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1.
J Craniofac Surg ; 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38830018

There is currently a lack of scientific bibliometric analyses in the field of Pierre Robin sequence (PRS). Pierre Robin sequence is known for its clinical triad of micrognathia, glossoptosis, airway obstruction, and possible secondary cleft palate. These defects can lead to upper airway obstruction, sleep apnea, feeding difficulties, affect an individual's growth and development, education level, and in severe cases can be life-threatening. Through analysis of literature retrieved from the Web of Science Core Collection (WoSCC) database using Results Analysis and Citation Report and Citespace software, 933 original articles and reviews were included after manual screening. The overall trend for the number of annual publications and citations was increasing. On the basis of the analysis, airway evaluation and treatment, mandibular distraction osteogenesis (MDO), as well as descriptions of PRS characteristics have been the focus of research in this field. In addition, with advances in new technologies such as gene sequencing and expanding understanding of diseases among researchers, research on genetics and etiology related to PRS has become a growing trend.

2.
Int J Nanomedicine ; 19: 5109-5123, 2024.
Article En | MEDLINE | ID: mdl-38846643

Introduction: Lumbar interbody fusion is widely employed for both acute and chronic spinal diseases interventions. However, large incision created during interbody cage implantation may adversely impair spinal tissue and influence postoperative recovery. The aim of this study was to design a shape memory interbody fusion device suitable for small incision implantation. Methods: In this study, we designed and fabricated an intervertebral fusion cage that utilizes near-infrared (NIR) light-responsive shape memory characteristics. This cage was composed of bisphenol A diglycidyl ether, polyether amine D-230, decylamine and iron oxide nanoparticles. A self-hardening calcium phosphate-starch cement (CSC) was injected internally through the injection channel of the cage for healing outcome improvement. Results: The size of the interbody cage is reduced from 22 mm to 8.8 mm to minimize the incision size. Subsequent NIR light irradiation prompted a swift recovery of the cage shape within 5 min at the lesion site. The biocompatibility of the shape memory composite was validated through in vitro MC3T3-E1 cell (osteoblast-like cells) adhesion and proliferation assays and subcutaneous implantation experiments in rats. CSC was injected into the cage, and the relevant results revealed that CSC is uniformly dispersed within the internal space, along with the cage compressive strength increasing from 12 to 20 MPa. Conclusion: The results from this study thus demonstrated that this integrated approach of using a minimally invasive NIR shape memory spinal fusion cage with CSC has potential for lumbar interbody fusion.


Spinal Fusion , Spinal Fusion/instrumentation , Spinal Fusion/methods , Animals , Mice , Rats , Calcium Phosphates/chemistry , Minimally Invasive Surgical Procedures/instrumentation , Minimally Invasive Surgical Procedures/methods , Lumbar Vertebrae/surgery , Rats, Sprague-Dawley , Male , Compressive Strength , Cell Proliferation/drug effects , Bone Cements/chemistry , Smart Materials/chemistry , Cell Adhesion/drug effects
3.
Nat Immunol ; 25(6): 969-980, 2024 Jun.
Article En | MEDLINE | ID: mdl-38831104

Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117L variant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.


Genetic Predisposition to Disease , Lupus Erythematosus, Systemic , Toll-Like Receptor 7 , Lupus Erythematosus, Systemic/genetics , Humans , Animals , Toll-Like Receptor 7/genetics , Toll-Like Receptor 7/metabolism , Mice , Child , Female , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Male , Age of Onset , Genetic Variation , NF-kappa B/metabolism , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Adolescent , THP-1 Cells , Interferon Type I/metabolism
4.
J Craniofac Surg ; 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38838360

There is a current lack of bibliometric analysis in facial bone aging and relevant fields. By providing clear and intuitive references, predictions, and guidance for future research, this study aims to fill the gap in the current field, summarize the related research, and guide the researchers' future work. Literature data were retrieved from the Web of Science Core Collection database. Results Analysis and Citation Report of Web of Science, and CiteSpace software were used to optimize the visualization results, including publication characteristics, disciplines, journals, literature, countries/regions, institutions, authors, research focuses, etc. A total of 277 publications were included after manual screening, and the overall trend of annual publications and citations was increasing. On the basis of the analysis, the characteristics of facial bone aging, aging of facial soft tissue, and facial rejuvenation have been the focuses of research in this field. As stem cell research advances and researchers, deepen their comprehension of facial bone aging, basic scientific research on facial bones has witnessed a growing trend.

