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1.
Virol Sin ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38997087

ABSTRACT

Norovirus (NoV) infection is a major cause of gastroenteritis worldwide. The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity. To date, there are no approved NoV vaccines for clinical use. Here, we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector, AdC68, carrying the major capsid protein (VP1) of noroviral GI and GII genotypes. Compared to intramuscular (i.m.), intranasal (i.n.), or other prime-boost immunization regimens (i.m. â€‹+ â€‹i.m., i.m. â€‹+ â€‹i.n., i.n. â€‹+ â€‹i.m.), AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3), administered via i.n. â€‹+ â€‹i.n. induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid (BALF) and saliva against the four homologous VP1s in mice. It also significantly stimulated the production of blocking antibodies against the four genotypes. In response to re-stimulation with virus-like particles (VLP)-GI.1, VLP-GII.3, VLP-GII.4, and VLP-GII.17, the quadrivalent vaccine administered according to the i.n. â€‹+ â€‹i.n. regimen effectively triggered specific cell-mediated immune responses, primarily characterized by IFN-γ secretion. Furthermore, the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains, making it a promising vaccine candidate for further development.

2.
Orthop Surg ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982572

ABSTRACT

Intertrochanteric femur fracture is the most common hip fracture in elderly people, and the academic community has reached a consensus that early surgery is imperative. Proximal femoral nail anti-rotation (PFNA) and InterTan are the preferred internal fixation devices for intertrochanteric femur fractures in elderly individuals due to their advantages, such as a short lever arm, minimal stress shielding, and resistance to rotation. However, PFNA is associated with complications such as nail back-out and helical blade cut-out due to stress concentration. As a new internal fixation device for intertrochanteric femur fractures, the proximal femoral biodegradable nail (PFBN) addresses the issue of nail back-out and offers more stable fracture fixation, a shorter lever arm, and stress distribution compared to PFNA and InterTan. Clinical studies have shown that compared to PFNA, PFBNs lead to faster recovery of hip joint function, shorter non-weight-bearing time, and faster fracture healing. This article provides a literature review of the structural characteristics, biomechanical analysis, and clinical studies of PFBNs, aiming to provide a theoretical basis for the selection of internal fixation devices for the treatment of intertrochanteric femur fractures in elderly patients and to improve the quality of life of patients during the postoperative period.

3.
Nat Commun ; 15(1): 6155, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039086

ABSTRACT

Chimeric antigen receptor (CAR) T cells show suboptimal efficacy in acute myeloid leukemia (AML). We find that CAR T cells exposed to myeloid leukemia show impaired activation and cytolytic function, accompanied by impaired antigen receptor downstream calcium, ZAP70, ERK, and C-JUN signaling, compared to those exposed to B-cell leukemia. These defects are caused in part by the high expression of CD155 by AML. Overexpressing C-JUN, but not other antigen receptor downstream components, maximally restores anti-tumor function. C-JUN overexpression increases costimulatory molecules and cytokines through reinvigoration of ERK or transcriptional activation, independent of anti-exhaustion. We conduct an open-label, non-randomized, single-arm, phase I trial of C-JUN-overexpressing CAR-T in AML (NCT04835519) with safety and efficacy as primary and secondary endpoints, respectively. Of the four patients treated, one has grade 4 (dose-limiting toxicity) and three have grade 1-2 cytokine release syndrome. Two patients have no detectable bone marrow blasts and one patient has blast reduction after treatment. Thus, overexpressing C-JUN endows CAR-T efficacy in AML.


Subject(s)
Immunotherapy, Adoptive , Leukemia, Myeloid, Acute , Proto-Oncogene Proteins c-jun , Receptors, Chimeric Antigen , Humans , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Receptors, Chimeric Antigen/metabolism , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/genetics , Immunotherapy, Adoptive/methods , Middle Aged , Male , Female , Proto-Oncogene Proteins c-jun/metabolism , Animals , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Aged , Adult , Cell Line, Tumor , Mice
4.
Gene Ther ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961279

