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1.
PLoS One ; 19(8): e0309029, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39146385

RESUMO

Multi-view stereo based on learning is a critical task in three-dimensional reconstruction, enabling the effective inference of depth maps and the reconstruction of fine-grained scene geometry. However, the results obtained by current popular 3D reconstruction methods are not precise, and achieving high-accuracy scene reconstruction remains challenging due to the pervasive impact of feature extraction and the poor correlation between cost and volume. In addressing these issues, we propose a cascade deep residual inference network to enhance the efficiency and accuracy of multi-view stereo depth estimation. This approach builds a cost-volume pyramid from coarse to fine, generating a lightweight, compact network to improve reconstruction results. Specifically, we introduce the omni-dimensional dynamic atrous spatial pyramid pooling (OSPP), a multiscale feature extraction module capable of generating dense feature maps with multiscale contextual information. The feature maps encoded by the OSPP module can generate dense point clouds without consuming significant memory. Furthermore, to alleviate the issue of feature mismatch in cost volume regularization, we propose a normalization-based 3D attention module. The 3D attention module aggregates crucial information within the cost volume across the dimensions of channel, spatial, and depth. Through extensive experiments on benchmark datasets, notably DTU, we found that the OD-MVSNet model outperforms the baseline model by approximately 1.4% in accuracy loss, 0.9% in completeness loss, and 1.2% in overall loss, demonstrating the effectiveness of our module.


Assuntos
Imageamento Tridimensional , Imageamento Tridimensional/métodos , Algoritmos , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Humanos
2.
Adv Sci (Weinh) ; : e2403362, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39073303

RESUMO

In recent years, negative pressure wound dressings have garnered widespread attentions. However, it is challenging to drain the accumulated fluid under negative pressures for hydrogel dressings. To address this issue, this study prepared a chemical/physical duel-network PEG-CMCS/AG/MXene hydrogel composed by chemical disulfide crosslinked network of four-arm polyethylene glycol/carboxymethyl chitosan (4-Arm-PEG-SH/CMCS), and the physical network of hydrogen bond of agar (AG). Under near-infrared light (NIR) irradiation, the PEG-CMCS/AG/MXene hydrogel undergoes photothermal heating due to integrate of MXene, which destructs the hydrogen bond network and allows the removal of exudate through a mechanism mimicking the sweat gland-like effect of skin pores. The photothermal heating effect also enables the antimicrobial activity to prevent wound infections. The excellent electrical conductivity of PEG-CMCS/AG/MXene can promote cell proliferation under the external electrical stimulation (ES) in vitro. The animal experiments of full-thickness skin defect model further demonstrate its ability to accelerate wound healing. The conversion between thioester and thiol achieved with L-cysteine methyl ester hydrochloride (L-CME) can provides the on-demand dissolution of the dressing in situ. This study holds promises to provide a novel solution to the issue of fluid accumulations under hydrogel dressings and offers new approaches to alleviating or avoiding the significant secondary injuries caused by frequent dressing changes.

3.
Colloids Surf B Biointerfaces ; 242: 114082, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39038412

RESUMO

Hydrogels possess inherent characteristics that render them promising for the prevention of peri-implantitis. Nonetheless, hydrogels with singular network structures are incapable of concurrently achieving the desired adhesion and mechanical properties. In this work, a carboxymethyl resistant starch/polyacrylic acid semi-interpenetrating (CMRS/PAA semi-IPN) hydrogel was successfully prepared in one step. Its morphology, structure, mechanical properties, and adhesion properties were systematically assessed, which revealed a homogeneously porous structure with a commendable mechanical strength of 67.317 kPa and an adhesion strength of 63 kPa. Ciprofloxacin (Cip) was loaded in the CMRS/PAA hydrogel via in situ compounding. The in vitro kinetic study of drug release shows that the slow drug release efficiency exceeds 90 % in the weakly acidic microenvironment at the infection site after 72 h, indicating enhanced antimicrobial properties. The Cip-loaded hydrogel also exhibits a remarkable bacterial inhibition rate exceeding 99 % against the pathogenic bacterium P. gingivalis and good cytocompatibility and hemocompatibility in vitro. In summary, the current work explored a novel solution and direction for the development of anti-infective medical materials applicable to dental implants.