5.
IEEE Open J Eng Med Biol ; 5: 404-420, 2024.
Article En | MEDLINE | ID: mdl-38899014

Goal: Augment a small, imbalanced, wound dataset by using semi-supervised learning with a secondary dataset. Then utilize the augmented wound dataset for deep learning-based wound assessment. Methods: The clinically-validated Photographic Wound Assessment Tool (PWAT) scores eight wound attributes: Size, Depth, Necrotic Tissue Type, Necrotic Tissue Amount, Granulation Tissue type, Granulation Tissue Amount, Edges, Periulcer Skin Viability to comprehensively assess chronic wound images. A small corpus of 1639 wound images labeled with ground truth PWAT scores was used as reference. A Semi-Supervised learning and Progressive Multi-Granularity training mechanism were used to leverage a secondary corpus of 9870 unlabeled wound images. Wound scoring utilized the EfficientNet Convolutional Neural Network on the augmented wound corpus. Results: Our proposed Semi-Supervised PMG EfficientNet (SS-PMG-EfficientNet) approach estimated all 8 PWAT sub-scores with classification accuracies and F1 scores of about 90% on average, and outperformed a comprehensive list of baseline models and had a 7% improvement over the prior state-of-the-art (without data augmentation). We also demonstrate that synthetic wound image generation using Generative Adversarial Networks (GANs) did not improve wound assessment. Conclusions: Semi-supervised learning on unlabeled wound images in a secondary dataset achieved impressive performance for deep learning-based wound grading.

6.
Arch Esp Urol ; 77(3): 242-248, 2024 Apr.
Article En | MEDLINE | ID: mdl-38715164

OBJECTIVE: To retrospectively analyse the effects of cinobufotalin capsule combined with zoledronic acid on pain symptoms and clinical efficacy of prostate cancer patients with bone metastases. METHODS: Patients with prostate cancer with bone metastasis admitted to our hospital from January 2021 to December 2022 were selected as study subjects. They were divided into the control group (treated with zoledronic acid) and the combined group (cinobufotalin capsules were added on the control group basis) according to different recorded treatment methods. The efficacies of the two groups after matching, lumbar L1-4 bone mineral density (BMD), serum calcium, serum phosphorus, visual analogue scale (VAS) score and Karnofsky performance status (KPS) score before and after treatment were compared, and adverse reactions were statistically analysed. RESULTS: A total of 102 patients were included in the study, encompassing 52 patients in the combined group and 50 patients in the control group. After 1:1 preference score matching, 64 patients were included in the two groups. No significant difference in baseline data was found between the two groups (p > 0.05). The total effective rate of the combination group was higher than that of the control group (p < 0.05). No significant differences in L1-4 bone mineral density, serum calcium and phosphorus, VAS score and KPS score were observed between the two groups prior to treatment (p > 0.05). After treatment, the L1-4 bone mineral density (BMD) and KPS score of the combined group decreased to less than those of the control group, the VAS score was lower than that of the control group, and the serum calcium and phosphorus level increased but less than that of the control group (p < 0.05). No significant difference in adverse reactions was found between the two groups (p > 0.05). CONCLUSIONS: Cinobufotalin capsule combined with zoledronic acid had ideal efficacy in the treatment of prostate cancer in patients with bone metastasis. This approach could improve their bone density and quality of life, improve their calcium and phosphorus metabolism, reduce their pain symptoms and provide increased safety. It may have an important guiding role in formulating future clinical treatment plans for patients with prostate cancer and bone metastasis.


