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In this work, the phase separation behavior and pattern formation in binary fluids with chemical reactions controlled by ultrasonic radiation were systematically investigated. We incorporated the density-dependent Arrhenius equation into a novel and modified model for phase separation. The coupling effects of the pre-exponential factor K, density, and frequency on the phase separation under the condition of ultrasonic field-regulated chemical reactions were evaluated. 1) The rate of chemical reaction can be slowed down and even blocked by controlling the frequency of the ultrasonic field. 2)We have established a criterion for evaluating the competition between chemical reactions and the ultrasonic fields. When the value of pre-exponential factor K is greater than or equal to 10 −4 , phase separation is primarily regulated by the chemical reaction; otherwise, the ultrasonic field dominates the phase separation. 3) By analyzing the average structure factor, it was quantitatively proven that an increase in the frequency can significantly shorten the phase preservation period of the chemical reaction and ultrasonic radiation force and accelerate the merging of the separated phases into a larger phase. 4) We have successfully simulated the morphological evolution of phase separation regulated by traveling waves in the ultrasonic field.

In this paper, a three dimensional discrete eco-epidemiological model with Holling type-III functional response is proposed. Boundedness of the solutions of the system is analyzed. Existence condition and stability of all fixed points are discussed for the proposed model. Furthermore, we obtained the transcritical bifurcation surfaces of the system by bifurcation theory. Based on the explicit criteria for the Neimark Sacker bifurcation and flip bifurcation, we obtained that the system undergoes these two types of bifurcations at the positive fixed point. Then we apply a hybrid control strategy that based on both parameter perturbation and a state feedback strategy to control the Neimark-Sacker bifurcation. Finally, some numerical simulations are carried out to support the analytical results.

Angiogenesis is a critical, fine-tuned, multi-staged biological process. Tip-stalk cell selection and shuffling are the building blocks of sprouting angiogenesis. Accumulated evidences show that tip-stalk cell selection and shuffling are regulated by a variety of physical, chemical and biological factors, especially the interaction among multiple genes, their products and environments. The classic Notch-VEGFR, Slit-Robo, ECM-binding integrin, semaphorin and CCN family play important roles in tip-stalk cell selection and shuffling. In this review, we outline the progress and prospect in the mechanism and the roles of the various molecules and related signaling pathways in endothelial tip-stalk cell selection and shuffling. In the future, the regulators of tip-stalk cell selection and shuffling would be the potential markers and targets for angiogenesis.

Given the insufficient understanding of the bearing mechanism and failure modes of large-diameter under-reamed piles in complex strata, this study conducted scaled laboratory model tests based on similarity theory. A visualized “semi-model pile static loading-reaction frame” system was established to systematically investigate the influence of under-reaming angle (0° ~ 25°) and pile embedment depth (60 ~ 80 cm) on the bearing characteristics and failure mechanisms of the pile foundation. The results show that: 1) The under-reaming angle is the dominant factor controlling bearing performance. A reasonable increase in this angle can significantly enhance the ultimate bearing capacity, with a 204.99% improvement observed at 20° compared to the uniform-section pile. However, the enhancement effect weakens with increasing embedment depth. Comprehensive analysis suggests that 15° ~ 20° is the optimal under-reaming angle range; an excessive angle induces stress concentration at the “shoulder” of the pile, leading to interfacial detachment between pile and soil, thus limiting further improvement in bearing capacity. 2) The under-reamed structure effectively optimizes the load transfer path along the pile shaft. The end bearing resistance ratio increases first and then decreases with the under-reaming angle, reaching a maximum of 65.09% at 20°, indicating a transition of the load transfer mechanism from shaft-resistance-dominated to end-resistance-dominated behavior. 3) The failure morphology of the pile toe rock evolves from “penetrative shear failure” in the uniform pile (failure zone ≈ 1.25D) to “fan-shaped compaction” at the optimal under-reaming angle (≈ 4D), and further enlarging the angle results in unstable “bulging and collapse” failure. This study systematically reveals the full-process mechanism from load bearing to failure in large-diameter under-reamed piles, providing a theoretical basis for optimizing design parameters and predicting failure behavior. The findings offer valuable references for engineering design and improvement of design codes.

