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1.
Front Plant Sci ; 15: 1425103, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239193

RESUMO

Existing seed germination detection technologies based on deep learning are typically optimized for hydroponic breeding environments, leading to a decrease in recognition accuracy in complex soil cultivation environments. On the other hand, traditional manual germination detection methods are associated with high labor costs, long processing times, and high error rates, with these issues becoming more pronounced in complex soil-based environments. To address these issues in the germination process of new cucumber varieties, this paper utilized a Seed Germination Phenotyping System to construct a cucumber germination soil-based experimental environment that is more closely aligned with actual production. This system captures images of cucumber germination under salt stress in a soil-based environment, constructs a cucumber germination dataset, and designs a lightweight real-time cucumber germination detection model based on Real-Time DEtection TRansformer (RT-DETR). By introducing online image enhancement, incorporating the Adown downsampling operator, replacing the backbone convolutional block with Generalized Efficient Lightweight Network, introducing the Online Convolutional Re-parameterization mechanism, and adding the Normalized Gaussian Wasserstein Distance loss function, the training effectiveness of the model is enhanced. This enhances the model's capability to capture profound semantic details, achieves significant lightweighting, and enhances the model's capability to capture embryonic root targets, ultimately completing the construction of the RT-DETR-SoilCuc model. The results show that, compared to the RT-DETR-R18 model, the RT-DETR-SoilCuc model exhibits a 61.2% reduction in Params, 61% reduction in FLOP, and 56.5% reduction in weight size. Its mAP@0.5, precision, and recall rates are 98.2%, 97.4%, and 96.9%, respectively, demonstrating certain advantages over the You Only Look Once series models of similar size. Germination tests of cucumbers under different concentrations of salt stress in a soil-based environment were conducted, validating the high accuracy of the RT-DETR-SoilCuc model for embryonic root target detection in the presence of soil background interference. This research reduces the manual workload in the monitoring of cucumber germination and provides a method for the selection and breeding of new cucumber varieties.

2.
Front Med (Lausanne) ; 11: 1445752, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39238596

RESUMO

Background: Lung cancer associated with cystic airspaces is a rare disease, and a rare imaging performance of non-small cell lung cancer. Due to the lack of conventional diagnosis methods, it is difficult to rely on imaging diagnosis. Therefore, the definitive diagnosis of these neoplastic lesions remains challenging. Case presentation: We summarize the follow-up and diagnosis of a rare cystic airspaces lung metastatic carcinoma in an elderly man with annular density shadow in the right inferior lobe 2 years after surgery for squamous cell carcinoma in the left inferior lobe. Results: During the follow-up of the patient, after the lesion of the lower lobe of the right lung was enlarged, the structural and imaging characteristics were identified, and a special method was selected, namely biopsy of the lesion under the electromagnetic navigation bronchoscope, for clear diagnosis and subsequent treatment. Conclusion: For pulmonary cystic airspaces, it is important to correctly identify their imaging features. Because of the possibility of malignancy, it is essential to stop the radiological study in time and to acquire the pathological diagnosis by an appropriate method.

3.
Sci Rep ; 14(1): 20220, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39215016

RESUMO

Researchers have investigated the potential of leveraging pre-trained language models, such as CodeBERT, to enhance source code-related tasks. Previous methodologies have relied on CodeBERT's '[CLS]' token as the embedding representation of input sequences for task performance, necessitating additional neural network layers to enhance feature representation, which in turn increases computational expenses. These approaches have also failed to fully leverage the comprehensive knowledge inherent within the source code and its associated text, potentially limiting classification efficacy. We propose CodeClassPrompt, a text classification technique that harnesses prompt learning to extract rich knowledge associated with input sequences from pre-trained models, thereby eliminating the need for additional layers and lowering computational costs. By applying an attention mechanism, we synthesize multi-layered knowledge into task-specific features, enhancing classification accuracy. Our comprehensive experimentation across four distinct source code-related tasks reveals that CodeClassPrompt achieves competitive performance while significantly reducing computational overhead.

