Activable Nano-Immunomodulator Assembled from π-Extended Naphthalenediimide for Precision Photothermal Immunotherapy.

A nano-immunomodulator (R-NPT NP) comprising a tumor microenvironment (TME) activable resiquimod (R848) and a π-extended NIR-absorbing naphthophenanthrolinetetraone (NPT) has been engineered for spatiotemporal controlled photothermal immunotherapy. R-NPT NP demonstrated excellent photostability, while R848 promoted synergistic immunity as a toll-like receptor 7/8 (TLR7/8) agonist. Upon accumulation at the tumor site, R-NPT NP released R848 in response to redox metabolite glutathione (GSH), triggering dendritic cell (DC) activation. The photothermal effect endowed by R-NPT NP can ablate tumors directly and trigger immunogenic cell death to augment immunity after photoirradiation. The synergistic effect of GSH-liable TLR7/8 agonist and released immunogenic factors leads to a robust evocation of systematic immunity through promoted DC maturation and T cell infiltration. Thus, R-NPT NP with photoirradiation achieved 99.3% and 98.2% growth inhibition against primary and distal tumors, respectively.

Atomic Imaging of Multi-Dimensional Ruddlesden-Popper Interfaces in Lead-Halide Perovskites.

Ruddlesden-Popper (RP) interface with defined stacking structure will fundamentally influence the optoelectronic performances of lead-halide perovskite (LHP) materials and devices. However, it remains challenging to observe the atomic local structures in LHPs, especially for multi-dimensional RP interface hidden inside the nanocrystal. In this work, the advantages of two imaging modes in scanning transmission electron microscopy (STEM), including high-angle annular dark field (HAADF) and integrated differential phase contrast (iDPC) STEM, are successfully combined to study the bulk and local structures of inorganic and organic/inorganic hybrid LHP nanocrystals. Then, the multi-dimensional RP interfaces in these LHPs are atomically resolved with clear gap and blurred transition region, respectively. In particular, the complex interface by the RP stacking in 3D directions can be analyzed in 2D projected image. Finally, the phase transition, ion missing, and electronic structures related to this interface are investigated. These results provide real-space evidence for observing and analyzing atomic multi-dimensional RP interfaces, which may help to better understand the structure-property relation of LHPs, especially their complex local structures.

Unraveling the Molecular Size Effect on Surface Engineering of Perovskite Solar Cells.

Surface engineering in perovskite solar cells, especially for the upper surface of perovskite, is widely studied. However, most of these studies have primarily focused on the interaction between additive functional groups and perovskite point defects, neglecting the influence of other parts of additive molecules. Herein, additives with -NH3 + functional group are introduced at the perovskite surface to suppress surface defects. The chain lengths of these additives vary to conduct a detailed investigation into the impact of molecular size. The results indicate that the propane-1,3-diamine dihydroiodide (PDAI2 ), which possesses the most suitable size, exhibited obvious optimization effects. Whereas the molecules, methylenediamine dihydroiodide (MDAI2 ) and pentane-1,5-diamine dihydroiodide (PentDAI2 ) with unsuitable size, lead to a deterioration in device performance. The PDAI2 -treated devices achieved a certified power conversion efficiency (PCE) of 25.81% and the unencapsulated devices retained over 80% of their initial PCE after 600 h AM1.5 illumination.

Atomic Imaging of the Pb Precipitation in Lead-Halide Perovskites.

The lead iodide (PbI2 ) in lead-halide perovskite (LHP) is both a positive additive for material properties and a site for the formation of device defects. Therefore, atomic-level detection of PbI2 and its derived Pb structures are crucial for understanding the performance and stability of the LHP material. In this work, the atomic imaging of the LHP, PbI2 , and Pb lattices is achieved using low-dose integrated differential phase contrast (iDPC) scanning transmission electron microscopy (STEM). Combining it with the traditional high-angle annular dark field (HAADF)-STEM, the Pb precipitation in different LHPs (CsPbI3 , CsPbBr3, and FAPbI3 ) and under different conditions (light, air, and heat) can be investigated in real space. Then, the features of Pb precipitation (positions and sizes) are visually revealed under different conditions and the stabilities of different LHPs. Meanwhile, the pathway of Pb precipitation is directly imaged and confirmed by the iDPC-STEM during an in situ heating process, supporting the detailed mechanism of Pb precipitation. These results provide the visual evidence for analyzing atomic Pb precipitation in LHPs, which helps better understand the structure-property relation induced by Pb impurity.