ABSTRACT

Neovascular age-related macular degeneration (nAMD) causes severe visual impairment. Pigment epithelium-derived factor (PEDF), soluble CD59 (sCD59), and soluble fms-like tyrosine kinase-1 (sFLT-1) are potential therapeutic agents for nAMD, which target angiogenesis and the complement system. Using the AAV2/8 vector, two bi-target gene therapy agents, AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59, were generated, and their therapeutic efficacy was investigated in laser-induced choroidal neovascularization (CNV) and Vldlr-/- mouse models. After a single injection, AAV2/8-mediated gene expression was maintained at high levels in the retina for two months. Both AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59 significantly reduced CNV development for an extended period without side effects and provided efficacy similar to two injections of current anti-vascular endothelial growth factor monotherapy. Mechanistically, these agents suppressed the extracellular signal-regulated kinase and nuclear factor-κB pathways, resulting in anti-angiogenic activity. This study demonstrated the safety and long-lasting effects of AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59 in CNV treatment, providing a promising therapeutic strategy for nAMD.

5.
Clin Immunol ; 266: 110329, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39067679

ABSTRACT

Overwhelming evidence has shown that aging is a significant risk factor for COVID-19-related hospitalizations, death and other adverse health outcomes. Particular T cell subsets that susceptible to aging and associated with COVID-19 disease severity requires further elucidation. Our study recruited 57 elderly patients with acute COVID-19 and 27 convalescent donors. Adaptive immunity was assessed across the COVID-19 severity spectrum. Patients underwent age-dependent CD4+ T lymphopenia, preferential loss of circulating T follicular regulatory cells (cTfh) subsets including cTfh-em, cTfh-cm, cTfh1, cTfh2, cTfh17 and circulating T follicular regulatory cells (cTfr), which regulated antibody production through different pathways and correlated with COVID-19 severity, were observed. Moreover, vaccination improved cTfh-cm, cTfh2, cTfr proportion and promoted NAb production. In conclusion, the elderly had gone through age-dependent cTfh subsets deficiency, which impeded NAb production and enabled aggravation of COVID-19 to critical illness, whereas SARS-CoV-2 vaccine inoculation helped to rejuvenate cTfh, cTfr and intensify NAb responses.

6.
J Am Chem Soc ; 146(30): 21017-21024, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39029108

ABSTRACT

The devastating COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made society acutely aware of the urgency in developing effective techniques to timely monitor the outbreak of previously unknown viral species as well as their mutants, which could be even more lethal and/or contagious. Here, we report a fluorogenic sensor array consisting of peptides truncated from the binding domain of human angiotensin-converting enzyme 2 (hACE2) for SARS-CoV-2. A set of five fluorescently tagged peptides were used to construct the senor array in the presence of different low-dimensional quenching materials. When orthogonally incubated with the wild-type SARS-CoV-2 and its variants of concern (VOCs), the fluorescence of each peptide probe was specifically recovered, and the different recovery rates provide a "fingerprint" characteristic of each viral strain. This, in turn, allows them to be differentiated from each other using principal component analysis. Interestingly, the classification result from our sensor array agrees well with the evolutionary relationship similarity of the VOCs. This study offers insight into the development of effective sensing tools for highly contagious viruses and their mutants based on rationally truncating peptide ligands from human receptors.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Fluorescent Dyes , Peptides , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/chemistry , SARS-CoV-2/enzymology , SARS-CoV-2/isolation & purification , Humans , Peptides/chemistry , Peptides/metabolism , Fluorescent Dyes/chemistry , COVID-19/virology , COVID-19/diagnosis , Biosensing Techniques/methods
7.
Clin Chem Lab Med ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38860968

ABSTRACT

OBJECTIVES: Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by homozygous deletion and compound heterozygous mutations in survival motor neuron 1 (SMN1), with severity tied to the copy number of survival motor neuron 2 (SMN2). This study aimed to develop a rapid and comprehensive method for the diagnosis of SMA. METHODS: A total of 292 children with clinically suspected SMA and 394 family members were detected by the amplification refractory mutation system polymerase chain reaction-capillary electrophoresis (ARMS-PCR-CE) method, which targeted 19 reported mutations, and the results were compared with those in multiplex ligation-dependent probe amplification (MLPA). Individuals with identified point mutations were further confirmed by SMN1 long-range PCR and Sanger sequencing. RESULTS: A total of 202 children with SMA, 272 carriers, and 212 normal individuals were identified in this study. No difference was found in the R-value distribution of exons 7 and 8 in SMN1 and SMN2 among these cohorts, with coefficients of variation consistently below 0.08. To detect exon 7 and 8 copy numbers in SMN1 and SMN2, the ARMS-PCR-CE results were concordant with those of MLPA. Approximately 4.95 % (10/202) of the study patients had compound heterozygous mutations. CONCLUSIONS: The ARMS-PCR-CE assay is a comprehensive, rapid, and accurate diagnostic method for SMA that simultaneously detects copy numbers of exons 7 and 8 in SMN1/SMN2, as well as 19 point mutations in SMN1 and 2 enhancers in SMN2. This approach can effectively reduce the time frame for diagnosis, facilitating early intervention and preventing birth defects.