Temozolomide (TMZ) was used for the treatment of glioblastoma (GBM) for over a decade, but its treatment benefits are limited by acquired resistance, a process that remains incompletely understood. Here we report that an enhancer, located between the promoters of marker of proliferation Ki67 ( MKI67 ) and O6-methylguanine-DNA-methyltransferase ( MGMT ) genes, is activated in TMZ-resistant patient-derived xenograft (PDX) lines and recurrent tumor samples. Activation of the enhancer correlates with increased MGMT expression, a major known mechanism for TMZ resistance. We show that forced activation of the enhancer in cell lines with low MGMT expression results in elevated MGMT expression. Deletion of this enhancer in cell lines with high MGMT expression leads to a dramatic reduction of MGMT and a lesser extent of Ki67 expression, increased TMZ sensitivity, and impaired proliferation. Together, these studies uncover a mechanism that regulates MGMT expression, confers TMZ resistance, and potentially regulates tumor proliferation. Temozolomide (TMZ) resistance in glioblastomas (GBM) is associated with increased MGMT expression. Here, the authors identify an enhancer between the promoters of MKI67 and MGMT , that when activated drives MGMT expression despite MGMT promoter methylation to confer TMZ resistance in GBM.

Objective Nontypeable Haemophilus influenzae (NTHi) plays an important role in respiratory tract infections, and adherence to lung epithelial cells is the first step in lung infections. To explore the role of NTHi in childhood lung infections, a comparative study was conducted on the adherence of strains isolated from sputum culture and bronchoalveolar lavage fluid to A549 lung epithelial cells. Methods Haemophilus influenzae strains were obtained from the sample bank of Shenzhen Children’s Hospital, and identified as NTHi via PCR detection of the capsule gene bex A. NTHi obtained from healthy children’s nasopharyngeal swabs culture were selected as the control group, and a comparative study was conducted on the adherence of strains isolated from sputum culture or bronchoalveolar lavage fluid of patients to A549 cells. Results The adherence bacterial counts of NTHi isolated from the nasopharyngeal cultures of healthy children to A549 cells was 58.2 CFU. In patients with lung diseases, NTHi isolated from bronchoalveolar lavage fluid was 104.3 CFU, and from sputum cultures was 115.1 CFU, both of which were significantly higher in their adherence to A549 cells compared to the strains isolated from the healthy control group. There was no significant difference in adherence between the strains isolated from sputum cultures and bronchoalveolar lavage fluid (t = 0.5217, p  = 0.6033). Conclusion NTHi played an important role in childhood pulmonary infections by enhancing its adherence to lung epithelial cells.

A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Shenzhen. We examined the effect of these measures on the prevalence of respiratory pathogens in children. Clinical and respiratory pathogen data were collected for routine care from hospitalized children with acute respiratory infections in Shenzhen Children’s Hospital from July 2018 to January 2022. Nasopharyngeal swabs were collected and respiratory pathogens were detected using standardized clinical diagnostics as part of routine care. Data were analyzed to describe the effects of COVID-19 prevention procedures on other common pathogens. A total of 56,325 children under 14 years of age were hospitalized with an acute respiratory infection during the study period, 33,909 were tested from July 2018 to January 2020 (pre-lockdown), 1168 from February 2020 to May 2020 (lockdown) and 21,248 from July 2020 to January 2022 (post-lockdown). We observed a 37.3% decline of routine care in respiratory infection associated hospital admission in the 19 months’ post-lockdown vs. the 19 months’ pre-lockdown. There were 99.4%, 16.0% and 1.26% reductions measured for Mycoplasma pneumoniae , influenza virus A and adenovirus, respectively. However, a 118.7% and 75.8% rise was found for respiratory syncytial virus (RSV) and human para-influenza virus (HPIV) during the 19 months’ post-lockdown in comparison to the pre-pandemic period. The detection of RSV especially increased in toddlers after the lockdown. Lockdown measures during the COVID-19 pandemic led to a significant reduction of Mycoplasma pneumoniae, influenza virus A and adenovirus infection. In contrast, RSV and HPIV infection increased.

