE | ID: mdl-38138760

A hot-working die steel thick-walled tube Pilger rolling test was carried out using an LG40 Pilger mill, and the morphology and roughness evolution of the inner surface were examined using a white-light interferometer. The experimental results showed that micro-wrinkles formed on the basis of the original inner surface morphology, the altitude difference (Sz) between the peaks and valleys of the inner surface profile increased from 3.18 to 3.686 µm, and Sa increased from 0.722 to 0.892 µm in the diameter reduction zone. As the tube continued to feed into the wall thickness reduction zone, the micro-wrinkles gradually flattened, Sz and Sa were decreased to 1.625 and 0.174 respectively, and Sa maintained a slight fluctuation of 0.174~0.2 µm in the final sizing zone. From the diameters of the roller groove and taper of the mandrel, the three-dimensional strain of the tube in the wall thickness reduction zone was calculated, and the strain state of the tube in the complete deformation zone could be analyzed by finite element simulations. We found that in the diameter reduction zone, the inner surface was not supported by the mandrel and was free, while micro-wrinkles formed under circumferential compressive strain. In the wall thickness reduction zone, the deformation of the inner surface was controlled by the mandrel, and the micro-wrinkles were gradually flattened by radial compressive strain. The ratio of radial to circumferential strain was the key to flattening the micro-wrinkles, and when the ratio increased, the inner surface roughness (Sa) was reduced to 0.174 µm. In the sizing zone, the radial and circumferential strains were small, and the inner surface roughness showed no obvious fluctuation.

5.
JACS Au ; 3(12): 3485-3493, 2023 Dec 25.
Article En | MEDLINE | ID: mdl-38155658

Alpha synuclein (αS) aggregates are the main component of Lewy bodies (LBs) associated with Parkinson's disease (PD). A longstanding question about αS and PD pertains to the autosomal dominant E46K αS mutant, which leads to the early onset of PD and LB dementias. The E46K mutation not only promotes αS aggregation but also stabilizes αS monomers in "closed" conformers, which are compact and aggregation-incompetent. Hence, the mechanism of action of the E46K mutation is currently unclear. Here, we show that αS monomers harboring the E46K mutation exhibit more extensive interactions with fibrils compared to those of WT. Such monomer-fibril interactions are sufficient to allosterically drive transitions of αS monomers from closed to open conformations, enabling αS aggregation. We also show that E46K promotes head-to-tail monomer-monomer interactions in early self-association events. This multipronged mechanism provides a new framework to explain how the E46K mutation and possibly other αS variants trigger early-onset PD.

6.
Front Neurosci ; 17: 1270785, 2023.
Article En | MEDLINE | ID: mdl-38027473

Introduction: The electroencephalographic (EEG) based on the motor imagery task is derived from the physiological electrical signal caused by the autonomous activity of the brain. Its weak potential difference changes make it easy to be overwhelmed by noise, and the EEG acquisition method has a natural limitation of low spatial resolution. These have brought significant obstacles to high-precision recognition, especially the recognition of the motion intention of the same upper limb. Methods: This research proposes a method that combines signal traceability and Riemannian geometric features to identify six motor intentions of the same upper limb, including grasping/holding of the palm, flexion/extension of the elbow, and abduction/adduction of the shoulder. First, the EEG data of electrodes irrelevant to the task were screened out by low-resolution brain electromagnetic tomography. Subsequently, tangential spatial features are extracted by the Riemannian geometry framework in the covariance matrix estimated from the reconstructed EEG signals. The learned Riemannian geometric features are used for pattern recognition by a support vector machine with a linear kernel function. Results: The average accuracy of the six classifications on the data set of 15 participants is 22.47%, the accuracy is 19.34% without signal traceability, the accuracy is 18.07% when the features are the filter bank common spatial pattern (FBCSP), and the accuracy is 16.7% without signal traceability and characterized by FBCSP. Discussion: The results show that the proposed method can significantly improve the accuracy of intent recognition. In addressing the issue of temporal variability in EEG data for active Brain-Machine Interfaces, our method achieved an average standard deviation of 2.98 through model transfer on different days' data.