4.
Commun Biol ; 7(1): 784, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951577

RESUMO

Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis.


Assuntos
Química Click , Camundongos Endogâmicos C57BL , Rickettsia , Animais , Rickettsia/genética , Rickettsia/fisiologia , Camundongos , Química Click/métodos , Estômago/microbiologia , Modelos Animais de Doenças , Rickettsiose do Grupo da Febre Maculosa/microbiologia , Feminino , Infecções por Rickettsia/microbiologia , Azidas/química
5.
Sci Rep ; 14(1): 14106, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38890489

RESUMO

Although 3D reconstruction has been widely used in many fields as a key component of environment perception, existing technologies still have the potential for further improvement in 3D scene reconstruction. We propose an improved reconstruction algorithm based on the MVSNet network architecture. To glean richer pixel details from images, we suggest deploying a DE module integrated with a residual framework, which supplants the prevailing feature extraction mechanism. The DE module uses ECA-Net and dilated convolution to expand the receptive field range, performing feature splicing and fusion through the residual structure to retain the global information of the original image. Moreover, harnessing attention mechanisms refines the 3D cost volume's regularization process, bolstering the integration of information across multi-scale feature volumes, consequently enhancing depth estimation precision. When assessed our model using the DTU dataset, findings highlight the network's 3D reconstruction scoring a completeness (comp) of 0.411 mm and an overall quality of 0.418 mm. This performance is higher than that of traditional methods and other deep learning-based methods. Additionally, the visual representation of the point cloud model exhibits marked advancements. Trials on the Blended MVS dataset signify that our network exhibits commendable generalization prowess.

6.
J Med Virol ; 96(6): e29711, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38847304

RESUMO

The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.


Assuntos
Genoma Viral , Filogenia , Infecções Respiratórias , Humanos , China/epidemiologia , Genoma Viral/genética , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Sistema Respiratório/virologia , Pré-Escolar , Adulto , Criança , RNA Viral/genética , Pessoa de Meia-Idade
7.
Indian J Orthop ; 58(5): 587-597, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38694692

RESUMO

Background: Lumbar disc herniation is a common degenerative lumbar disease with an increasing incidence. Percutaneous endoscopic lumbar discectomy can treat lumbar disc herniation safely and effectively with a minimally invasive procedure. However, the learning curve of this technology is steep, which means that initial learners are often not sufficiently proficient in endoscopic operations, which can easily lead to iatrogenic damage. At present, the application of computer deep learning technology to clinical diagnosis, treatment, and surgical navigation has achieved satisfactory results. Purpose: The objective of our team is to develop a multi-element identification system for the visual field of endoscopic spine surgery using deep learning algorithms and to evaluate the feasibility of this system. Method: We established an image database by collecting surgical videos of 48 patients diagnosed with lumbar disc herniation, which was labeled by two spinal surgeons. We selected 6000 images of the visual field of percutaneous endoscopic spine surgery (including various tissue structures and surgical instruments), divided into the training data, validation data, and test data according to 2:1:2. We developed convolutional neural network models based on instance segmentation-Solov2, CondInst, Mask R-CNN and Yolact, and set the four network model backbone as ResNet101 and ResNet50 respectively. Mean average precision (mAP) and frames per second (FPS) were used to measure the performance of each model for classification, localization and recognition in real time, and AP (average) is used to evaluate how easily an element is detected by neural networks based on computer deep learning. Result: Comprehensively comparing mAP and FSP of each model for bounding box test and segmentation task for the test set of images, we found that Solov2 (ResNet101) (mAP = 73.5%, FPS = 28.9), Mask R-CNN (ResNet101) (mAP = 72.8%, FPS = 28.5) models are the most stable, with higher precision and faster image processing speed. Combining the average precision of the elements in the bounding box test and segmentation tasks in each network, the AP(average) was highest for tool 3 (bbox-0.85, segm-0.89) and lowest for tool 5 (bbox-0.63, segm-0.72) in the instrumentation, whereas in the anatomical tissue elements, the fibrosus annulus (bbox-0.68, segm-0.69) and ligamentum flavum (bbox-0.65, segm-0.62) had higher AP(average),while extra-dural fat (bbox-0.42, segm-0.44) was lowest. Conclusion: Our team has developed a multi-element identification system for the visual field of percutaneous endoscopic spine surgery adapted to the interlaminar and foraminal approaches, which can identify and track anatomical tissue (nerve, ligamentum flavum, nucleus pulposus, etc.) and surgical instruments (endoscopic forceps, an high-speed diamond burr, etc.), which can be used in the future as a virtual educational tool or applied to the intraoperative real-time assistance system for spinal endoscopic operation.