8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(3): 511-519, 2024 Jun 25.
Article in Chinese | MEDLINE | ID: mdl-38932537

ABSTRACT

In response to the issues of single-scale information loss and large model parameter size during the sampling process in U-Net and its variants for medical image segmentation, this paper proposes a multi-scale medical image segmentation method based on pixel encoding and spatial attention. Firstly, by redesigning the input strategy of the Transformer structure, a pixel encoding module is introduced to enable the model to extract global semantic information from multi-scale image features, obtaining richer feature information. Additionally, deformable convolutions are incorporated into the Transformer module to accelerate convergence speed and improve module performance. Secondly, a spatial attention module with residual connections is introduced to allow the model to focus on the foreground information of the fused feature maps. Finally, through ablation experiments, the network is lightweighted to enhance segmentation accuracy and accelerate model convergence. The proposed algorithm achieves satisfactory results on the Synapse dataset, an official public dataset for multi-organ segmentation provided by the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), with Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95) scores of 77.65 and 18.34, respectively. The experimental results demonstrate that the proposed algorithm can enhance multi-organ segmentation performance, potentially filling the gap in multi-scale medical image segmentation algorithms, and providing assistance for professional physicians in diagnosis.


Subject(s)
Algorithms , Image Processing, Computer-Assisted , Humans , Image Processing, Computer-Assisted/methods , Diagnostic Imaging/methods , Neural Networks, Computer
9.
Front Oncol ; 14: 1355643, 2024.
Article in English | MEDLINE | ID: mdl-38651157

ABSTRACT

Background: The low rates of durable response against relapsed/refractory multiple myeloma (RRMM) in recent studies prompt that chimeric antigen receptor (CAR)-T cell therapies are yet to be optimized. The combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high clinical efficacy in several clinical trials for RRMM. We here conducted a meta-analysis to confirm its efficacy and safety. Methods: We collected data from Embase, Web of Science, PubMed, CNKI, Wanfang and Cochrane databases up to April 2023. We extracted and evaluated data related to the efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapies in RRMM patients. The data was then analyzed using RevMan5.4 and StataSE-64 software. PROSPERO number was CRD42023455002. Results: Our meta-analysis included 12 relevant clinical trials involving 347 RRMM patients who were treated with combined anti-BCMA and anti-CD19 CAR-T cell therapies. For efficacy assessment, the pooled overall response rate (ORR) was 94% (95% CI: 91%-98%), the complete response rate (CRR) was 50% (95% CI: 29%-71%), and the minimal residual disease (MRD) negativity rate within responders was 73% (95% CI: 66%-80%). In terms of safety, the pooled all-grade cytokine release syndrome (CRS) rate was 98% (95% CI: 97%-100%), grade≥3 CRS rate was 9% (95% CI: 4%-14%), and the incidence of neurotoxicity was 8% (95% CI: 4%-11%). Of hematologic toxicity, neutropenia was 82% (95% CI: 75%-89%), anemia was 71% (95% CI: 53%-90%), thrombocytopenia was 67% (95% CI: 40%-93%) and infection was 42% (95% CI: 9%-76%). The median progression-free survival (PFS) was 12.97 months (95% CI: 6.02-19.91), and the median overall survival (OS) was 26.63 months (95% CI: 8.14-45.11). Conclusions: As a novel immunotherapy strategy with great potential, the combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high efficacy in RRMM, but its safety needs further improvement. This meta-analysis suggests possible optimization of combined CAR-T therapy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023455002.