7.
Cell Mol Biol Lett ; 28(1): 89, 2023 Oct 27.
Article En | MEDLINE | ID: mdl-37891494

BACKGROUND: The unique expression pattern endows oncofetal genes with great value in cancer diagnosis and treatment. However, only a few oncofetal genes are available for clinical use and the underlying mechanisms that drives the fetal-like reprogramming of cancer cells remain largely unknown. METHODS: Microarray assays and bioinformatic analyses were employed to screen for potential oncofetal long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). The expression levels of MIR4435-2HG, NOP58 ribonucleoprotein (NOP58), insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) and stem markers were detected by quantitative polymerase chain reaction. The 2'-O-methylation (2'-O-Me) status of rRNA were detected through reverse transcription at low dNTP concentrations followed by PCR. The regulation of MIR4435-2HG by IGF2BP1 was explored by RNA immunoprecipitation (RIP), methylated RIP (MeRIP) and dual-luciferase assays. The interaction between MIR4435-2HG and NOP58 was investigated by RNA Pulldown, RIP and protein stability assays. In vitro and in vivo function assays were performed to detect the roles of MIR4435-2HG/NOP58 in HCC. RESULTS: MIR4435-2HG was an oncofetal lncRNA associated with poor prognosis in HCC. Functional experiments showed that overexpression of MIR4435-2HG remarkably enhanced the stem-cell properties of HCC cells, promoting tumorigenesis in vitro and in vivo. Mechanically, MIR4435-2HG directly bound NOP58 and IGF2BP1. IGF2BP1 upregulated MIR4435-2HG expression in HCC through N6-methyladenosine (m6A) modification. Moreover, MIR4435-2HG protected NOP58 from degradation, which raised rRNA 2'-O-Me levels and promoted internal ribosome entry site (IRES)-dependent translation of oncogenes. CONCLUSIONS: This study identified an oncofetal lncRNA MIR4435-2HG, characterized the role of MIR4435-2HG/NOP58 in stemness maintenance and proliferation of HCC cells, and confirmed m6A as a 'driver' that reactivated MR4435-2HG expression in HCC.


Carcinoma, Hepatocellular , Liver Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , RNA, Long Noncoding/genetics , Methylation , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Cell Proliferation/genetics
8.
Front Hum Neurosci ; 17: 1253211, 2023.
Article En | MEDLINE | ID: mdl-37727862

Introduction: Speech production involves neurological planning and articulatory execution. How speakers prepare for articulation is a significant aspect of speech production research. Previous studies have focused on isolated words or short phrases to explore speech planning mechanisms linked to articulatory behaviors, including investigating the eye-voice span (EVS) during text reading. However, these experimental paradigms lack real-world speech process replication. Additionally, our understanding of the neurological dimension of speech planning remains limited. Methods: This study examines speech planning mechanisms during continuous speech production by analyzing behavioral (eye movement and speech) and neurophysiological (EEG) data within a continuous speech production task. The study specifically investigates the influence of semantic consistency on speech planning and the occurrence of "look ahead" behavior. Results: The outcomes reveal the pivotal role of semantic coherence in facilitating fluent speech production. Speakers access lexical representations and phonological information before initiating speech, emphasizing the significance of semantic processing in speech planning. Behaviorally, the EVS decreases progressively during continuous reading of regular sentences, with a slight increase for non-regular sentences. Moreover, eye movement pattern analysis identifies two distinct speech production modes, highlighting the importance of semantic comprehension and prediction in higher-level lexical processing. Neurologically, the dual pathway model of speech production is supported, indicating a dorsal information flow and frontal lobe involvement. The brain network linked to semantic understanding exhibits a negative correlation with semantic coherence, with significant activation during semantic incoherence and suppression in regular sentences. Discussion: The study's findings enhance comprehension of speech planning mechanisms and offer insights into the role of semantic coherence in continuous speech production. Furthermore, the research methodology establishes a valuable framework for future investigations in this domain.