Bone Density Conservation Agents , Bone Neoplasms , Bufanolides , Prostatic Neoplasms , Zoledronic Acid , Humans , Male , Zoledronic Acid/therapeutic use , Zoledronic Acid/administration & dosage , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/complications , Retrospective Studies , Aged , Bone Density Conservation Agents/therapeutic use , Bone Density Conservation Agents/administration & dosage , Bone Neoplasms/secondary , Bone Neoplasms/drug therapy , Bone Neoplasms/complications , Bufanolides/therapeutic use , Bufanolides/administration & dosage , Middle Aged , Treatment Outcome , Capsules , Drug Therapy, Combination , Cancer Pain/drug therapy
7.
BMC Biotechnol ; 24(1): 36, 2024 May 25.
Article En | MEDLINE | ID: mdl-38796454

BACKGROUND: To establish a strategy for stem cell-related tissue regeneration therapy, human gingival mesenchymal stem cells (hGMSCs) were loaded with three-dimensional (3D) bioengineered Matrigel matrix scaffolds in high-cell density microtissues to promote local tissue restoration. METHODS: The biological performance and stemness of hGMSCs under 3D culture conditions were investigated by viability and multidirectional differentiation analyses. A Sprague‒Dawley (SD) rat full-thickness buccal mucosa wound model was established, and hGMSCs/Matrigel were injected into the submucosa of the wound. Autologous stem cell proliferation and wound repair in local tissue were assessed by histomorphometry and immunohistochemical staining. RESULTS: Three-dimensional suspension culture can provide a more natural environment for extensions and contacts between hGMSCs, and the viability and adipogenic differentiation capacity of hGMSCs were significantly enhanced. An animal study showed that hGMSCs/Matrigel significantly accelerated soft tissue repair by promoting autologous stem cell proliferation and enhancing the generation of collagen fibers in local tissue. CONCLUSION: Three-dimensional cell culture with hydrogel scaffolds, such as Matrigel, can effectively improve the biological function and maintain the stemness of stem cells. The therapeutic efficacy of hGMSCs/Matrigel was confirmed, as these cells could effectively stimulate soft tissue repair to promote the healing process by activating the host microenvironment and autologous stem cells.


Collagen , Drug Combinations , Laminin , Mesenchymal Stem Cells , Proteoglycans , Rats, Sprague-Dawley , Tissue Scaffolds , Wound Healing , Animals , Laminin/chemistry , Proteoglycans/chemistry , Collagen/chemistry , Humans , Rats , Mesenchymal Stem Cells/cytology , Tissue Scaffolds/chemistry , Cell Differentiation , Cell Proliferation , Gingiva/cytology , Cell Culture Techniques, Three Dimensional/methods , Cells, Cultured , Tissue Engineering/methods , Male , Mouth Mucosa/cytology
8.
Cell Biosci ; 14(1): 66, 2024 May 23.
Article En | MEDLINE | ID: mdl-38783336