4.
Front Plant Sci ; 15: 1425100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055355

RESUMO

The high-throughput and full-time acquisition of images of crop growth processes, and the analysis of the morphological parameters of their features, is the foundation for achieving fast breeding technology, thereby accelerating the exploration of germplasm resources and variety selection by crop breeders. The evolution of embryonic soybean radicle characteristics during germination is an important indicator of soybean seed vitality, which directly affects the subsequent growth process and yield of soybeans. In order to address the time-consuming and labor-intensive manual measurement of embryonic radicle characteristics, as well as the issue of large errors, this paper utilizes continuous time-series crop growth vitality monitoring system to collect full-time sequence images of soybean germination. By introducing the attention mechanism SegNext_Attention, improving the Segment module, and adding the CAL module, a YOLOv8-segANDcal model for the segmentation and extraction of soybean embryonic radicle features and radicle length calculation was constructed. Compared to the YOLOv8-seg model, the model respectively improved the detection and segmentation of embryonic radicles by 2% and 1% in mAP50-95, and calculated the contour features and radicle length of the embryonic radicles, obtaining the morphological evolution of the embryonic radicle contour features over germination time. This model provides a rapid and accurate method for crop breeders and agronomists to select crop varieties.

5.
ACS Appl Bio Mater ; 7(5): 3316-3329, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38691017

RESUMO

Basic fibroblast growth factor (bFGF) plays an important role in active wound repair. However, the existing dosage forms in clinical applications are mainly sprays and freeze-dried powders, which are prone to inactivation and cannot achieve a controlled release. In this study, a bioactive wound dressing named bFGF-ATP-Zn/polycaprolactone (PCL) nanodressing with a "core-shell" structure was fabricated by emulsion electrospinning, enabling the sustained release of bFGF. Based on the coordination and electrostatic interactions among bFGF, ATP, and Zn2+, as well as their synergistic effect on promoting wound healing, a bFGF-ATP-Zn ternary combination system was prepared with higher cell proliferation activity and used as the water phase for emulsion electrospinning. The bFGF-ATP-Zn/PCL nanodressing demonstrated improved mechanical properties, sustained release of bFGF, cytocompatibility, and hemocompatibility. It increased the proliferation activity of human dermal fibroblasts (HDFs) and enhanced collagen secretion by 1.39 and 3.45 times, respectively, while reducing the hemolysis rate to 3.13%. The application of the bFGF-ATP-Zn/PCL nanodressing in mouse full-thickness skin defect repair showed its ability to accelerate wound healing and reduce wound scarring within 14 days. These results provide a research basis for the development and application of this bioactive wound dressing product.


Assuntos
Trifosfato de Adenosina , Materiais Biocompatíveis , Fator 2 de Crescimento de Fibroblastos , Cicatrização , Zinco , Animais , Humanos , Camundongos , Trifosfato de Adenosina/metabolismo , Bandagens , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Emulsões/química , Fator 2 de Crescimento de Fibroblastos/química , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fibroblastos/efeitos dos fármacos , Tamanho da Partícula , Poliésteres/química , Poliésteres/farmacologia , Cicatrização/efeitos dos fármacos , Zinco/química , Zinco/farmacologia
6.
Cell Commun Signal ; 22(1): 276, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755659

RESUMO

Traditionally, lactate has been considered a 'waste product' of cellular metabolism. Recent findings have shown that lactate is a substance that plays an indispensable role in various physiological cellular functions and contributes to energy metabolism and signal transduction during immune and inflammatory responses. The discovery of lactylation further revealed the role of lactate in regulating inflammatory processes. In this review, we comprehensively summarize the paradoxical characteristics of lactate metabolism in the inflammatory microenvironment and highlight the pivotal roles of lactate homeostasis, the lactate shuttle, and lactylation ('lactate clock') in acute and chronic inflammatory responses from a molecular perspective. We especially focused on lactate and lactate receptors with either proinflammatory or anti-inflammatory effects on complex molecular biological signalling pathways and investigated the dynamic changes in inflammatory immune cells in the lactate-related inflammatory microenvironment. Moreover, we reviewed progress on the use of lactate as a therapeutic target for regulating the inflammatory response, which may provide a new perspective for treating inflammation-related diseases.