9.
Chem Sci ; 14(36): 9933-9942, 2023 Sep 20.
Article En | MEDLINE | ID: mdl-37736631

The ability of Adenosine Triphosphate (ATP) to modulate protein solubility establishes a critical link between ATP homeostasis and proteinopathies, such as Parkinson's (PD). The most significant risk factor for PD is aging, and ATP levels decline dramatically with age. However, the mechanism by which ATP interacts with alpha-synuclein (αS), whose aggregation is characteristic of PD, is currently not fully understood, as is ATP's effect on αS aggregation. Here, we use nuclear magnetic resonance spectroscopy as well as fluorescence, dynamic light scattering and microscopy to show that ATP affects multiple species in the αS self-association cascade. The triphosphate moiety of ATP disrupts long-range electrostatic intramolecular contacts in αS monomers to enhance initial aggregation, while also inhibiting the formation of late-stage ß-sheet fibrils by disrupting monomer-fibril interactions. These effects are modulated by magnesium ions and early onset PD-related αS mutations, suggesting that loss of the ATP hydrotropic function on αS fibrillization may play a role in PD etiology.

10.
Eur J Med Res ; 28(1): 264, 2023 Aug 03.
Article En | MEDLINE | ID: mdl-37537658

Premature ovarian failure (POF) is defined by amenorrhea, ovarian atrophy, hypoestrogenism, elevated gonadotropin level, and infertility under the age of 40. POF is frequently induced by chemotherapeutic agents. However, the underlying mechanisms regarding chemotherapy-mediated damage to ovarian function are unclear. In this study, enhanced apoptosis of granulosa cells (GCs) and aberrant activation of primordial follicles were observed in a POF mouse model induced by cisplatin. We subsequently observed significant downregulation of miR-144-3p and upregulation of mitogen-activated protein kinase kinase kinase 9 (MAP3K9) in primary ovarian GCs from POF mice, as revealed by microarrays. Furthermore, MAP3K9 expression was higher in human ovarian granulosa cells (COV434) treated with cisplatin and was identified as a novel target of miR-144-3p. Functional analysis revealed that miR-144-3p attenuated cisplatin induced apoptosis of GCs via silencing MAP3K9 expression, which suppressed the activity of the downstream p38 mitogen activated protein kinase (MAPK) pathway. Meanwhile, miR-144-3p prevented premature primordial follicle depletion in cisplatin-induced POF mice through targeting Map3k9, which led to a decline in the phosphorylation and activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase b (AKT) pathway. Taken together, this study revealed the protective effects of miR-144-3p on ovarian function and shed light on the epigenetic regulatory mechanism in the development of POF, which might provide new biomarkers for the ovarian reserve.


Antineoplastic Agents , MicroRNAs , Primary Ovarian Insufficiency , Animals , Female , Humans , Mice , Antineoplastic Agents/pharmacology , Apoptosis , Cisplatin/adverse effects , Granulosa Cells/metabolism , MAP Kinase Kinase Kinases/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Primary Ovarian Insufficiency/chemically induced , Primary Ovarian Insufficiency/genetics , Primary Ovarian Insufficiency/prevention & control
11.
Eur J Neurosci ; 58(6): 3503-3517, 2023 09.
Article En | MEDLINE | ID: mdl-37547942

Visual context modulates perception of local orientation attributes. These spatially very localised effects are considered to correspond to specific excitatory-inhibitory connectivity patterns of early visual areas as V1, creating perceptual tilt repulsion and attraction effects. Here, orientation misperception of small Gabor stimuli was used as a probe of this computational structure by sampling a large spatio-orientation space to reveal expected asymmetries due to the underlying neuronal processing. Surprisingly, the results showed a regular iso-orientation pattern of nearby location effects whose reference point was globally modulated by the spatial structure, without any complex interactions between local positions and orientation. This pattern of results was confirmed by the two perceptual parameters of bias and discrimination ability. Furthermore, the response times to stimulus configuration displayed variations that further provided evidence of how multiple early visual stages affect perception of simple stimuli.


Neurons , Orientation , Photic Stimulation/methods , Orientation/physiology , Neurons/physiology , Reaction Time/physiology , Perception , Visual Perception/physiology , Space Perception/physiology
12.
Animals (Basel) ; 13(13)2023 Jun 30.
Article En | MEDLINE | ID: mdl-37443959