BACKGROUND: Human patients often experience an episode of serious seizure activity, such as status epilepticus (SE), prior to the onset of temporal lobe epilepsy (TLE), suggesting that SE can trigger the development of epilepsy. Yet, the underlying mechanisms are not fully understood. The low-density lipoprotein receptor related protein (Lrp4), a receptor for proteoglycan-agrin, has been indicated to modulate seizure susceptibility. However, whether agrin-Lrp4 pathway also plays a role in the development of SE-induced TLE is not clear. METHODS: Lrp4f/f mice were crossed with hGFAP-Cre and Nex-Cre mice to generate brain conditional Lrp4 knockout mice (hGFAP-Lrp4-/-) and pyramidal neuron specific knockout mice (Nex-Lrp4-/-). Lrp4 was specifically knocked down in hippocampal astrocytes by injecting AAV virus carrying hGFAP-Cre into the hippocampus. The effects of agrin-Lrp4 pathway on the development of SE-induced TLE were evaluated on the chronic seizure model generated by injecting kainic acid (KA) into the amygdala. The spontaneous recurrent seizures (SRS) in mice were video monitored. RESULTS: We found that Lrp4 deletion from the brain but not from the pyramidal neurons elevated the seizure threshold and reduced SRS numbers, with no change in the stage or duration of SRS. More importantly, knockdown of Lrp4 in the hippocampal astrocytes after SE induction decreased SRS numbers. In accord, direct injection of agrin into the lateral ventricle of control mice but not mice with Lrp4 deletion in hippocampal astrocytes also increased the SRS numbers. These results indicate a promoting effect of agrin-Lrp4 signaling in hippocampal astrocytes on the development of SE-induced TLE. Last, we observed that knockdown of Lrp4 in hippocampal astrocytes increased the extracellular adenosine levels in the hippocampus 2 weeks after SE induction. Blockade of adenosine A1 receptor in the hippocampus by DPCPX after SE induction diminished the effects of Lrp4 on the development of SE-induced TLE. CONCLUSION: These results demonstrate a promoting role of agrin-Lrp4 signaling in hippocampal astrocytes in the development of SE-induced development of epilepsy through elevating adenosine levels. Targeting agrin-Lrp4 signaling may serve as a potential therapeutic intervention strategy to treat TLE.

9.
Conserv Biol ; : e14264, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38563105

Antarctica terrestrial ecosystems are facing the most threats from global climate change, which is altering plant composition greatly. These transformations may cause major reshuffling of soil community composition, including functional traits and diversity, and therefore affect ecosystem processes in Antarctica. We used high-throughput sequencing analysis to investigate soil nematodes under 3 dominant plant functional groups (lichens, mosses, and vascular plants) and bare ground in the Antarctic region. We calculated functional diversity of nematodes based on their diet, life histories, and body mass with kernel density n-dimensional hypervolumes. We also calculated taxonomic and functional beta diversity of the nematode communities based on Jaccard dissimilarity. The presence of plants had no significant effect on the taxonomic richness of nematodes but significantly increased nematode functional richness. The presence of plants also significantly decreased taxonomic beta diversity (homogenization). Only mosses and vascular plants decreased nematode functional beta diversity, which was mostly due to a decreased effect of the richness difference component. The presence of plants also increased the effect of deterministic processes potentially because environmental filtering created conditions favorable to nematodes at low trophic levels with short life histories and small body size. Increasing plant cover in the Antarctic due to climate change may lead to increased diversity of nematode species that can use the scarce resources and nematode taxonomic and functional homogenization. In a future under climate change, community restructuring in the region is possible.


Efectos de la posición taxonómica de las plantas sobre las comunidades de nemátodos del suelo en la Antártida Resumen Los ecosistemas terrestres de la Antártida enfrentan las mayores amenazas del cambio climático global, que está alterando gravemente la composición de plantas. Estas transformaciones pueden provocar una reorganización importante de la composición de la comunidad del suelo, incluyendo atributos y diversidad funcionales, y por lo tanto afectar los procesos ecosistémicos en la Antártida. Utilizamos análisis de secuenciación de alto rendimiento para investigar nemátodos del suelo debajo de tres grupos funcionales de plantas dominantes (líquenes, musgos y plantas vasculares) y de suelo desnudo en la región de la Antártida. Calculamos la diversidad funcional de nemátodos con base en su dieta, historia de vida y masa corporal mediante hipervolúmenes n­dimensionales de densidad del núcleo. También calculamos la diversidad beta taxonómica y funcional de las comunidades de nemátodos con base en la disimilitud de Jacard. La presencia de plantas no tuvo efecto significativo sobre la riqueza taxonómica de nemátodos, pero incrementó su riqueza funcional significativamente. La presencia de plantas también disminuyó la diversidad beta taxonómica (homogenización) significativamente. Solo musgos y plantas vasculares disminuyeron la diversidad beta funcional de nemátodos, lo cual se debió principalmente a un menor efecto del componente de diferencia de riqueza. La presencia de plantas también incrementó el efecto de los procesos determinísticos posiblemente porque el filtrado ambiental creó condiciones favorables para los nemátodos de niveles tróficos inferiores con historias de vida corta y tamaño corporal pequeño. El incremento de la cobertura de plantas en la Antártida debido al cambio climático puede conducir a una mayor diversidad de especies de nemátodos que pueden utilizar los escasos recursos y a la homogenización taxonómica y funcional de los nemátodos. En un futuro bajo el cambio climático, es posible la reestructuración comunitaria en la región.