10.
BMC Neurol ; 24(1): 93, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38468256

ABSTRACT

BACKGROUND: Spinal muscular atrophy (SMA) is a rare autosomal recessive hereditary neuromuscular disease caused by survival motor neuron 1 (SMN1) gene deletion or mutation. Homozygous deletions of exon 7 in SMN1 result in 95% of SMA cases, while the remaining 5% are caused by other pathogenic variants of SMN1. METHODS: We analyzed two SMA-suspected cases that were collected, with no SMN1 gene deletion and point mutation in whole-exome sequencing. Exon 1 deletion of the SMN gene was detected using Multiplex ligation-dependent probe amplification (MLPA) P021. We used long-range polymerase chain reaction (PCR) to isolate the SMN1 template, optimized-MLPA P021 for copy number variation (CNV) analysis within SMN1 only, and validated the findings via third-generation sequencing. RESULTS: Two unrelated families shared a genotype with one copy of exon 7 and a novel variant, g.70919941_70927324del, in isolated exon 1 of the SMN1 gene. Case F1-II.1 demonstrated no exon 1 but retained other exons, whereas F2-II.1 had an exon 1 deletion in a single SMN1 gene. The read coverage in the third-generation sequencing results of both F1-II.1 and F2-II.1 revealed a deletion of approximately 7.3 kb in the 5' region of SMN1. The first nucleotide in the sequence data aligned to the 7385 bp of NG_008691.1. CONCLUSION: Remarkably, two proband families demonstrated identical SMN1 exon 1 breakpoint sites, hinting at a potential novel mutation hotspot in Chinese SMA, expanding the variation spectrum of the SMN1 gene and corroborating the specificity of isolated exon 1 deletion in SMA pathogenesis. The optimized-MLPA P021 determined a novel variant (g.70919941_70927324del) in isolated exon 1 of the SMN1 gene based on long-range PCR, enabling efficient and affordable detection of SMN gene variations in patients with SMA, providing new insight into SMA diagnosis to SMN1 deficiency and an optimized workflow for single exon CNV testing of the SMN gene.


Subject(s)
Multiplex Polymerase Chain Reaction , Muscular Atrophy, Spinal , Humans , DNA Copy Number Variations/genetics , Workflow , Muscular Atrophy, Spinal/diagnosis , Muscular Atrophy, Spinal/genetics , Motor Neurons , Exons/genetics , Survival of Motor Neuron 1 Protein/genetics
11.
NPJ Vaccines ; 9(1): 64, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38509167

ABSTRACT

Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses continue to pose a severe global health burden. Thus, we developed a chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 and influenza virus. When used as a standalone vaccine, intranasal immunization with AdC68-HATRBD induced comprehensive and potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies, and memory T cells, which protected the mice from BA.5.2 and pandemic H1N1 infections. When used as a heterologous booster, AdC68-HATRBD markedly improved the protective immune response of the licensed SARS-CoV-2 or influenza vaccine. Therefore, whether administered intranasally as a standalone or booster vaccine, this combination vaccine is a valuable strategy to enhance the overall vaccine efficacy by inducing robust systemic and mucosal immune responses, thereby conferring dual lines of immunological defenses for these two viruses.

12.
J Funct Biomater ; 15(3)2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38535251

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection caused the COVID-19 pandemic, impacting the global economy and medical system due to its fast spread and extremely high infectivity. Efficient control of the spread of the disease relies on a fast, accurate, and convenient detection system for the early screening of the infected population. Although reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the gold-standard method for SARS-CoV-2 RNA analysis, it has complex experimental procedures and relies on expensive instruments and professional operators. In this work, we proposed a simple, direct, amplification-free lateral flow immunoassay (LFIA) with dual-mode detection of SARS-CoV-2 RNA via direct visualization as well as fluorescence detection. The viral RNA was detected by the designed DNA probes to specifically hybridize with the conserved open reading frame 1ab (ORF1ab), envelope protein (E), and nucleocapsid (N) regions of the SARS-CoV-2 genome to form DNA-RNA hybrids. These hybrids were then recognized by the dual-mode gold nanoparticles (DMNPs) to produce two different readout signals. The fluorescence characteristics of different sizes of GNPs were explored. Under the optimized conditions, the LFIA presented a linear detection range of 104-106 TU/mL with a limit of detection (LOD) of 0.76, 1.83, and 2.58 × 104 TU/mL for lentiviral particles carrying SARS-CoV-2 ORF1ab, E, and N motifs, respectively, in the fluorescent mode, which was up to 10 times more sensitive than the colorimetric mode. Furthermore, the LFIA exhibited excellent specificity to SARS-CoV-2 in comparison with other respiratory viruses. It could be used to detect SARS-CoV-2 in saliva samples. The developed LFIA represents a promising and convenient point-of-care method for dual-mode, rapid detection of SARS-CoV-2, especially in the periods with high infectivity.