Bloqueadores de los canales de calcio frente a otras clases de fármacos para la hipertensión: una revisión Cochrane / Calcium channel blockers versus other classes of drugs for hypertension: a Cochrane review

¿Cuál es el objetivo de esta revisión? En esta primera actualización de una revisión publicada en 2010. Se pretendía averiguar si los bloqueadores de los canales del calcio (BCC) pueden prevenir eventos cardiovasculares perjudiciales, como el ictus, el infarto de miocardio y la insuficiencia cardiaca, en comparación con otros antihipertensivos (hipotensores) utilizados en personas con presión arterial elevada (hipertensión). Fundamento. La disminución adecuada de la presión arterial elevada en personas con hipertensión puede reducir la cantidad de complicaciones importantes de la hipertensión, como el ictus, el infarto de miocardio, la insuficiencia cardiaca congestiva e incluso la muerte. Los BCC se utilizan como medicación de primera línea para reducir la presión arterial, pero se ha debatido si esta es la mejor forma de reducir los eventos cardiovasculares nocivos. Fecha de búsqueda. La evidencia está actualizada hasta el 1 de septiembre de 2020. Características del estudio. Se encontraron 23 estudios relevantes realizados en Europa, Norteamérica, Oceanía, Israel y Japón. Los estudios compararon el tratamiento con tratamiento con BCC frente al tratamiento con otras clases de fármacos hipotensores en personas con hipertensión e incluyeron 153.849 participantes. El seguimiento de los participantes en los ensayos osciló entre 2 y 5,3 años. Resultados clave. No hubo diferencias en las muertes por todas las causas entre los BCC y otros fármacos hipotensores. Los diuréticos probablemente reducen los eventos cardiovasculares totales y la insuficiencia cardiaca congestiva más que los BCC. Los BCC probablemente reducen los eventos cardiovasculares totales más que los bloqueadores beta... (AU)

Implication of m6A Methylation Regulators in the Immune Microenvironment of Bronchopulmonary Dysplasia.

N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of bronchopulmonary dysplasia (BPD) remains poorly characterized. Thus, the purpose of this investigation was to evaluate the effects of m6A RNA methylation regulators on the development of BPD. BPD-related transcriptome data were downloaded from the GEO database. Differentially expressed m6A methylation regulators between BPD and control group were identified. Consensus clustering was conducted for the classification of BPD and association between clusters and BPD phenotypes were explored. Analysis of differentially expressed genes (DEGs) and immune-related DEGs was performed. The GSEA, GO and KEGG analyses were used to interpret the functional enrichments. The composition of immune cell subtypes in BPD subsets was predicted by CIBERSORT analysis. Compared with the control group, expression of most m6A regulators showed significant alteration, especially for IGF2BP1/2/3. BPD was classified into 2 subsets, and cluster 1 was correlated with severe BPD. Furthermore, the results of functional enrichment analyses showed a disturbed immune-related signaling pathway. Based on CIBERSORT analysis, we found that the proportion of immune cell subsets changed between cluster 1 and cluster 2. Our study revealed the implication of m6A methylation regulators in the development of BPD, which might provide a novel insight for the diagnosis and treatment of BPD.

Bloqueadores de los canales de calcio frente a otras clases de fármacos para la hipertensión: una revisión Cochrane / Calcium channel blockers versus other classes of drugs for hypertension: a Cochrane review

¿Cuál es el objetivo de esta revisión? En esta primera actualización de una revisión publicada en 2010. Se pretendía averiguar si los bloqueadores de los canales del calcio (BCC) pueden prevenir eventos cardiovasculares perjudiciales, como el ictus, el infarto de miocardio y la insuficiencia cardiaca, en comparación con otros antihipertensivos (hipotensores) utilizados en personas con presión arterial elevada (hipertensión). Fundamento. La disminución adecuada de la presión arterial elevada en personas con hipertensión puede reducir la cantidad de complicaciones importantes de la hipertensión, como el ictus, el infarto de miocardio, la insuficiencia cardiaca congestiva e incluso la muerte. Los BCC se utilizan como medicación de primera línea para reducir la presión arterial, pero se ha debatido si esta es la mejor forma de reducir los eventos cardiovasculares nocivos. Fecha de búsqueda. La evidencia está actualizada hasta el 1 de septiembre de 2020. Características del estudio. Se encontraron 23 estudios relevantes realizados en Europa, Norteamérica, Oceanía, Israel y Japón. Los estudios compararon el tratamiento con tratamiento con BCC frente al tratamiento con otras clases de fármacos hipotensores en personas con hipertensión e incluyeron 153.849 participantes. El seguimiento de los participantes en los ensayos osciló entre 2 y 5,3 años. Resultados clave. No hubo diferencias en las muertes por todas las causas entre los BCC y otros fármacos hipotensores. Los diuréticos probablemente reducen los eventos cardiovasculares totales y la insuficiencia cardiaca congestiva más que los BCC. Los BCC probablemente reducen los eventos cardiovasculares totales más que los bloqueadores beta... (AU)

Weakened black carbon trans-boundary transport to the Tibetan Plateau during the COVID-19 pandemic.