10.
Plants (Basel) ; 13(8)2024 Apr 20.
Article En | MEDLINE | ID: mdl-38674560

Lotus japonicus, is an important perennial model legume, has been widely used for studying biological processes such as symbiotic nitrogen fixation, proanthocyanidin (PA) biosynthesis, and abiotic stress response. High-quality L. japonicus genomes have been reported recently; however, the genetic basis of genes associated with specific characters including proanthocyanidin distribution in most tissues and tolerance to stress has not been systematically explored yet. Here, based on our previous high-quality L. japonicus genome assembly and annotation, we compared the L. japonicus MG-20 genome with those of other legume species. We revealed the expansive and specific gene families enriched in secondary metabolite biosynthesis and the detection of external stimuli. We suggested that increased copy numbers and transcription of PA-related genes contribute to PA accumulation in the stem, petiole, flower, pod, and seed coat of L. japonicus. Meanwhile, According to shared and unique transcription factors responding to five abiotic stresses, we revealed that MYB and AP2/ERF play more crucial roles in abiotic stresses. Our study provides new insights into the key agricultural traits of L. japonicus including PA biosynthesis and response to abiotic stress. This may provide valuable gene resources for legume forage abiotic stress resistance and nutrient improvement.

12.
Am J Physiol Regul Integr Comp Physiol ; 326(6): R567-R577, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38646812

Postexercise reduction in blood pressure, termed postexercise hypotension (PEH), is relevant for both acute and chronic health reasons and potentially for peripheral cardiovascular adaptations. We investigated the interactive effects of exercise intensity and recovery postures (seated, supine, and standing) on PEH. Thirteen normotensive men underwent a V̇o2max test on a cycle ergometer and five exhaustive constant load trials to determine critical power (CP) and the gas exchange threshold (GET). Subsequently, work-matched exercise trials were performed at two discrete exercise intensities (10% > CP and 10% < GET), with 1 h of recovery in each of the three postures. For both exercise intensities, standing posture resulted in a more substantial PEH (all P < 0.01). For both standing and seated recovery postures, the higher exercise intensity led to larger reductions in systolic [standing: -33 (11) vs. -21 (8) mmHg; seated: -34 (32) vs. -17 (37) mmHg, P < 0.01], diastolic [standing: -18 (7) vs. -8 (5) mmHg; seated: -10 (10) vs. -1 (4) mmHg, P < 0.01], and mean arterial pressures [-13 (8) vs. -2 (4) mmHg, P < 0.01], whereas in the supine recovery posture, the reduction in diastolic [-9 (9) vs. -4 (3) mmHg, P = 0.08) and mean arterial pressures [-7 (5) vs. -3 (4) mmHg, P = 0.06] was not consistently affected by prior exercise intensity. PEH is more pronounced during recovery from exercise performed above CP versus below GET. However, the effect of exercise intensity on PEH is largely abolished when recovery is performed in the supine posture.NEW & NOTEWORTHY The magnitude of postexercise hypotension is greater following the intensity above the critical power in a standing position.