Oseltamivir is a widely used influenza virus neuraminidase (NA) inhibitor that prevents the release of new virus particles from host cells. However, oseltamivir-resistant strains have emerged, but effective drugs against them have not yet been developed. Elucidating the binding mechanisms between NA and oseltamivir may provide valuable information for the design of new drugs against NA mutants resistant to oseltamivir. Here, we conducted large-scale (353.4 μs) free-binding molecular dynamics simulations, together with a Markov State Model and an importance-sampling algorithm, to reveal the binding process of oseltamivir and NA. Ten metastable states and five major binding pathways were identified that validated and complemented previously discovered binding pathways, including the hypothesis that oseltamivir can be transferred from the secondary sialic acid binding site to the catalytic site. The discovery of multiple new metastable states, especially the stable bound state containing a water-mediated hydrogen bond between Arg118 and oseltamivir, may provide new insights into the improvement of NA inhibitors. We anticipated the findings presented here will facilitate the development of drugs capable of combating NA mutations.

Human Adenovirus (AdV) infection is very common and usually has a significant impact on children. AdV-induced inflammation is believed to be one of the main causes of severe symptoms. However, an inflammatory response profile in the airway in AdV-infected children is still lacking, and the mechanism underlying AdV-induced inflammation in the airway is also poorly understood. In the current study, we determined the expression of a panel of inflammation cytokines in the airway samples from AdV 7 infected children and further investigated the molecular mechanism underlying AdV 7-induced cytokine expression. Our results showed that eight out of 13 tested inflammatory cytokines were significantly increased in nasal washes of AdV 7-infected children comparing to healthy control, with IL-6 showing the highest enhancement. AdV 7 infection of bronchial epithelial cell line and primary airway epithelial cells confirmed that AdV 7 increased IL-6 mRNA and protein expression in an infection dose-dependent manner. Promoter analysis revealed that AdV 7 infection transactivated IL-6 promoter and a NF-κB binding site in IL-6 promoter was involved in the transactivation. Further analysis showed that upon AdV 7 infection, NF-κB p65 was phosphorylated and translocated into nucleus and bound onto IL-6 promoter. Signaling pathway analysis revealed that p38/NF-κB pathway was involved in AdV 7 infection induced IL-6 elevation. Taken together, our study shows that AdV 7 infection triggers the expression of a range of inflammatory cytokines including IL-6 in the airway of infected children, and AdV 7 enhances IL-6 expression by transactivating IL-6 promoter p38/NF-κB signaling pathway. Findings of our current study have provided more information toward a better understanding of AdV-induced airway inflammation, which might also benefit the development of intervention strategies.

Pneumonia is one of the most important causes of morbidity and mortality in children. Identification and characterization of pathogens that cause infections are crucial for accurate treatment and accelerated recovery. However, in most cases, the causative agent cannot be identified, which is partly due to the limited spectrum of pathogens covered by current diagnostics based on nucleic acid amplification. Therefore, in this study, we explored the application of metagenomic next-generation sequencing (mNGS) for the diagnosis of children with severe pneumonia. From April to July 2017, 32 hospitalized children with severe nonresponding pneumonia in Shenzhen Children's Hospital were included in this study. Blood tests were conducted immediately after hospitalization to assess cell counts and inflammatory markers, oropharyngeal swabs were collected to identify common pathogens by qPCR and culture. After bronchoscopy, bronchoalveolar lavage fluid (BALF) samples were collected for further pathogen identification using standardized diagnostic tests and mNGS. Blood tests were normal in 3 of the 32 children. In 9 oropharyngeal swabs, bacterial pathogens were detected, in 5 of these Mycoplasma pneumoniae was detected. Adenovirus was detected in 5 BALF samples, using the Direct Immunofluorescence Assay (DFA). In 15 cases, no common pathogens were found in BALF samples, using the current standard diagnostic tests, while in all 32 BALFs, pathogens were identified using mNGS, including adenovirus, Mycoplasma pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, cytomegalovirus and bocavirus. This study shows that, with mNGS, the sensitivity of detection of the causative pathogens in children with severe nonresponding pneumonia is significantly improved. In addition, mNGS gives more strain specific information, helps to identify new pathogens and could potentially help to trace and control outbreaks. In this study, we have shown that it is possible to have the results within 24 hours, making the application of mNGS feasible for clinical diagnostics.