The lockdowns implemented during the coronavirus disease 2019 (COVID-19) pandemic provide a unique opportunity to investigate the impact of emission sources and meteorological conditions on the trans-boundary transportation of black carbon (BC) aerosols to the Tibetan Plateau (TP). In this study, we conducted an integrative analysis, including in-situ observational data, reanalysis datasets, and numerical simulations, and found a significant reduction in the trans-boundary transport of BC to the TP during the 2020 pre-monsoon season as a result of the lockdowns and restrictive measures. Specifically, we observed a decrease of 0.0211 µgm-3 in surface BC concentration over the TP compared to the 2016 pre-monsoon period. Of this reduction, approximately 6.04 % can be attributed to the decrease in emissions during the COVID-19 pandemic, surpassing the 4.47 % decrease caused by changes in meteorological conditions. Additionally, the emission reductions have weakened the trans-boundary transport of South Asia BC to the TP by 0.0179 µgm-2s-1; indicating that the recurring spring atmospheric pollution from South Asia to the TP will be alleviated through the reduction of anthropogenic emissions. Moreover, it is important to note that BC deposition on glaciers contributes significantly to glacier melting due to its enrichment, posing a threat to the water sustainability of the TP. Therefore, urgent measures are needed to reduce emissions from adjacent regions to preserve the TP as the "Asian Water Tower."

Effect of Zinc Amino Acid Complexes on Growth Performance, Tissue Zinc Concentration, and Muscle Development of Broilers.

The present study aimed to evaluate the effects of zinc amino acid complexes on growth performance, tissue zinc concentration, and muscle development in broilers. A total of 504 day-old male arbor acres broilers were randomly divided into seven treatments (fed with a basal diet or a basal diet supplemented with 120 mg kg-1 Zn as ZnSO4, 30, 60, 90 or 120 mg kg-1 Zn as ZnN, or 30 mg kg-1 Zn as ZnA separately). Each group had six replicates, with 12 birds per replicate. The results showed that the addition of 60 mg kg-1 ZnN significantly increased (P < 0.05) the average daily gain (ADG) and breast muscle percentage of broilers. Zinc concentration of ZnN and ZnA added groups were higher than (P < 0.05) that in the Zn sulfate group under the same addition dose. Except for the 30 mg kg-1 ZnN group, the muscle fiber diameter and cross-sectional area (CSA) were significantly increased (P < 0.05) in the ZnN addition groups. Compared with the basal diet group, adding ZnN significantly increased (P < 0.05) the expression of MTOR, MYOD, and MYOG at day 21 and decreased (P < 0.05) the expression of Atrogin-1. The expression levels of AKT, MTOR, P70S6K, and MYOD were increased at day 42, while the expression levels of MuRF1 and Atrogin-1 were decreased. Adhesion, backbone regulation of actin, MAPK, mTOR, and AMPK were significantly enriched as indicated by KEGG pathway enrichment analysis. In conclusion, zinc amino acid complexes could improve growth performance, tissue zinc concentration, and regulate breast muscle development.

Endovascular thrombectomy for acute ischemic stroke in elderly patients with large ischemic cores.

BACKGROUND: Understanding the benefits and risks of endovascular therapy (EVT) is crucial for elderly patients with large ischemic cores, as the combination of advanced age and extensive brain infarction may negatively impact clinical outcomes. METHODS: The study retrospectively analyzed clinical outcomes for elderly stroke patients (age ≥ 70) with large ischemic cores (Alberta Stroke Program Early CT Score [ASPECTS] < 6 or ischemic cores ≥ 70 ml) in the anterior circulation using data from our prospective database between June 2018 and January 2022. The effectiveness and risks of EVT in those patients were investigated, with the primary outcome being fair outcome (modified Rankin Scale, mRS ≤ 3). RESULTS: Among 182 elderly patients with large ischemic core volume (120 in the EVT group and 62 in the non-EVT group), 20.9% (38/182, 22.5% in the EVT group vs. 17.7% in the non-EVT group) achieved a fair outcome. Meanwhile, 49.5% (90/182, 45.8% in the EVT group vs. 56.5% in the non-EVT group) of them died at 3 months. The benefits of EVT numerically exceeded non-EVT treatment for those aged ≤ ~ 85 years or with a mismatch volume ≥ ~ 50 ml. However, after adjustment, EVT was associated with an increased risk of symptomatic intracranial hemorrhage (aOR 4.24, 95%CI 1.262-14.247). CONCLUSIONS: This study highlights the clinical challenges faced by elderly patients with large infarctions, resulting in poor outcomes at 3 months. EVT may still provide some benefits in this population, but it also carries an increased risk of intracranial hemorrhage.