pH was one of the important meat quality traits, which was an important factor affecting the storage/shelf life and quality of meat in meat production. In order to find a way to extend the storage/shelf life, the pH values (pH45min, pH24h, pH48h and pH72h) of the longissimus dorsi muscles in F2 individuals of 462 Texel sheep × Altay sheep were determined, genotyping was performed using Illumina Ovine SNP 600 K BeadChip and whole genome resequencing technology, a genome-wide association analysis (GWAS) was used to screen the candidate genes and molecular markers for pH values related to the quality traits of mutton, and the effects of population stratification were detected by Q-Q plots. The results showed that the pH population stratification analysis did not find significant systemic bias, and there was no obvious population stratification effect. The results of the association analysis showed that 28 SNPs significantly associated with pH reached the level of genomic significance. The candidate gene associated with pH45min was identified as the CCDC92 gene by gene annotation and a search of the literature. Candidate genes related to pH24h were KDM4C, TGFB2 and GOT2 genes. The candidate genes related to pH48h were MMP12 and MMP13 genes. The candidate genes related to pH72h were HILPDA and FAT1 genes. Further bioinformatics analyses showed 24 gene ontology terms and five signaling pathways that were significantly enriched (p ≤ 0.05). Many terms and pathways were related to cellular components, processes of protein modification, the activity of protein dimerization and hydrolase activity. These identified SNPs and genes could provide useful information about meat and the storage/shelf life of meat, thereby extending the storage/shelf life and quality of meat.

13.
J Am Chem Soc ; 145(26): 14539-14547, 2023 Jul 05.
Article En | MEDLINE | ID: mdl-37345976

Copolymerization of elemental sulfur (S8) with vinyl monomers to develop new polymer materials is significant. Here, for the first time, we report the anionic hybrid copolymerization of S8 with acrylate at 25 °C, yielding a copolymer with short polysulfide segments; i.e., each of them consists of only one to four sulfur atoms. The formation of a longer polysulfide segment would be ceaselessly disrupted by carbon anions through the chain-transfer reaction. The copolymer of S8 with diacrylate was cross-linked and exhibited excellent mechanical properties, with an ultimate tensile strength as high as 10.7 MPa and a breaking strain of 22%. Furthermore, the introduction of tertiary amide groups to the copolymer enabled it not only to be reprocessed via press molding at room temperature but also to exhibit self-healing properties without external intervention. This study provides a facile strategy to synthesize high-performance sulfur-based copolymers under mild conditions.

14.
Front Microbiol ; 14: 1135700, 2023.
Article En | MEDLINE | ID: mdl-37168119

In the production process of puree cans such as chestnuts cans, it is easy to browning due to excessive heating, which causes a lot of waste every year. The heat and mass transfer model of Chinese Chestnut Puree was established through the finite element method. The model simulated the change process of the temperature field, heat flow velocity field and F value during the production of Chinese Chestnut Puree. After comparing and confirming the effectiveness of the model through the thermal penetration test, the model was used to adjust and optimize the production process. For #9121 cans, the two-stage sterilization method was adopted. Through the sterilization method at 10-65-48-14/118-110°C, a sterilization effect equivalent to that of the original process at 10-86-24/121°C was achieved, the browning problem of the product was alleviated, and the product quality was improved. This practice can also provide a reference for canning enterprises to adjust their production processes in the future.

15.
Opt Express ; 31(10): 15697-15711, 2023 May 08.
Article En | MEDLINE | ID: mdl-37157664

We study the multiple-photon bundle emission in the n-photon Jaynes-Cummings model composed of a two-level system coupled to a single-mode optical field via the n-photon exciting process. Here, the two-level system is strongly driven by a near-resonant monochromatic field, and hence the system can work in the Mollow regime, in which a super-Rabi oscillation between the zero-photon state and the n-photon state can take place under proper resonant conditions. We calculate the photon number populations and the standard equal-time high-order correlation functions, and find that the multiple-photon bundle emission can occur in this system. The multiple-photon bundle emission is also confirmed by investigating the quantum trajectories of the state populations and both the standard and generalized time-delay second-order correlation functions for multiple-photon bundle. Our work paves the way towards the study of multiple-photon quantum coherent devices, with potential application in quantum information sciences and technologies.