8.
Arch Microbiol ; 206(5): 232, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38658486

RESUMO

Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria.


Assuntos
Anti-Inflamatórios não Esteroides , Biotransformação , Ibuprofeno , Naproxeno , Ibuprofeno/metabolismo , Naproxeno/metabolismo , Anti-Inflamatórios não Esteroides/metabolismo , Biodegradação Ambiental
9.
Virus Res ; 345: 199378, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38643857

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to human health globally. It is crucial to develop a vaccine to reduce the effect of the virus on public health, economy, and society and regulate the transmission of SARS-CoV-2. Influenza B virus (IBV) can be used as a vector that does not rely on the current circulating influenza A strains. In this study, we constructed an IBV-based vector vaccine by inserting a receptor-binding domain (RBD) into a non-structural protein 1 (NS1)-truncated gene (rIBV-NS110-RBD). Subsequently, we assessed its safety, immunogenicity, and protective efficacy against SARS-CoV-2 in mice, and observed that it was safe in a mouse model. Intranasal administration of a recombinant rIBV-NS110-RBD vaccine induced high levels of SARS-CoV-2-specific IgA and IgG antibodies and T cell-mediated immunity in mice. Administering two doses of the intranasal rIBV-NS110-RBD vaccine significantly reduced the viral load and lung damage in mice. This novel IBV-based vaccine offers a novel approach for controlling the SARS-CoV-2 pandemic.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Vírus da Influenza B , Camundongos Endogâmicos BALB C , SARS-CoV-2 , Vacinas Atenuadas , Animais , Camundongos , Vírus da Influenza B/imunologia , Vírus da Influenza B/genética , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Administração Intranasal , Humanos , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Imunoglobulina A/sangue , Modelos Animais de Doenças , Imunoglobulina G/sangue , Carga Viral , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia
10.
Heliyon ; 10(6): e27631, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545199

RESUMO

Long noncoding RNA small nucleolar RNA host gene 1 (lncRNA SNHG1) plays a crucial role in the occurrence and progression of various tumors. This study investigates the function of lncRNA SNHG1 in hepatocellular carcinoma (HCC). We discovered that lncRNA SNHG1 is significantly upregulated in HCC and markedly enhances cell proliferation, migration, and invasion, while simultaneously suppressing apoptosis in HCC cells. Furthermore, lncRNA SNHG1 was found to downregulate miR-7-5p expression. Overexpression of lncRNA SNHG1 counteracted the suppression of HCC cell migration, proliferation, and invasion caused by miR-7-5p mimics, and reversed the miR-7-5p mimics' enhancement of apoptosis in HCC cells. Additionally, miR-7-5p was shown to negatively regulate IGF2BP2, with the silencing of IGF2BP2 diminishing the abilities of HCC cells to proliferate, migrate, and invade, and increasing their propensity for apoptosis. Overexpression of lncRNA SNHG1 negated these effects. Thus, lncRNA SNHG1 fosters HCC progression by upregulating IGF2BP2 expression through targeting miR-7-5p.