Blood Pressure , Exercise , Post-Exercise Hypotension , Posture , Humans , Male , Exercise/physiology , Adult , Blood Pressure/physiology , Posture/physiology , Post-Exercise Hypotension/physiopathology , Young Adult , Supine Position , Recovery of Function , Standing Position , Sitting Position , Hypotension/physiopathology , Oxygen Consumption
13.
Sci Total Environ ; 924: 171517, 2024 May 10.
Article En | MEDLINE | ID: mdl-38461985

Shrubs have developed various mechanisms for soil phosphorus utilization. Shrub encroachment caused by climate warming alters organic phosphorus mineralization capability by promoting available phosphorus absorption and mediating root exudates. However, few studies have explored how warming regulates the effects of dominant shrubs on soil organic phosphorus mineralization capability. We provide insights into warming, dominant shrub removal, and their interactive effects on the soil organic phosphorus mineralization potential in the Qinghai-Tibetan Plateau. Real-time polymerase chain reaction was used to quantify the soil microbial phosphatase genes (phoC and phoD), which can characterize the soil organic phosphate mineralization potential. We found that warming had no significant effect on the soil organic phosphate-mineralized components (total phosphate, organic phosphate, and available phosphate), genes (phoC and phoD), or enzymes (acid and alkaline phosphatases). Shrub removal negatively influenced the organic phosphate-mineralized components and genes. It significantly decreased soil organic phosphate mineralization gene copy numbers only under warming conditions. Warming increased fungal richness and buffered the effects of shrub removal on bacterial richness and gene copy numbers. However, the change in the microbial community was not the main factor affecting organic phosphate mineralization. We found only phoC copy number had significant correlation to AP. Structural equation modelling revealed that shrub removal and the interaction between warming and shrub removal had a negative direct effect on phoC copy numbers. We concluded that warming increases the negative effect of shrub removal on phosphorus mineralization potential, providing a theoretical basis for shrub encroachment on soil phosphate mineralization under warming conditions.


Bacteria , Phosphorus , Phosphorus/analysis , Soil/chemistry , Phosphates/analysis , Organophosphates , Soil Microbiology
14.
Polymers (Basel) ; 16(6)2024 Mar 11.
Article En | MEDLINE | ID: mdl-38543373

With the policy tilt and increased investment in research and development in the world, new energy vehicle technology continues to progress and the drive motor power density continues to improve, which puts forward higher requirements for the comprehensive performance of the core insulating material enameled wire enamel for drive motors. Polyimide (PI) has excellent electrical insulation properties, and heat resistance is often used to drive the motor winding insulation. To further improve the corona resistance and insulating properties of PI wire enamel varnish, in this paper, firstly, fluorene groups with a rigid conjugated structure were introduced into the molecular chain of the PI film by molecular structure modulation, and then uniformly dispersed alumina nanoclusters (AOCs) were introduced into the PI matrix by using an in situ growth process to inhibit the migration of high-energy electrons. The quantum size effect of the alumina nanoclusters was exploited to synergistically enhance the suppression and scattering of energetic moving electrons by PI-based composite films. The results show that the breakdown field strength of the PI-based composite film (MPI/1.0 vol% AOC) reaches 672.2 kV/mm, and the corona resistance life reaches 7.9 min, which are, respectively, 1.55 and 2.19 times higher than those of the initial PI film. A PI-based composite film with excellent insulating and corona resistance properties was obtained.