15.
Emerg Microbes Infect ; 13(1): 2290838, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38044872

ABSTRACT

Classic chimeric hemagglutinin (cHA) was designed to induce immune responses against the conserved stalk domain of HA. However, it is unclear whether combining more than one HA head domain onto one stalk domain is immunogenic and further induce immune responses against influenza viruses. Here, we constructed numerous novel cHAs comprising two or three fuzed head domains from different subtypes grafted onto one stalk domain, designated as cH1-H3, cH1-H7, cH1-H3-H7, and cH1-H7-H3. The three-dimensional structures of these novel cHAs were modelled using bioinformatics simulations. Structural analysis showed that the intact neutralizing epitopes were exposed in cH1-H7 and were predicted to be immunogenic. The immunogenicity of the cHAs constructs was evaluated in mice using a chimpanzee adenoviral vector (AdC68) vaccine platform. The results demonstrated that cH1-H7 expressed by AdC68 (AdC68-cH1-H7) induced the production of high levels of binding antibodies, neutralizing antibodies, and hemagglutinin inhibition antibodies against homologous pandemic H1N1, drifted seasonal H1N1, and H7N9 virus. Moreover, vaccinated mice were fully protected from a lethal challenge with the aforementioned influenza viruses. Hence, cH1-H7 cHAs with potent immunogenicity might be a potential novel vaccine to provide protection against different subtypes of influenza virus.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A Virus, H7N9 Subtype , Influenza Vaccines , Influenza, Human , Orthomyxoviridae Infections , Animals , Mice , Humans , Influenza Vaccines/genetics , Antibodies, Viral , Influenza A Virus, H1N1 Subtype/genetics , Hemagglutinins , Antibodies, Neutralizing , Hemagglutinin Glycoproteins, Influenza Virus
16.
Nat Commun ; 14(1): 8440, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38114531

ABSTRACT

Autophagy receptor NDP52 triggers bacterial autophagy against infection. However, the ability of NDP52 to protect against viral infection has not been established. We show that NDP52 binds to envelope proteins of hepatitis B virus (HBV) and triggers a degradation process that promotes HBV clearance. Inactivating NDP52 in hepatocytes results in decreased targeting of viral envelopes in the lysosome and increased levels of viral replication. NDP52 inhibits HBV at both viral entry and late replication stages. In contrast to NDP52-mediated bacterial autophagy, lysosomal degradation of HBV envelopes is independent of galectin 8 and ATG5. NDP52 forms complex with Rab9 and viral envelope proteins and links HBV to Rab9-dependent lysosomal degradation pathway. These findings reveal that NDP52 acts as a sensor for HBV infection, which mediates a unique antiviral response to eliminate the virus. This work also suggests direct roles for autophagy receptors in other lysosomal degradation pathways than canonical autophagy.


Subject(s)
Hepatitis B virus , Hepatitis B , Humans , Hepatitis B virus/physiology , Hepatocytes/metabolism , Autophagy/physiology , Lysosomes/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Antiviral Agents/metabolism , Virus Replication/physiology
17.
iScience ; 26(10): 107939, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37810255

ABSTRACT

Neovascular age-related macular degeneration AMD (nAMD) is characterized by choroidal neovascularization (CNV) and could lead to irreversible blindness. However, anti-vascular endothelial growth factor (VEGF) therapy has limited efficacy. Therefore, we generated a chimpanzee adenoviral vector (AdC68-PFC) containing three genes, pigment endothelial-derived factor (PEDF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble forms of CD59 (sCD59), to treat nAMD. The results showed that AdC68-PFC mediated a strong onset of PEDF, sFlt-1, and sCD59 expression both in vivo and in vitro. AdC68-PFC showed preventive and therapeutic effects following intravitreal (IVT) injection in the laser-induced CNV model and very low-density lipoprotein receptor-deficient (Vldlr-/-) mouse model. In vitro assessment indicated that AdC68-PFC had a strong inhibitory effect on endothelial cells. Importantly, the safety test showed no evidence of in vivo toxicity of adenovirus in murine eyes. Our findings suggest that AdC68-PFC may be a long-acting and safe gene therapy vector for future nAMD treatments.