Assuntos
Inflamação , Ácido Láctico , Humanos , Inflamação/metabolismo , Ácido Láctico/metabolismo , Animais , Doença Crônica , Transdução de Sinais , Doença Aguda
7.
Vaccine ; 42(22): 125992, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-38811268

RESUMO

Self-assembling virus-like particles (VLPs) are promising platforms for vaccine development. However, the unpredictability of the physical properties, such as self-assembly capability, hydrophobicity, and overall stability in engineered protein particles fused with antigens, presents substantial challenges in their downstream processing. We envision that these challenges can be addressed by combining more precise computer-aided molecular dynamics (MD) simulations with experimental studies on the modified products, with more to-date forcefield descriptions and larger models closely resembling real assemblies, realized by rapid advancement in computing technology. In this study, three chimeric designs based on the hepatitis B core (HBc) protein as model vaccine candidates were constructed to study and compare the influence of inserted epitopes as well as insertion strategy on HBc modifications. Large partial VLP models containing 17 chains for the HBc chimeric model vaccines were constructed based on the wild-type (wt) HBc assembly template. The findings from our simulation analysis have demonstrated good consistency with experimental results, pertaining to the surface hydrophobicity and overall stability of the chimeric vaccine candidates. Furthermore, the different impact of foreign antigen insertions on the HBc scaffold was investigated through simulations. It was found that separately inserting two epitopes into the HBc platform at the N-terminal and the major immunogenic regions (MIR) yields better results compared to a serial insertion at MIR in terms of protein structural stability. This study substantiates that an MD-guided design approach can facilitate vaccine development and improve its manufacturing efficiency by predicting products with extreme surface hydrophobicity or structural instability.


Assuntos
Antígenos do Núcleo do Vírus da Hepatite B , Simulação de Dinâmica Molecular , Nanopartículas , Vacinas de Partículas Semelhantes a Vírus , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos do Núcleo do Vírus da Hepatite B/química , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/química , Nanopartículas/química , Interações Hidrofóbicas e Hidrofílicas , Vacinas contra Hepatite B/imunologia , Vacinas contra Hepatite B/química , Epitopos/imunologia , Epitopos/química , Epitopos/genética , Humanos
8.
J Chromatogr A ; 1726: 464968, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38723492

RESUMO

The steric mass-action (SMA) model has been widely reported to describe the adsorption of proteins in different types of chromatographic adsorbents. Here in the present work, a pore-blocking steric mass-action model (PB-SMA) was developed for the adsorption of large-size bioparticles, which usually exhibit the unique pore-blocking characteristic on the adsorbent and thus lead to a fraction of ligands in the deep channels physically inaccessible to bioparticles adsorption, instead of being shielded due to steric hindrance by adsorbed bioparticles. This unique phenomenon was taken into account by introducing an additional parameter, Lin, which is defined as the inaccessible ligand densities in the physically blocked pore area, into the PB-SMA model. This fraction of ligand densities (Lin) will be deducted from the total ligand (Lt) for model development, thus the steric factor (σ) in the proposed PB-SMA will reflect the steric shielding effect on binding sites by adsorbed bioparticles more accurately than the conventional SMA model, which assumes that all ligands on the adsorbent have the same accessibility to the bioparticles. Based on a series of model assumptions, a PB-SMA model was firstly developed for inactivated foot-and-mouth disease virus (iFMDV) adsorption on immobilized metal affinity chromatography (IMAC) adsorbents. Model parameters for static adsorption including equilibrium constant (K), characteristic number of binding sites (n), and steric factor (σ) were determined. Compared with those derived from the conventional SMA model, the σ values derived from the PB-SMA model were dozens of times smaller and much closer to the theoretical maximum number of ligands shielded by a single adsorbed iFMDV, indicating the modified model was more accurate for bioparticles adsorption. The applicability of the PB-SMA model was further validated by the adsorption of hepatitis B surface antigen virus-like particles (HBsAg VLPs) on an ion exchange adsorbent with reasonably improved accuracy. Thus, it is considered that the PB-SMA model would be more accurate in describing the adsorption of bioparticles on different types of chromatographic adsorbents.


