-
Npj Viruses 2024The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an epidemic, zoonotically emerging pathogen initially reported in Saudi Arabia in 2012. MERS-CoV has the...
The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an epidemic, zoonotically emerging pathogen initially reported in Saudi Arabia in 2012. MERS-CoV has the potential to mutate or recombine with other coronaviruses, thus acquiring the ability to efficiently spread among humans and become pandemic. Its high mortality rate of up to 35% and the absence of effective targeted therapies call for the development of antiviral drugs for this pathogen. Since the beginning of the SARS-CoV-2 pandemic, extensive research has focused on identifying protease inhibitors for the treatment of SARS-CoV-2. Our intention was therefore to assess whether these protease inhibitors are viable options for combating MERS-CoV. To that end, we used previously established protease assays to quantify inhibition of SARS-CoV-2, MERS-CoV and other main proteases. Nirmatrelvir inhibited several of these proteases, whereas ensitrelvir was less broadly active. To simulate nirmatrelvir's clinical use against MERS-CoV and subsequent resistance development, we applied a safe, surrogate virus-based system. Using the surrogate virus, we previously selected hallmark mutations of SARS-CoV-2-M, such as T21I, M49L, S144A, E166A/K/V and L167F. In the current study, we selected a pool of MERS-CoV-M mutants, characterized the resistance and modelled the steric effect of catalytic site mutants S142G, S142R, S147Y and A171S.
PubMed: 38933182
DOI: 10.1038/s44298-024-00028-2 -
Frontiers in Medicine 2024Intestinal ischemia/reperfusion is a prevalent pathological process that can result in intestinal dysfunction, bacterial translocation, energy metabolism disturbances,... (Review)
Review
Intestinal ischemia/reperfusion is a prevalent pathological process that can result in intestinal dysfunction, bacterial translocation, energy metabolism disturbances, and subsequent harm to distal tissues and organs via the circulatory system. Acute lung injury frequently arises as a complication of intestinal ischemia/reperfusion, exhibiting early onset and a grim prognosis. Without appropriate preventative measures and efficacious interventions, this condition may progress to acute respiratory distress syndrome and elevate mortality rates. Nonetheless, the precise mechanisms and efficacious treatments remain elusive. This paper synthesizes recent research models and pertinent injury evaluation criteria within the realm of acute lung injury induced by intestinal ischemia/reperfusion. The objective is to investigate the roles of pathophysiological mechanisms like oxidative stress, inflammatory response, apoptosis, ferroptosis, and pyroptosis; and to assess the strengths and limitations of current therapeutic approaches for acute lung injury stemming from intestinal ischemia/reperfusion. The goal is to elucidate potential targets for enhancing recovery rates, identify suitable treatment modalities, and offer insights for translating fundamental research into clinical applications.
PubMed: 38933104
DOI: 10.3389/fmed.2024.1399744 -
[Pulmonary PET /CT image instance segmentation based on dense interactive feature fusion Mask RCNN].Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Jun 2024There are some problems in positron emission tomography/ computed tomography (PET/CT) lung images, such as little information of feature pixels in lesion regions,...
There are some problems in positron emission tomography/ computed tomography (PET/CT) lung images, such as little information of feature pixels in lesion regions, complex and diverse shapes, and blurred boundaries between lesions and surrounding tissues, which lead to inadequate extraction of tumor lesion features by the model. To solve the above problems, this paper proposes a dense interactive feature fusion Mask RCNN (DIF-Mask RCNN) model. Firstly, a feature extraction network with cross-scale backbone and auxiliary structures was designed to extract the features of lesions at different scales. Then, a dense interactive feature enhancement network was designed to enhance the lesion detail information in the deep feature map by interactively fusing the shallowest lesion features with neighboring features and current features in the form of dense connections. Finally, a dense interactive feature fusion feature pyramid network (FPN) network was constructed, and the shallow information was added to the deep features one by one in the bottom-up path with dense connections to further enhance the model's perception of weak features in the lesion region. The ablation and comparison experiments were conducted on the clinical PET/CT lung image dataset. The results showed that the APdet, APseg, APdet_s and APseg_s indexes of the proposed model were 67.16%, 68.12%, 34.97% and 37.68%, respectively. Compared with Mask RCNN (ResNet50), APdet and APseg indexes increased by 7.11% and 5.14%, respectively. DIF-Mask RCNN model can effectively detect and segment tumor lesions. It provides important reference value and evaluation basis for computer-aided diagnosis of lung cancer.