18.
J Virol ; 97(10): e0072423, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37706688

ABSTRACT

IMPORTANCE: The development of broad-spectrum SARS-CoV-2 vaccines will reduce the global economic and public health stress from the COVID-19 pandemic. The use of conserved T-cell epitopes in combination with spike antigen that induce humoral and cellular immune responses simultaneously may be a promising strategy to further enhance the broad spectrum of COVID-19 vaccine candidates. Moreover, this research suggests that the combined vaccination strategies have the ability to induce both effective systemic and mucosal immunity, which may represent promising strategies for maximizing the protective efficacy of respiratory virus vaccines.


Subject(s)
COVID-19 Vaccines , COVID-19 , Vaccines, Combined , Humans , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Immunity, Cellular , Immunization , Pandemics/prevention & control , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination
19.
J Cancer Res Clin Oncol ; 149(17): 15511-15524, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37646827

ABSTRACT

PURPOSE: Skin disease is a prevalent type of physical ailment that can manifest in multitude of forms. Many internal diseases can be directly reflected on the skin, and if left unattended, skin diseases can potentially develop into skin cancer. Accurate and effective segmentation of skin lesions, especially melanoma, is critical for early detection and diagnosis of skin cancer. However, the complex color variations, boundary ambiguity, and scale variations in skin lesion regions present significant challenges for precise segmentation. METHODS: We propose a novel approach for melanoma segmentation using a dual-branch interactive U-Net architecture. Two distinct sampling strategies are simultaneously integrated into the network, creating a vertical dual-branch structure. Meanwhile, we introduce a novel dual-channel symmetrical convolution block (DCS-Conv), which employs a symmetrical design, enabling the network to exhibit a horizontal dual-branch structure. The combination of the vertical and horizontal distribution of the dual-branch structure enhances both the depth and width of the network, providing greater diversity and rich multiscale cascade features. Additionally, this paper introduces a novel module called the residual fuse-and-select module (RFS module), which leverages self-attention mechanisms to focus on the specific skin cancer features and reduce irrelevant artifacts, further improving the segmentation accuracy. RESULTS: We evaluated our approach on two publicly skin cancer datasets, ISIC2016 and PH2, and achieved state-of-the-art results, surpassing previous outcomes in terms of segmentation accuracy and overall performance. CONCLUSION: Our proposed approach holds tremendous potential to aid dermatologists in clinical decision-making.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Skin Neoplasms/diagnostic imaging , Skin , Melanoma/diagnostic imaging , Clinical Decision-Making
20.
Neural Netw ; 165: 491-505, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37336034

ABSTRACT

MicroRNAs (miRNA) play critical roles in diverse biological processes of diseases. Inferring potential disease-miRNA associations enable us to better understand the development and diagnosis of complex human diseases via computational algorithms. The work presents a variational gated autoencoder-based feature extraction model to extract complex contextual features for inferring potential disease-miRNA associations. Specifically, our model fuses three different similarities of miRNAs into a comprehensive miRNA network and then combines two various similarities of diseases into a comprehensive disease network, respectively. Then, a novel graph autoencoder is designed to extract multilevel representations based on variational gate mechanisms from heterogeneous networks of miRNAs and diseases. Finally, a gate-based association predictor is devised to combine multiscale representations of miRNAs and diseases via a novel contrastive cross-entropy function, and then infer disease-miRNA associations. Experimental results indicate that our proposed model achieves remarkable association prediction performance, proving the efficacy of the variational gate mechanism and contrastive cross-entropy loss for inferring disease-miRNA associations.


Subject(s)
MicroRNAs , Humans , MicroRNAs/genetics , Genetic Predisposition to Disease , Algorithms , Computational Biology/methods
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