Assuntos
Cromatografia de Afinidade , Adsorção , Cromatografia de Afinidade/métodos , Vírus da Febre Aftosa/química , Ligantes , Porosidade , Modelos Químicos
9.
Macromol Rapid Commun ; 45(14): e2400105, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38623606

RESUMO

Intelligent materials derived from green and renewable bio-based materials garner widespread attention recently. Herein, shape memory polyurethane composite (PUTA/Fe) with fast response to near-infrared (NIR) light is successfully prepared by introducing Fe3+ into the tannic acid-based polyurethane (PUTA) matrix through coordination between Fe3+ and tannic acid. The results show that the excellent NIR light response ability is due to the even distribution of Fe3+ filler with good photo-thermal conversion ability. With the increase of Fe3+ content, the NIR light response shape recovery rate of PUTA/Fe composite films is significantly improved, and the shape recovery time is reduced from over 60 s to 40 s. In addition, the mechanical properties of PUTA/Fe composite film are also improved. Importantly, owing to the dynamic phenol-carbamate network within the polymer matrix, the PUTA/Fe composite film can reshape its permanent shape through topological rearrangement and show its good NIR light response shape memory performance. Therefore, PUTA/Fe composites with high content of bio-based material (TA content of 15.1-19.4%) demonstrate the shape memory characteristics of fast response to NIR light; so, it will have great potential in the application of new intelligent materials including efficient and environmentally friendly smart photothermal responder.


Assuntos
Carbamatos , Raios Infravermelhos , Ferro , Poliuretanos , Taninos , Taninos/química , Poliuretanos/química , Ferro/química , Carbamatos/química , Fenóis/química , Fenol/química , Materiais Inteligentes/química , Polifenóis
10.
Biomed Pharmacother ; 173: 116309, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479180

RESUMO

As the leading killer of life and health, stroke leads to limb paralysis, speech disorder, dysphagia, cognitive impairment, mental depression and other symptoms, which entail a significant financial burden to society and families. At present, physiology, clinical medicine, engineering, and materials science, advanced biomaterials standing on the foothold of these interdisciplinary disciplines provide new opportunities and possibilities for the cure of stroke. Among them, hydrogels have been endowed with more possibilities. It is well-known that hydrogels can be employed as potential biosensors, medication delivery vectors, and cell transporters or matrices in tissue engineering in tissue engineering, and outperform many traditional therapeutic drugs, surgery, and materials. Therefore, hydrogels become a popular scaffolding treatment option for stroke. Diverse synthetic hydrogels were designed according to different pathophysiological mechanisms from the recently reported literature will be thoroughly explored. The biological uses of several types of hydrogels will be highlighted, including pro-angiogenesis, pro-neurogenesis, anti-oxidation, anti-inflammation and anti-apoptosis. Finally, considerations and challenges of using hydrogels in the treatment of stroke are summarized.


Assuntos
Técnicas Biossensoriais , Acidente Vascular Cerebral , Humanos , Hidrogéis/uso terapêutico , Materiais Biocompatíveis , Engenharia Tecidual , Acidente Vascular Cerebral/tratamento farmacológico
11.
Sci Rep ; 14(1): 5095, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429374

RESUMO

The clinical application of conventional doxorubicin (CDOX) was constrained by its side effects. Liposomal doxorubicin was developed to mitigate these limitations, showing improved toxicity profiles. However, the adverse events associated with liposomal doxorubicin and CDOX have not yet been comprehensively evaluated in clinical settings. The FAERS data from January 2004 to December 2022 were collected to analyze the adverse events of liposomal doxorubicin and CDOX. Disproportionate analysis and Bayesian analysis were employed to quantify this association. Our analysis incorporated 68,803 adverse event reports related to Doxil/Caelyx, Myocet and CDOX. The relative odds ratios (RORs, 95%CI) for febrile neutropenia associated with CDOX, Doxil/Caelyx, and Myocet were 42.45 (41.44; 43.48), 17.53 (16.02; 19.20), and 34.68 (26.63; 45.15) respectively. For cardiotoxicity, they were 38.87(36.41;41.49), 17.96 (14.10; 22.86), and 37.36 (19.34; 72.17). For Palmar-Plantar Erythrodysesthesia (PPE), the RORs were 6.16 (5.69; 6.68), 36.13 (32.60; 40.06), and 19.69 (11.59; 33.44). Regarding onset time, significant differences adverse events including neutropenia, PPE, pneumonia and malignant neoplasm progression. This study indicates that clinical monitoring for symptoms of cardiotoxicity of CDOX and Myocet, and PPE and interstitial lung disease of Doxil should be performed. Additionally, the onset time of febrile neutropenia, malignant neoplasm progression, and pneumonia associated with Doxil and Myocet merits particular attention. Continuous surveillance, risk evaluations, and additional comparative studies between liposomal doxorubicin and CDOX were recommended.