11.
Sensors (Basel) ; 24(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38474902

RESUMO

Underwater optical imaging for information acquisition has always been an innovative and crucial research direction. Unlike imaging in the air medium, the underwater optical environment is more intricate. From an optical perspective, natural factors such as turbulence and suspended particles in the water cause issues like light scattering and attenuation, leading to color distortion, loss of details, decreased contrast, and overall blurriness. These challenges significantly impact the acquisition of underwater image information, rendering subsequent algorithms reliant on such data unable to function properly. Therefore, this paper proposes a method for underwater image restoration using Stokes linearly polarized light, specifically tailored to the challenges of underwater complex optical imaging environments. This method effectively utilizes linear polarization information and designs a system that uses the information of the first few frames to calculate the enhanced images of the later frames. By doing so, it achieves real-time underwater Stokes linear polarized imaging while minimizing human interference during the imaging process. Furthermore, the paper provides a comprehensive analysis of the deficiencies observed during the testing of the method and proposes improvement perspectives, along with offering insights into potential future research directions.

12.
Anal Chem ; 96(11): 4369-4376, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38447031

RESUMO

The oxygen isotope composition of phosphate is a useful tool for studying biogeochemical phosphorus cycling. However, the current Ag3PO4 method is not only tedious in PO43- extraction and purification but also requires a large-sized sample at the micromole level, thereby limiting its application. Here, we present an approach to measuring the oxygen isotope composition, δ18O, of dissolved phosphate at the nanomole level using electrospray ionization Orbitrap mass spectrometry (ESI-Orbitrap-MS). We compared the reproducibility of δ18O measurements using the H2PO4- ions (m/z = 97 and 99 for H2P16O4- and H2P18O16O3-, respectively) and using the PO3- fragment ions (m/z = 79 and 81 for P16O3- and P18O16O2-, respectively) generated by source fragmentation and by higher-energy collisional dissociation, respectively. The results demonstrate that phosphate δ18O can be more reliably measured by the PO3- ions than by the H2PO4- ions. PO3- generated by source fragmentation at 40 V achieved the highest reproducibility for δ18O based on precision tests. Furthermore, the mass spectrum for a 50:50 µM mixed solution of phosphate and sulfate revealed that PO3- ions resulting from source fragmentation at 40 V are the predominant species in the Orbitrap analyzer. Notably, P16O3- ions (m/z: 79) are not interfered with by 32S16O3- (m/z: 80) ions. This is in contrast to the case for 1H2P16O4- ions, which share the same m/z value with 1H32S16O4- ions and exhibit much lower signal intensity than HSO4- ions. Using the PO3- fragment method and six phosphate standards with a wide range of δ18O values, we obtained a calibration line with a slope of 0.94 (R2 = 0.98). The overall uncertainty for ESI-Orbitrap-MS phosphate δ18O measurement was 0.8‰ (n = 30; 1 SD). With much room for improvement, the PO3- fragment method presents a better approach to measuring the phosphate oxygen isotope composition, applicable to nanomole sample sizes in a liquid phase.

13.
Sci China Life Sci ; 67(7): 1502-1513, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38478297

RESUMO

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Camundongos Transgênicos , Pangolins , SARS-CoV-2 , Animais , Humanos , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , SARS-CoV-2/patogenicidade , SARS-CoV-2/genética , COVID-19/virologia , Pangolins/virologia , Camundongos , Replicação Viral , Pulmão/virologia , Pulmão/patologia , Chlorocebus aethiops , Células Vero
14.
J Pain Res ; 17: 381-392, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38312505

RESUMO

Objective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients. Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3). Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = -10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = -0.13, sig < 0.05). Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA.

15.
Nat Commun ; 15(1): 1048, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316817

RESUMO

We recently detected a HKU4-related coronavirus in subgenus Merbecovirus (named pangolin-CoV-HKU4-P251T) from a Malayan pangolin1. Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4.