Topics: Humans; Lung Neoplasms; Positron Emission Tomography Computed Tomography; Lung; Algorithms; Image Processing, Computer-Assisted; Neural Networks, Computer
PubMed: 38932539
DOI: 10.7507/1001-5515.202309026 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Jun 2024This paper investigates the variation of lung tissue dielectric properties with tidal volume under conditions to provide reliable and valid a priori information for...
This paper investigates the variation of lung tissue dielectric properties with tidal volume under conditions to provide reliable and valid a priori information for techniques such as microwave imaging. In this study, the dielectric properties of the lung tissue of 30 rabbits were measured using the open-end coaxial probe method in the frequency band of 100 MHz to 1 GHz, and 6 different sets of tidal volumes (30, 40, 50, 60, 70, 80 mL) were set up to study the trends of the dielectric properties, and the data at 2 specific frequency points (433 and 915 MHz) were analyzed statistically. It was found that the dielectric coefficient and conductivity of lung tissue tended to decrease with increasing tidal volume in the frequency range of 100 MHz to 1 GHz, and the differences in the dielectric properties of lung tissue for the 6 groups of tidal volumes at 2 specific frequency points were statistically significant. This paper showed that the dielectric properties of lung tissue tend to vary non-linearly with increasing tidal volume. Based on this, more accurate biological tissue parameters can be provided for bioelectromagnetic imaging techniques such as microwave imaging, which could provide a scientific basis and experimental data support for the improvement of diagnostic methods and equipment for lung diseases.
Topics: Animals; Rabbits; Tidal Volume; Lung; Electric Impedance; Electric Conductivity; Microwave Imaging; Microwaves
PubMed: 38932529
DOI: 10.7507/1001-5515.202312044 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Jun 2024Electrical impedance tomography (EIT) is a non-radiation, non-invasive visual diagnostic technique. In order to improve the imaging resolution and the removing artifacts...
Electrical impedance tomography (EIT) is a non-radiation, non-invasive visual diagnostic technique. In order to improve the imaging resolution and the removing artifacts capability of the reconstruction algorithms for electrical impedance imaging in human-chest models, the HMANN algorithm was proposed using the Hadamard product to optimize multilayer artificial neural networks (MANN). The reconstructed images of the HMANN algorithm were compared with those of the generalized vector sampled pattern matching (GVSPM) algorithm, truncated singular value decomposition (TSVD) algorithm, backpropagation (BP) neural network algorithm, and traditional MANN algorithm. The simulation results showed that the correlation coefficient of the reconstructed images obtained by the HMANN algorithm was increased by 17.30% in the circular cross-section models compared with the MANN algorithm. It was increased by 13.98% in the lung cross-section models. In the lung cross-section models, some of the correlation coefficients obtained by the HMANN algorithm would decrease. Nevertheless, the HMANN algorithm retained the image information of the MANN algorithm in all models, and the HMANN algorithm had fewer artifacts in the reconstructed images. The distinguishability between the objects and the background was better compared with the traditional MANN algorithm. The algorithm could improve the correlation coefficient of the reconstructed images, and effectively remove the artifacts, which provides a new direction to effectively improve the quality of the reconstructed images for EIT.
Topics: Humans; Neural Networks, Computer; Electric Impedance; Algorithms; Tomography; Thorax; Image Processing, Computer-Assisted; Lung
PubMed: 38932528
DOI: 10.7507/1001-5515.202305047 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Jun 2024Monitoring airway impedance has significant clinical value in accurately assessing and diagnosing pulmonary function diseases at an early stage. To address the issue of...