Assuntos
Doxorrubicina/análogos & derivados , Neoplasias , Neutropenia , Pneumonia , Humanos , Cardiotoxicidade/tratamento farmacológico , Teorema de Bayes , Doxorrubicina/efeitos adversos , Lipossomos , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Pneumonia/tratamento farmacológico , Polietilenoglicóis
12.
Int J Biol Macromol ; 261(Pt 2): 129838, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307428

RESUMO

A novel α-amylase Amy03713 was screened and cloned from the starch utilization strain Vibrio alginolyticus LHF01. When heterologously expressed in Escherichia coli, Amy03713 exhibited the highest enzyme activity at 45 °C and pH 7, maintained >50 % of the enzyme activity in the range of 25-75 °C and pH 5-9, and sustained >80 % of the enzyme activity in 25 % (w/v) of NaCl solution, thus showing a wide range of adapted temperatures, pH, and salt concentrations. Halomonas bluephagenesis harboring amy03713 gene was able to directly utilize starch. With optimized amylase expression, H. bluephagenesis could produce poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB). When cultured for PHB production, recombinant H. bluephagenesis was able to grow up to a cell dry weight of 11.26 g/L, achieving a PHB titer of 6.32 g/L, which is the highest titer that has been reported for PHB production from starch in shake flasks. This study suggests that Amy03713 is an ideal amylase for PHA production using starch as the carbon source in H. bluephagenesis.


Assuntos
Halomonas , Ácidos Pentanoicos , Poli-Hidroxialcanoatos , Halomonas/genética , Halomonas/metabolismo , Carbono/metabolismo , Amido/metabolismo , Hidroxibutiratos/metabolismo , alfa-Amilases/genética , alfa-Amilases/metabolismo , Poliésteres/metabolismo
13.
J Control Release ; 368: 275-289, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382812

RESUMO

Virus like particles (VLPs) have been well recognized as one of the most important vaccine platforms due to their structural similarity to natural viruses to induce effective humoral and cellular immune responses. Nevertheless, lack of viral nucleic acids in VLPs usually leads the vaccine candidates less efficient in provoking innate immune against viral infection. Here, we constructed a biomimetic dual antigen hybrid influenza nanovaccines THM-HA@Mn with robust immunogenicity via in situ synthesizing a stimulator of interferon genes (STING) agonist Mn3O4 inside the cavity of a recombinant Hepatitis B core antigen VLP (HBc VLP) having fused SpyTag and influenza M2e antigen peptides (Tag-HBc-M2e, THM for short), followed by conjugating a recombinant hemagglutinin (rHA) antigen on the surface of the nanoparticles through SpyTag/SpyCatcher ligating. Such inside Mn3O4 immunostimulator-outside rHA antigen design, together with the chimeric M2e antigen on the HBc skeleton, enabled the synthesized hybrid nanovaccines THM-HA@Mn to well imitate the spatial distribution of M2e/HA antigens and immunostimulant in natural influenza virus. In vitro cellular experiments indicated that compared with the THM-HA antigen without Mn3O4 and a mixture vaccine consisting of THM-HA + MnOx, the THM-HA@Mn hybrid nanovaccines showed the highest efficacies in dendritic cells uptake and in promoting BMDC maturation, as well as inducing expression of TNF-α and type I interferon IFN-ß. The THM-HA@Mn also displayed the most sustained antigen release at the injection site, the highest efficacies in promoting the DC maturation in lymph nodes and germinal center B cells activation in the spleen of the immunized mice. The co-delivery of immunostimulant and antigens enabled the THM-HA@Mn nanovaccines to induce the highest systemic antigen-specific antibody responses and cellular immunogenicity in mice. Together with the excellent colloid dispersion stability, low cytotoxicity, as well as good biosafety, the synthetic hybrid nanovaccines presented in this study offers a promising strategy to design VLP-based vaccine with robust natural and adaptive immunogenicity against emerging viral pathogens.