Assuntos
Infecções por Coronavirus , Coronavirus , Pangolins , Animais , Feminino , Humanos , Camundongos , China , Quirópteros , Citocinas , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Camundongos Transgênicos , Pangolins/virologia
16.
Adv Mater ; 36(15): e2309591, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38113900

RESUMO

In osteosarcoma, immunotherapy often faces hurdles posed by cancer-associated fibroblasts (CAFs) that secrete dense extracellular matrix components and cytokines. Directly removing CAFs may prove ineffective and even promote tumor metastasis. To address this challenge, a sequential nanocomposite hydrogel that reshapes CAF behavior is developed, enhancing tumor-infiltrating T-cells in osteosarcoma. The approach utilizes an injectable blend of carboxymethyl chitosan and tetrabasic polyethylene glycol, forming a hydrogel for controlled release of a potent CAF suppressor (Nox4 inhibitor, Nox4i) and liposomal Doxorubicin (L-Dox) to induce immunogenic cell death (ICD) upon in situ administration. Nox4i effectively counters CAF activation, overcoming T-cell exclusion mechanisms, followed by programmed L-Dox release for ICD induction in stroma-rich osteosarcoma models. Combining the co-delivery gel with αPD-1 checkpoint inhibitor further enhances its effectiveness in an orthotopic osteosarcoma model. Immunophenotyping data underscore a significant boost in tumor T-cell infiltration and favorable anti-tumor immunity at the whole-animal level.


Assuntos
Neoplasias Ósseas , Fibroblastos Associados a Câncer , Doxorrubicina/análogos & derivados , Osteossarcoma , Animais , Nanogéis , Fibroblastos Associados a Câncer/patologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Hidrogéis/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Imunoterapia , Linhagem Celular Tumoral , Microambiente Tumoral , Polietilenoglicóis
17.
J Virol ; 97(11): e0110123, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37916835

RESUMO

IMPORTANCE: Clade 2.3.4.4 H5Nx avian influenza viruses (AIVs) have circulated globally and caused substantial economic loss. Increasing numbers of humans have been infected with Clade 2.3.4.4 H5N6 AIVs in recent years. Only a few human influenza vaccines have been licensed to date. However, the licensed live attenuated influenza virus vaccine exhibited the potential of being recombinant with the wild-type influenza A virus (IAV). Therefore, we developed a chimeric cold-adapted attenuated influenza vaccine based on the Clade 2.3.4.4 H5 AIVs. These H5 vaccines demonstrate the advantage of being non-recombinant with circulated IAVs in the future influenza vaccine study. The findings of our current study reveal that these H5 vaccines can induce cross-reactive protective efficacy in mice and ferrets. Our H5 vaccines may provide a novel option for developing human-infected Clade 2.3.4.4 H5 AIV vaccines.


Assuntos
Proteção Cruzada , Vírus da Influenza A , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Camundongos , Anticorpos Antivirais , Furões , Influenza Aviária , Vacinas contra Influenza/genética , Vacinas Atenuadas , Infecções por Orthomyxoviridae/prevenção & controle
18.
Sci Rep ; 13(1): 18353, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884630