16.
Front Genet ; 14: 1105689, 2023.
Article En | MEDLINE | ID: mdl-36911401

Background: The development of distant metastasis (DM) results in poor prognosis of breast cancer (BC) patients, however, it is difficult to predict the risk of distant metastasis. Methods: Differentially expressed genes (DEGs) were screened out using GSE184717 and GSE183947. GSE20685 were randomly assigned to the training and the internal validation cohort. A signature was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Gene set enrichment analysis (GSEA) was used for functional analysis. Finally, a nomogram was constructed and calibration curves and concordance index (C-index) were compiled to determine predictive and discriminatory capacity. The clinical benefit of this nomogram was revealed by decision curve analysis (DCA). Finally, we explored the relationships between candidate genes and immune cell infiltration, and the possible mechanism. Results: A signature containing CD74 and TSPAN7 was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Mechanistically, the signature reflect the overall level of immune infiltration in tissues, especially myeloid immune cells. The expression of CD74 and TSPAN7 is heterogeneous, and the overexpression is positively correlated with the infiltration of myeloid immune cells. CD74 is mainly derived from myeloid immune cells and do not affect the proportion of CD8+T cells. Low expression levels of TSPAN7 is mainly caused by methylation modification in BC cells. This signature could act as an independent predictive factor in patients with BC (p = 0.01, HR = 0.63), and it has been validated in internal (p = 0.023, HR = 0.58) and external (p = 0.0065, HR = 0.67) cohort. Finally, we constructed an individualized prediction nomogram based on our signature. The model showed good discrimination in training, internal and external cohort, with a C-index of 0.742, 0.801, 0.695 respectively, and good calibration. DCA demonstrated that the prediction nomogram was clinically useful. Conclusion: A new immune infiltration related signature developed for predicting metastatic risk will improve the treatment and management of BC patients.

17.
Int J Surg ; 109(5): 1271-1280, 2023 May 01.
Article En | MEDLINE | ID: mdl-36999783

INTRODUCTION: Cervical spine fractures with severe spinal cord injury (SCI) are common following cervical spine trauma and are associated with a high mortality rate. Understanding the mortality patterns of patients with cervical spine fractures and severe SCI can offer valuable evidence to surgeons and family members who are required to make critical healthcare decisions. The authors aimed to evaluate the instantaneous death risk and conditional survival (CS) of such patients and developed conditional nomograms to account for different periods of survivors and predict the survival rates. METHODS: Their instantaneous death risks were calculated using the hazard function, and the Kaplan-Meier method was used to evaluate the survival rates. Cox regression was used to choose the variables for the construction of the nomograms. The area under the receiver operating characteristic curve and calibration plots were used to validate the performance of the nomograms. RESULTS: The authors finally included 450 patients with cervical spine fractures and severe SCI using propensity score matching. The instantaneous death risk was the highest during the first 12 months after injury. Surgical treatment can help decrease the instantaneous death risk quickly, especially in early-term surgery. The 5-year CS increased constantly from 73.3% at baseline to 88.0% after 2 years of survival. Conditional nomograms were constructed at baseline and in those who survived for 6 and 12 months. The area under the receiver operating characteristic curve and calibration curves indicated that the nomograms had a good performance. CONCLUSION: Their results improve our understanding of the instantaneous death risk of patients in different periods following injury. CS demonstrated the exact survival rate among medium-term and long-term survivors. Conditional nomograms are suitable for different survival periods in predicting the probability of survival. Conditional nomograms help in understanding the prognosis and improve the shared decision-making approaches.


Spinal Cord Injuries , Spinal Fractures , Humans , Nomograms , Retrospective Studies , Prognosis , Spinal Fractures/etiology , Spinal Fractures/surgery , Spinal Cord Injuries/complications , Cervical Vertebrae/injuries
18.
Blood Coagul Fibrinolysis ; 34(1): 33-39, 2023 Jan 01.
Article En | MEDLINE | ID: mdl-36598376