Assuntos
Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Vacinas de Partículas Semelhantes a Vírus , Animais , Camundongos , Humanos , Influenza Humana/prevenção & controle , Vacinas de Partículas Semelhantes a Vírus/genética , Imunidade Celular , Adjuvantes Imunológicos , Camundongos Endogâmicos BALB C , Anticorpos Antivirais , Infecções por Orthomyxoviridae/prevenção & controle
14.
Biotechnol Bioeng ; 121(1): 206-218, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37747706

RESUMO

The messenger RNA (mRNA) 5'-cap structure is indispensable for mRNA translation initiation and stability. Despite its importance, large-scale production of capped mRNA through in vitro transcription (IVT) synthesis using vaccinia capping enzyme (VCE) is challenging, due to the requirement of tedious and multiple pre-and-post separation steps causing mRNA loss and degradation. Here in the present study, we found that the VCE together with 2'-O-methyltransferase can efficiently catalyze the capping of poly dT media-tethered mRNA to produce mRNA with cap-1 structure under an optimized condition. We have therefore designed an integrated purification and solid-based capping protocol, which involved capturing the mRNA from the IVT system by using poly dT media through its affinity binding for 3'-end poly-A in mRNA, in situ capping of mRNA 5'-end by supplying the enzymes, and subsequent eluting of the capped mRNA from the poly dT media. Using mRNA encoding the enhanced green fluorescent protein as a model system, we have demonstrated that the new strategy greatly simplified the mRNA manufacturing process and improved its overall recovery without sacrificing the capping efficiency, as compared with the conventional process, which involved at least mRNA preseparation from IVT, solution-based capping, and post-separation and recovering steps. Specifically, the new process accomplished a 1.76-fold (84.21% over 47.79%) increase in mRNA overall recovery, a twofold decrease in operation time (70 vs. 140 min), and similar high capping efficiency (both close to 100%). Furthermore, the solid-based capping process greatly improved mRNA stability, such that the integrity of the mRNA could be well kept during the capping process even in the presence of exogenously added RNase; in contrast, mRNA in the solution-based capping process degraded almost completely. Meanwhile, we showed that such a strategy can be operated both in a batch mode and in an on-column continuous mode. The results presented in this work demonstrated that the new on-column capping process developed here can accomplish high capping efficiency, enhanced mRNA recovery, and improved stability against RNase; therefore, can act as a simple, efficient, and cost-effective platform technology suitable for large-scale production of capped mRNA.


Assuntos
Poli T , Ribonucleases , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Capuzes de RNA/química , Capuzes de RNA/genética
15.
Biotechnol Adv ; 70: 108302, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38101552

RESUMO

Halophiles are salt-loving microorganisms known to have their natural resistance against media contamination even when cultivated in nonsterile and continuous bioprocess system, thus acting as promising cell factories for Next Generation of Industrial Biotechnology (NGIB). NGIB - a successor to the traditional industrial biotechnology, is a more sustainable and efficient bioprocess technology while saving energy and water in a more convenient way as well as reducing the investment cost and skilled workforce requirement. Numerous studies have achieved intriguing outcomes during synthesis of different metabolite using halophiles such as polyhydroxyalkanoates (PHA), ectoine, biosurfactants, and carotenoids. Present-day development in genetic maneuverings have shown optimistic effects on the industrial applications of halophiles. However, viable and competent genetic manipulation system and gene editing tools are critical to accelerate the process of halophile engineering. With the aid of such powerful gene manipulation systems, exclusive microbial chassis are being crafted with desirable features to breed another innovative area of research such as synthetic biology. This review provides an aerial perspective on how the expansion of adaptable gene manipulation toolkits in halophiles are contributing towards biotechnological advancement, and also focusses on their subsequent application for production improvement. This current methodical and comprehensive review will definitely help the scientific fraternity to bridge the gap between challenges and opportunities in halophile engineering.