Monitoring airway impedance has significant clinical value in accurately assessing and diagnosing pulmonary function diseases at an early stage. To address the issue of large oscillator size and high power consumption in current pulmonary function devices, this study adopts a new strategy of expiration-driven oscillation. A lightweight and low-power airway impedance monitoring system with integrated sensing, control circuitry, and dynamic feedback system, providing visual feedback on the system's status, was developed. The respiratory impedance measurement experiments and statistical comparisons indicated that the system could achieve stable measurement of airway impedance at 5 Hz. The frequency spectrum curves of respiratory impedance ( and ) showed consistent trends with those obtained from the clinical pulmonary function instrument, specifically the impulse oscillometry system (IOS). The differences between them were all less than 1.1 cm H O·s/L. Additionally, there was a significant statistical difference in the respiratory impedance 5 between the exercise and rest groups, which suggests that the system can measure the variability of airway resistance parameters during exercise. Therefore, the impedance monitoring system developed in this study supports subjects in performing handheld, continuous measurements of dynamic changes in airway impedance over an extended period of time. This research provides a foundation for further developing low-power, portable, and even wearable devices for dynamic monitoring of pulmonary function.
Topics: Humans; Electric Impedance; Airway Resistance; Oscillometry; Monitoring, Physiologic; Respiratory Function Tests; Exhalation; Equipment Design; Exercise
PubMed: 38932527
DOI: 10.7507/1001-5515.202309058 -
Cancer Science Jun 2024Atypical L858R or other L858X mutations in the epidermal growth factor receptor (EGFR) gene, beyond the classical EGFR mutation caused by c.2573 T > G, have been...
Outcomes in non-small cell lung cancer with uncommon epidermal growth factor receptor L858 substitutions under first-line epidermal growth factor receptor tyrosine kinase inhibitors: A large real-world cohort study.
Atypical L858R or other L858X mutations in the epidermal growth factor receptor (EGFR) gene, beyond the classical EGFR mutation caused by c.2573 T > G, have been identified in non-small cell lung cancer (NSCLC), yet their genomic features and survival benefits with EGFR tyrosine kinase inhibitor (TKI) treatment have not been fully explored. We retrospectively enrolled 489 NSCLC patients with baseline tumor tissue/plasma samples carrying uncommon EGFR (N = 124), EGFR (N = 17), or classical EGFR mutations (N = 348). The comparison of molecular features was performed using treatment-naïve tumor tissues. Survival benefits and resistance mechanisms of first-line EGFR TKI treatment were studied in an advanced disease subcohort. NSCLCs harboring uncommon EGFR had lower TP53 mutation prevalence (p = 0.04) and chromosome instability scores (p = 0.02) than those with classical EGFR. Concomitant EGFR mutations were enriched in NSCLCs with EGFR (p < 0.01), with cooccurrence in those carrying EGFR. Patients with uncommon EGFR experienced improved progression-free survival (PFS) compared to those with classical EGFR (median: 13.0 vs. 10.0 months, hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.41-0.80). The association remained significant when adjusting for sex, age, histological subtype, TKI category, and anti-vascular therapy (HR: 0.55, 95% CI: 0.39-0.77). Furthermore, EGFR patients showed enhanced first-line PFS (vs. classical EGFR, HR: 0.26, 95% CI: 0.10-0.67), potentially benefiting more from afatinib. Additionally, NSCLCs with uncommon EGFR and classical EGFR had similar resistance profiles to EGFR TKIs. In conclusion, NSCLCs carrying atypical EGFR L858 aberrations, which had fewer TP53 mutations and higher chromosome stability, exhibited improved PFS under first-line EGFR TKIs than those with the classical EGFR.
PubMed: 38932450
DOI: 10.1111/cas.16250 -
Vaccines Jun 2024Influenza viruses can cause highly infectious respiratory diseases, posing noteworthy epidemic and pandemic threats. Vaccination is the most cost-effective intervention...