15.
Viruses ; 16(3)2024 03 05.
Article En | MEDLINE | ID: mdl-38543765

The efficacy of adeno-associated virus (AAV)-based gene therapy is dependent on effective viral transduction, which might be inhibited by preexisting immunity to AAV acquired from infection or maternal delivery. Anti-AAV neutralizing Abs (NAbs) titer is usually measured by in vitro assay and used for patient enroll; however, this assay could not evaluate NAbs' impacts on AAV pharmacology and potential harm in vivo. Here, we infused a mouse anti-AAV9 monoclonal antibody into Balb/C mice 2 h before receiving 1.2 × 1014 or 3 × 1013 vg/kg of rAAV9-coGAA by tail vein, a drug for our ongoing clinical trials for Pompe disease. The pharmacokinetics, pharmacodynamics, and cellular responses combined with in vitro NAb assay validated the different impacts of preexisting NAbs at different levels in vivo. Sustained GAA expression in the heart, liver, diaphragm, and quadriceps were observed. The presence of high-level NAb, a titer about 1:1000, accelerated vector clearance in blood and completely blocked transduction. The AAV-specific T cell responses tended to increase when the titer of NAb exceeded 1:200. A low-level NAbs, near 1:100, had no effect on transduction in the heart and liver as well as cellular responses, but decreased transduction in muscles slightly. Therefore, we propose to preclude patients with NAb titers > 1:100 from rAAV9-coGAA clinical trials.


Antibodies, Neutralizing , Glycogen Storage Disease Type II , Animals , Mice , Humans , Glycogen Storage Disease Type II/therapy , Genetic Therapy , Liver , Disease Models, Animal , Dependovirus/genetics , Genetic Vectors/genetics , Antibodies, Viral
16.
Adv Mater ; 36(25): e2313845, 2024 Jun.
Article En | MEDLINE | ID: mdl-38452373

The resistance of gels and elastomers increases significantly with tensile strain, which reduces conductive stability and restricts their use in stable and reliable electronics. Here, highly conductive tough hydrogels composed of silver nanowires (AgNWs), liquid metal (LM), and poly(vinyl alcohol) (PVA) are fabricated. The stretch-induced orientations of AgNWs, deformable LM, and PVA nanocrystalline create conductive pathways, enhancing the mechanical properties of the hydrogels, including increased ultimate fracture stress (13-33 MPa), strain (3000-5300%), and toughness (390.9-765.1 MJ m-3). Notably, the electrical conductivity of the hydrogels is significantly improved from 4.05 × 10-3 to 24 S m-1 when stretched to 4200% strain, representing a 6000-fold enhancement. The incorporation of PVA nanocrystalline, deformable LM, and AgNWs effectively mitigates stress concentration at the crack tip, thereby conferring crack propagation insensitivity and fatigue resistance to the hydrogels. Moreover, the hydrogels are designed with a reversible crosslinking network, allowing for water-induced recycling.

17.
Adv Healthc Mater ; 13(15): e2304188, 2024 Jun.
Article En | MEDLINE | ID: mdl-38411375

Intranasal vaccines, unlike injectable vaccines, boost immunity along the respiratory tract; this can significantly limit respiratory virus replication and shedding. There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP366, a nucleoprotein-derived epitope and PA224, a polymerase acidic subunit derived epitope, are bioengineered. These BP-NP366/PA224 can be manufactured at a high yield and are obtained at ≈93% purity, exhibiting ambient-temperature stability. Immunological characterization includes comparing systemic and mucosal immune responses mounted following intramuscular or intranasal immunization. Immunization with BP-NP366/PA224 without adjuvant triggers influenza-specific CD8+ T cell priming and memory CD8+ T cell development. Co-delivery with the adjuvant poly(I:C) significantly boosts the size and functionality of the influenza-specific pulmonary resident memory CD8+ T cell pool. Intranasal, but not intramuscular delivery of BP-NP366/PA224 with poly(I:C), provides protection against influenza virus challenge. Overall, the BP approach demonstrates as a suitable antigen formulation for intranasal delivery toward induction of systemic protective T cell responses against influenza virus.