Assuntos
Biotecnologia , Poli-Hidroxialcanoatos , Edição de Genes , Poli-Hidroxialcanoatos/genética , Poli-Hidroxialcanoatos/metabolismo , Biologia Sintética , Carotenoides , Engenharia Metabólica
16.
Lab Invest ; 104(2): 100306, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38104864

RESUMO

Immunocheckpoint inhibitors have shown impressive efficacy in patients with colon cancer and other types of solid tumor that are mismatch repair-deficient (dMMR). Currently, PCR-capillary electrophoresis is one of the mainstream detection methods for dMMR, but its accuracy is still limited by germline mismatch repair (MMR) mutations, the functional redundancy of the MMR system, and abnormal methylation of MutL Homolog 1 promoter. Therefore, this study aimed to develop new biomarkers for dMMR based on artificial intelligence (AI) and pathologic images, which may help to improve the detection accuracy. To screen for the differential expression genes (DEGs) in dMMR patients and validate their diagnostic and prognostic efficiency, we used the expression profile data from the Cancer Genome Atlas (TCGA). The results showed that the expression of Immunoglobulin Lambda Joining 3 in dMMR patients was significantly downregulated and negatively correlated with the prognosis. Meanwhile, our diagnostic models based on pathologic image features showed good performance with area under the curves (AUCs) of 0.73, 0.86, and 0.81 in the training, test, and external validation sets (Jiangsu Traditional Chinese Medicine Hospital cohort). Based on gene expression and pathologic characteristics, we developed an effective prognosis model for dMMR patients through multiple Cox regression analysis (with AUC values of 0.88, 0.89, and 0.88 at 1-, 3-, and 5-year intervals, respectively). In conclusion, our results showed that Immunoglobulin Lambda Joining 3 and nucleus shape-related parameters (such as nuclear texture, nuclear eccentricity, nuclear size, and nuclear pixel intensity) were independent diagnostic and prognostic factors, suggesting that they could be used as new biomarkers for dMMR patients.


Assuntos
Adenocarcinoma , Neoplasias Encefálicas , Neoplasias do Colo , Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Humanos , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Reparo de Erro de Pareamento de DNA/genética , Inteligência Artificial , Multiômica , Neoplasias Colorretais/patologia , Biomarcadores , Imunoglobulinas/genética
17.
J Biomol Struct Dyn ; : 1-14, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37908124

RESUMO

Self-assembling protein nanoparticles showed promise for vaccine design due to efficient antigen presentations and safety. However, the unpredictable formations of epitopes-fused protein assemblies remain challenging in the upstream design. This study suggests employing molecular dynamic (MD) simulations to investigate the assembly properties of Hepatitis B core protein (HBc) from thermodynamic perspectives. Eight HBc derivatives were expressed in E. coli, with their self-assembly properties characterised by high-performance liquid chromatography and transmission electron microscopy. MD simulations on the dimers, based on AlphaFold-predicted 3D structures, analysed the derivative at the atomic level. Results revealed that HBc derivatives can form dissociative polymers or large multi-subunit structures due to assembly failures. The instability of the dimer in aqueous solvents or inappropriate intradimer distances could cause major assembly failures. Polar solvation energies played a vital role too in forming assemble-incompetent dimers. Importantly, our study demonstrated that MD simulations on dimers can provide preliminary predictions on the assembly properties of HBc derivatives, thus aiding vaccine design by lowering the risk of self-assembling failures in engineered proteins.Communicated by Ramaswamy H. Sarma.