Influenza viruses can cause highly infectious respiratory diseases, posing noteworthy epidemic and pandemic threats. Vaccination is the most cost-effective intervention to prevent influenza and its complications. However, reliance on embryonic chicken eggs for commercial influenza vaccine production presents potential risks, including reductions in efficacy due to HA gene mutations and supply delays due to scalability challenges. Thus, alternative platforms are needed urgently to replace egg-based methods and efficiently meet the increasing demand for vaccines. In this study, we employed a baculovirus expression vector system to engineer HA, NA, and M1 genes from seasonal influenza strains A/H1N1, A/H3N2, B/Yamagata, and B/Victoria, generating virus-like particle (VLP) vaccine antigens, H1N1-VLP, H3N2-VLP, Yamagata-VLP, and Victoria-VLP. We then assessed their functional and antigenic characteristics, including hemagglutination assay, protein composition, morphology, stability, and immunogenicity. We found that recombinant VLPs displayed functional activity, resembling influenza virions in morphology and size while maintaining structural integrity. Comparative immunogenicity assessments in mice showed that our quadrivalent VLPs were consistent in inducing hemagglutination inhibition and neutralizing antibody titers against homologous viruses compared to both commercial recombinant HA and egg-based vaccines (Vaxigrip). The findings highlight insect cell-based VLP vaccines as promising candidates for quadrivalent seasonal influenza vaccines. Further studies are worth conducting.
PubMed: 38932396
DOI: 10.3390/vaccines12060667 -
Vaccines Jun 2024This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus...
This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus (SwIAV). The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose-chitosan nanoparticles (mChit-NPs). Optimization of mChit-NPs included evaluating size, zeta potential, and cytotoxicity, with a 1:9 mass ratio of antigen to NP demonstrating high loading efficacy and non-cytotoxic properties suitable for intranasal vaccination. In a heterologous H1N1 pig challenge trial, the mChit-NP intranasal vaccine induced cross-reactive sIgA antibodies in the respiratory tract, surpassing those of a commercial SwIAV vaccine. The encapsulated mChit-NP vaccine induced high virus-specific neutralizing antibody and robust cellular immune responses, while the adsorbed vaccine elicited specific high IgG and hemagglutinin inhibition antibodies. Importantly, both the mChit-NP vaccines reduced challenge heterologous viral replication in the nasal cavity higher than commercial swine influenza vaccine. In summary, a novel intranasal mChit-NP vaccine platform activated both the arms of the immune system and is a significant advancement in swine influenza vaccine design, demonstrating its potential effectiveness for pig immunization.
PubMed: 38932376
DOI: 10.3390/vaccines12060647 -
Vaccines Jun 2024Community infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have increased rapidly since the emergence of the Omicron strain. During the eighth...
BACKGROUND
Community infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have increased rapidly since the emergence of the Omicron strain. During the eighth and ninth pandemic waves-when movement restrictions in the community were eased-the all-case registration system was changed, and the actual status of infection became uncertain.
METHODS
We conducted regular rapid antigen tests (R-RATs) once or twice a week as self-testing to examine the actual state of coronavirus disease (COVID-19) diagnosis among healthcare employees.
RESULTS
Overall, 320 (1.42/day) and 299 (1.76/day) employees were infected in the eighth and ninth pandemic waves. During both periods, 59/263 doctors (22.4%), 335/806 nurses (41.6%), 92/194 administrative employees (47.4%), and 129/218 clinical laboratory technicians (59.2%) were infected. In the eighth wave, 56 of 195 employees were infected through close contact; in the ninth wave, 26 of 62 employees were infected. No significant difference was observed in the number of vaccinations between infected and non-infected employees. The positivity rate of R-RATs was 0.41% and 0.45% in the eighth and ninth waves. R-RATs detected infection in 212 and 229 employees during the eighth and ninth waves, respectively; the ratio of R-RAT-detected positive employees to those who reported infection was significantly higher during the ninth wave (odds ratio: 1.67, 95% confidence interval: 1.17-2.37, < 0.001).
CONCLUSIONS
The number of infected healthcare employees remained high during the eighth and ninth pandemic waves in Japan. The R-RAT is considered effective for detecting mild or asymptomatic COVID-19 at an early stage and at a high rate in healthcare employees.
PubMed: 38932374
DOI: 10.3390/vaccines12060645