Administration, Intranasal , Influenza Vaccines , Animals , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , Influenza Vaccines/chemistry , Mice , Memory T Cells/immunology , Influenza A virus/immunology , Epitopes/immunology , Epitopes/chemistry , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/immunology , Female , CD8-Positive T-Lymphocytes/immunology , Mice, Inbred C57BL , Mice, Inbred BALB C
18.
Sci Total Environ ; 917: 170464, 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38290671

The aboveground plant communities are crucial in driving ecosystem functioning, particularly being the primary producers in terrestrial ecosystems. Numerous studies have investigated the impacts of aboveground plant communities on multiple ecosystem functions at α-scale. However, such critical effects have been unexplored at ß-scale and the comparative assessment of the effects and underlying mechanisms of aboveground plant communities on α- and ß-multifunctionality has been lacking. In this study, we examined the effects of aboveground plant communities on soil multifunctionality both at α- and ß-scale in the alpine meadow of the Tibetan Plateau. Additionally, we quantified the direct effects of aboveground plant communities, as well as the indirect effects mediated by changes in biotic and abiotic factors, on soil multifunctionality at both scales. Our findings revealed that: 1) Aboveground plant communities had significantly positive effects on α-multifunctionality whereas, ß-multifunctionality was not affected significantly. 2) Aboveground plant communities directly influence α- and ß-multifunctionality in contrasting ways, with positive and negative effects, respectively. Apart from the direct effects of plant community, we found that soil water content and bacterial ß-diversity serving as the primary predictors for the responses of α- and ß-multifunctionality to the presence of aboveground plant communities, respectively. And ß-soil biodiversity appeared to be a stronger predictor of multifunctionality relative to α-soil biodiversity. Our findings provide novel insights into the drivers of ecosystem multifunctionality at different scales, highlight the importance of maintaining biodiversity at multiple scales and offer valuable knowledge for the maintenance of ecosystem functioning and the restoration of alpine meadow ecosystems.


Biodiversity , Ecosystem , Tibet , Plants , Soil , Grassland
19.
Sci Total Environ ; 916: 170199, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38266729

Herein, the adsorption performance of sulfate ion in water on aluminum nitride nanotube(AlNNT) under the influence of an electric field was investigated using the density functional theory (DFT) calculation method. The model structure stability, adsorption energy, electronic and thermodynamic properties of sulfate ion adsorbed on the surface of AlNNT were studied. The calculation results indicate that sulfate ion reacts with multi-atoms on the surface of AlNNT, forming ionic bonds and undergoing chemical adsorption. As the electric field intensity increases, the adsorption energy and the transfer of electrons from sulfate ion to AlNNT increase, leading to a higher degree of hybridization of atomic orbitals and enhanced multi-atom interactions. Additionally, the thermodynamic data suggests that the adsorption between sulfate ion and AlNNT under electric field can occur spontaneously, the process of which is exothermic. The results of present study are expected to propose a novel method for separation and removal of sulfate pollutants from water.

20.
Mol Neurobiol ; 61(1): 411-422, 2024 Jan.
Article En | MEDLINE | ID: mdl-37615879

Anxiety disorder is one of the most common mental disorders worldwide, affecting nearly 30% of adults. However, its underlying molecular mechanisms are still unclear. Here we subjected mice to chronic restraint stress (CRS), a paradigm known to induce anxiety-like behavior in mice. CRS mice exhibited anxiety-like behavior and reduced synaptic transmission in the medial prefrontal cortex (mPFC). Notably, Wisteria Floribunda agglutinin (WFA) staining showed a reduction of perineuronal nets (PNNs) expression in the mPFC of CRS mice. And the mRNA and protein levels of aggrecan (ACAN), a core component of PNNs, were also reduced. Parallelly, enzymatic digestion of PNNs in the mPFC by injecting Chondroitinase ABC (chABC) resulted in anxiety-like behavior in mice. Fluoxetine (FXT) is a clinically prescribed antidepressant/anxiolytic drug. FXT treatment in CRS mice not only ameliorated their deficits in behavior and synaptic transmissions, but also prevented CRS-induced reduction of PNNs and ACAN expressions. This study demonstrates that proper PNNs level is critical to brain functions, and their decline may serve as a pathological mechanism of anxiety disorders.


Extracellular Matrix , Parvalbumins , Humans , Adult , Mice , Animals , Parvalbumins/metabolism , Extracellular Matrix/metabolism , Aggrecans/metabolism , Anxiety , Synaptic Transmission
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