BACKGROUND: Von Willebrand factor (VWF) encodes a secreted glycoprotein involved in primary hemostasis. Genetic mutations in this gene leading to either quantitation or qualitative defects of VWF, result in von Willebrand disease (VWD), an inherited bleeding disorder. METHODS: In this study, two families with VWD were recruited and submitted to a series of clinical and genetic examinations. prothrombin time, activated partial thromboplastin time, thrombin time, factor VIII coagulant activity (FVIII:C), VWF antigen (VWF:Ag), VWF ristocetin cofactor (VWF:RCo) tests were measured in peripheral blood. F8, F9, and VWF genes were sequenced using next-generation sequencing, and Sanger sequencing was used as a validation method. RESULTS: Both families had a child suffered spontaneous bleeding. Patient 1 showed normal VWF:Ag, severely decreased FVIII:C and VWF:RCo. Patient 2 showed severely decreased FVIII:C, VWF:Ag, and VWF:RCo. Compound heterozygous mutations of VWF gene were identified in both patients. Patient 1 had a novel deletion variant c.1910_1932del (p.Gly637AlafsTer5) and a missense variant c.605G>A (p.Arg202Gln). Patient 2 had a novel missense variant c.4817T>A (p.Met1606Lys) and a novel missense variant c.5983C>T (p.Pro1995Ser). CONCLUSIONS: We described clinical and molecular features of VWD caused by compound heterozygous mutations in two Chinese patients. Our results expand the variation spectrum of the VWF gene and deepen the understanding of the relationship between the genotype and clinical characteristics of VWD.


Hemostatics , von Willebrand Diseases , Child , Humans , East Asian People , Factor VIII/genetics , Hemorrhage , von Willebrand Diseases/genetics , von Willebrand Factor/genetics
19.
Carbohydr Polym ; 301(Pt B): 120370, 2023 Feb 01.
Article En | MEDLINE | ID: mdl-36446502

Polyguluronic acid (PG) is a type of polysaccharide found in edible brown seaweeds. This study synthesized a new sulfated saccharide (SOGA) by sulfating PG-derived unsaturated oligoguluronic acid (OGA). The molecular weight and degree of sulfate-group substitution of SOGA were 1.6 kDa and 1.03, respectively. The structures of PG, OGA, and SOGA were elucidated using FT-IR and NMR spectroscopy. Furthermore, the immunomodulatory effects of PG, OGA, and SOGA on LPS-triggered RAW264.7 and BV2 cells were evaluated. SOGA, but not PG or OGA, significantly reduced the LPS-stimulated overproduction of proinflammatory mediators and suppressed the activation of corresponding signalling pathways. Also, SOGA could actively regulate immune balance by inhibiting apoptosis and pyroapoptosis. These results suggested that SOGA is a potential therapeutic agent for the prevention of diseases associated with immune disorders owing to its remarkable immunomodulatory effects, and that sulfate groups in the carbohydrate chain play a crucial role for its bioactivities.


Lipopolysaccharides , Sulfates , Lipopolysaccharides/pharmacology , Spectroscopy, Fourier Transform Infrared , Sulfur Oxides , Immunomodulation
20.
Mater Today Bio ; 18: 100500, 2023 Feb.
Article En | MEDLINE | ID: mdl-36471893

Polymethyl methacrylate (PMMA) bone cement (PBC) is commonly used in orthopaedic surgery. However, polymerization volumetric shrinkage, exothermic injury, and low bioactivity prevent PBC from being an ideal material. The developed expandable P(MMA-AA-St) well overcomes the volumetric shrinkage of PBC. However, its biomechanical properties are unsatisfactory. Herein, graphene oxide (GO), a hydrophilic material with favourable biomechanics and osteogenic capability, was added to P(MMA-AA-St) to optimize its biomechanics and bioactivity. The GO-modified self-expandable P(MMA-AA-St)-GO nanocomposite (PGBCs) exhibited outstanding compressive strength (>70 â€‹MPa), water absorption, and volume expansion, as well as a longer handling time and a reduced setting temperature. The cytocompatibility of PGBCs was superior to that of PBC, as demonstrated by CCK-8 assay, live-dead cell staining, and flow cytometry. In addition, better osteoblast attachment was observed, which could be attributed to the effects of GO. The improved level of osteogenic gene and protein expression further illustrated the improved cell-material interactions between osteoblasts and PGBCs. The results of an in vivo study performed by filling bone defects in the femoral condyles of rabbits with PGBCs demonstrated promising intraoperative handling properties and convenient implantation. Blood testing and histological staining demonstrated satisfactory in vivo biosafety. Furthermore, bone morphological and microarchitecture analyses using bone tissue staining and micro-CT scanning revealed better bone-PGBCs contact and osteogenic capability. The results of this study indicate that GO modification improved the physiochemical properties, cytocompatibility, and osteogenic capability of P(MMA-AA-St) and overcame the drawbacks of PBC, allowing its material derivatives to serve as effective implantable biomaterials.

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