RESUMO

Circular RNAs (circRNAs) play key roles in colorectal cancer (CRC) progression, but little is known about the biological functions of hsa_circRNA_001676 in CRC. Therefore, we explored the potential role of hsa_circRNA_001676 in CRC development. RT-qPCR was performed to determine hsa_circRNA_001676, miR-556-3p and Ras-GTPase-activating SH3 domain-binding-proteins 2 (G3BP2) levels in CRC tissues. Meanwhile, to evaluate the roles of hsa_circRNA_001676, miR-556-3p and G3BP2 on CRC, functional analysis of cell proliferation, migration and stemness were then performed. Our results showed that compared to normal tissues, hsa_circRNA_001676 and G3BP2 level was elevated, but miR-556-3p level was reduced in CRC tissues. Additionally, luciferase reporter results showed that hsa_circRNA_001676 was shown to target miR-556-3p, and G3BP2 was targeted by miR-556-3p. Hsa_circRNA_001676 or G3BP2 overexpression promoted CRC cell proliferation and migration. Conversely, miR-556-3p overexpression suppressed CRC cell proliferation and migration. Moreover, deficiency of hsa_circRNA_001676 or G3BP2 repressed the CRC cell proliferation, migration and stemness. Meanwhile, hsa_circRNA_001676 deficiency obviously reduced tumor growth and stemness in a CRC mouse xenograft model. Furthermore, hsa_circRNA_001676 deficiency notably reduced G3BP2 level, but elevated miR-556-3p level in tumor tissues from tumor-bearing mice. Mechanistically, hsa_circRNA_001676 targeted miR-556-3p to increase G3BP2 level, contributing to the progression of CRC. Collectively, hsa_circRNA_001676 was able to accelerate proliferation, migration and stemness in CRC through regulating miR-556-3p/G3BP2 axis, suggesting that hsa_circRNA_001676 may become a potential therapeutic target in treating CRC.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Animais , Camundongos , RNA Circular/genética , MicroRNAs/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/genética , Proteínas Adaptadoras de Transdução de Sinal/genética
19.
Immunobiology ; 228(3): 152355, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36868006

RESUMO

Acute myeloid leukemia (AML) is widely considered an immunoresponsive malignancy. However, potential association between glycolysis-immune related genes and AML patients' prognosis has been seldom studied. AML-related data was downloaded from TCGA and GEO databases. We grouped patients according to Glycolysis status, Immune Score and combination analysis, basing on which overlapped differentially expressed genes (DEGs) were identified. The Risk Score model was then established. The results showed that totally 142 overlapped genes were probably correlated with glycolysis-immunity in AML patients, among which 6 optimal genes were screened to construct Risk Score. High Risk Score was an independent poor prognostic factor for AML. In conclusion, we established a relatively reliable prognostic signature of AML based on glycolysis-immunity related genes, including METTL7B, HTR7, ITGAX, TNNI2, SIX3 and PURG.


Assuntos
Leucemia Mieloide Aguda , Humanos , Prognóstico , Antígeno CD11c , Glicólise , Fatores de Risco
20.
Neurol Sci ; 44(5): 1687-1694, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36653543

RESUMO

BACKGROUND: Limited studies have focused on the risk assessment of stroke in rural regions. Moreover, the application of artificial intelligence in stroke risk scoring system is still insufficient. This study aims to develop a simplified and visualized risk score with good performance and convenience for rural stroke risk assessment, which is combined with a machine learning (ML) algorithm. METHODS: Participants of the Henan Rural Cohort were enrolled in this study. The total participants (n = 38,322) were randomly split into a train set and a test set in the ratio of 7:3. An ML algorithm was used to select variables and the logistic regression was then applied to construct the scoring system. The C-statistic and the Brier score (BS) were used to evaluate the discrimination and calibration. The Framingham stroke risk profile (FSRP) and the self-reported stroke risk function (SRSRF) were chosen to be compared. RESULTS: The Rural Stroke Risk Score (RSRS) was produced in this study, including age, drinking status, triglyceride, type 2 diabetes mellitus, hypertension, waist circumference, and family history of stroke. On validation, the C-statistic was 0.757 (95% CI 0.749-0.765) and the BS was 0.058 in the test set. In addition, the discrimination of RSRS was 6.02% and 7.34% higher than that of the FSRP and SRSRF, respectively. CONCLUSIONS: A well-performed scoring system for assessing stroke risk in rural residents was developed in this study. This risk score would facilitate stroke screening and the prevention of cardiovascular disease in economically underdeveloped areas.


Assuntos
Diabetes Mellitus Tipo 2 , Acidente Vascular Cerebral , Humanos , Inteligência Artificial , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
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