18.
Front Oncol ; 13: 1278563, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37886171

RESUMO

Background: The localization of pulmonary nodules prior to thoracoscopic surgery remains challenging for thoracic surgeons, especially for those nodules that are not visible or palpable on the lung surface. Our study is a simple and effective minimally invasive method using indocyanine green through a special pathway to locate pulmonary nodules and fluorescence thoracoscopic surgery. Methods: Thoracoscopic surgery was performed for 18 undiagnosed peripheral non-solid nodules no larger than 2 cm after location. After 0.3 mg/kg indocyanine green was injected through the peripheral vein, the puncture needle was pulled out after it reached approximately 1 cm of the pulmonary parenchyma near the nodules. This was followed by transfer to the operating room. The nodule was initially localized by using a near-infrared thoracoscope to visualize indocyanine green fluorescence. Then, thoracoscopic resection was performed. Results: Eighteen patients received this special and simple localization method, and underwent near-infrared, image-guided, video-assisted thoracoscopic surgery resection. Median computed tomography (CT) tumor size was 1.2 cm. Median depth from the pleural surface is 1.6 cm (range, 0.1-4.6 cm). The median time of CT-guided intervention was 12 min. The duration of thoracoscopic surgery was 67 min. Indocyanine green fluorescence was clearly identified in 17 of 18 patients (94.4%). The surgical margins were all negative on final pathology. The final diagnoses included 17 primary lung cancers, and 1 benign lung tumor. Conclusions: CT-guided single puncture of indocyanine green after peripheral intravenous injection is a simple, effective, and safe method to locate the nodule. This offers surgeons the ease of localization through direct indocyanine green fluorescence imaging, and it can be used as an effective alternative to other placement methods of locating pulmonary nodules.

19.
Sheng Wu Gong Cheng Xue Bao ; 39(10): 4295-4307, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37877406

RESUMO

We developed a method for accurate quantification of the intact virus particles in inactivated avian influenza virus feedstocks. To address the problem of impurities interference in the detection of inactivated avian influenza virus feedstocks by direct high performance size exclusion chromatography (HPSEC), we firstly investigated polyethylene glycol (PEG) precipitation and ion exchange chromatography (IEC) for H5N8 antigen purification. Under the optimized conditions, the removal rate of impurity was 86.87% in IEC using DEAE FF, and the viral hemagglutination recovery was 100%. HPSEC was used to analyze the pretreated samples. The peak of 8.5-10.0 min, which was the characteristic adsorption of intact virus, was analyzed by SDS-PAGE and dynamic light scattering. It was almost free of impurities and the particle size was uniform with an average particle size of 127.7 nm. After adding antibody to the IEC pretreated samples for HPSEC detection, the characteristic peak disappeared, indicating that IEC pretreatment effectively removed the impurities. By coupling HPSEC with multi-angle laser scattering technique (MALLS), the amount of intact virus particles in the sample could be accurately quantified with a good linear relationship between the number of virus particles and the chromatographic peak area (R2=0.997). The established IEC pretreatment-HPSEC-MALLS assay was applied to accurate detection of the number of intact virus particles in viral feedstocks of different subtypes (H7N9), different batches and different concentrations, all with good applicability and reproducibility, Relative standard deviation < 5%, n=3.


Assuntos
Subtipo H7N9 do Vírus da Influenza A , Influenza Aviária , Animais , Reprodutibilidade dos Testes , Cromatografia em Gel , Vírion , Lasers
20.
Expert Opin Drug Saf ; : 1-8, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37622438

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) therapy combined with anti-vascular endothelial growth factor (anti-VEGF) regimens showed new hope for cancer patients and considered as future pillar of cancer therapy. However, severe cutaneous adverse reactions (SCARs) in patients with ICIs and anti-VEGF combined therapy raise a serious concern and remain thoroughly assessed in clinics. RESEARCH DESIGN AND METHODS: Data retrieved from the first quarter of 2004 to the third quarter of 2022 in FAERS database underwent disproportionality analysis and Bayesian analysis were utilized to detect and assess the SCAR signals of ICIs and ICIs and anti-VEGF combined therapy for comparison. RESULTS: In total, 854 (1.10%) and 80 (1.06%) reports on SCARs associated with ICIs and a combination of ICIs and anti-VEGF therapy, respectively, were analyzed. Most of SCARs reports were associated with the use of pembrolizumab (36.01%), nivolumab (23.97%) and a combination of ipilimumab and nivolumab (19.71%). A use of atezolizumab and bevacizumab combined therapy (60.00%) caused the most SCARs records out of ICIs and anti-VEGF combined therapies. CONCLUSIONS: Treatment with joint therapy of ICIs and anti-VEGF agents may cause severe cutaneous adverse events. It is vital to identify ICI-related SCARs early, and to manage them appropriately.

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