Establishment of a juvenile mouse asthma model induced by postnatal hyperoxia exposure combined with early OVA sensitization.

Objective: To establish a juvenile mouse asthma model by postnatal hyperoxia exposure combined with early ovalbumin (OVA) sensitization. Methods: Female C57BL/6J newborn mice were exposed to hyperoxia (95 % O2) from postnatal day-1 (PND1) to PND7; intraperitoneally injected with OVA suspension on PND21, PND28; and stimulated by nebulized inhalation of 1 % OVA from PND36 to PND42. Within 48 h of the last challenge, we observed their activity performance and evaluated airway responsiveness (AHR). All mice were executed at PND44. Female (n = 32) were divided into four groups as follows: room air（RA）+phosphate-buffered saline (PBS) group; O2 (hyperoxia, 95 % O2) + PBS group; RA + OVA group; O2+OVA group. We obtained the serum, bronchoalveolar lavage fluid (BALF), and lung tissues. The Wright-Giemsa staining was performed for leukocyte classification in BALF and HE staining for pathological examination. The levels of IL-2, IL-5, IL-13, IL-17A and IL-10 in BALF and tIgE and sIgE in serum were detected by ELISA. Results: Compared with OVA sensitization or hyperoxia exposure alone, the mice in the model group (O2+OVA) showed asthma-like symptoms and increased airway hyperreactivity,The levels of IL-5,IL-13 IL-17A were increased in BLAF,and total leukocyte and eosinophil counts were also significant increasesed. The levels of tIgE and sIgE in serum were increased. Conclusion: Postnatal hyperoxia exposure combined with early OVA sensitization might establish a juvenile mouse asthma model.

In situ imaging of the atomic phase transition dynamics in metal halide perovskites.

Phase transition dynamics are an important concern in the wide applications of metal halide perovskites, which fundamentally determine the optoelectronic properties and stabilities of perovskite materials and devices. However, a more in-depth understanding of such a phase transition process with real atomic resolution is still limited by the immature low-dose electron microscopy and in situ imaging studies to date. Here, we apply an emergent low-dose imaging technique to identify different phase structures (α, ß and γ) in CsPbI3 nanocrystals during an in-situ heating process. The rotation angles of PbI6 octahedrons can be measured in these images to quantitatively describe the thermal-induced phase distribution and phase transition. Then, the dynamics of such a phase transition are studied at a macro time scale by continuously imaging the phase distribution in a single nanocrystal. The structural evolution process of CsPbI3 nanocrystals at the particle level, including the changes in morphology and composition, is also visualized with increasing temperature. These results provide atomic insights into the transition dynamics of perovskite phases, indicating a long-time transition process with obvious intermediate states and spatial distribution that should be generally considered in the further study of structure-property relations and device performance.

Recruitment of PVT1 Enhances YTHDC1-Mediated m6A Modification of IL-33 in Hyperoxia-Induced Lung Injury During Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that specifically affects preterm infants. Oxygen therapy administered to treat BPD can lead to hyperoxia-induced lung injury, characterized by apoptosis of lung alveolar epithelial cells. Our epitranscriptomic microarray analysis of normal mice lungs and hyperoxia-stimulated mice lungs revealed elevated RNA expression levels of IL-33, as well as increased m6A RNA methylation levels of IL-33 and PVT1 in the hyperoxia-stimulated lungs. This study aimed to investigate the role of the PVT1/IL-33 axis in BPD. A mouse model of BPD was established through hyperoxia induction, and lung histological changes were assessed by hematoxylin-eosin staining. Parameters such as radial alveolar count and mean chord length were measured to assess lung function. Mouse and human lung alveolar epithelial cells (MLE12 and A549, respectively) were stimulated with hyperoxia to create an in vitro BPD model. Cell apoptosis was detected using Western blotting and flow cytometry analysis. Our results demonstrated that silencing PVT1 suppressed apoptosis in MLE12 and A549 cells and improved lung function in hyperoxia-stimulated lungs. Additionally, IL-33 reversed the effects of PVT1 both in vivo and in vitro. Through online bioinformatics analysis and RNA-binding protein immunoprecipitation assays, YTHDC1 was identified as a RNA-binding protein (RBP) for both PVT1 and IL-33. We found that PVT1 positively regulated IL-33 expression by recruiting YTHDC1 to mediate m6A modification of IL-33. In conclusion, silencing PVT1 demonstrated beneficial effects in alleviating BPD by facilitating YTHDC1-mediated m6A modification of IL-33. Inhibition of the PVT1/IL-33 axis to suppress apoptosis in lung alveolar epithelial cells may hold promise as a therapeutic approach for managing hyperoxia-induced lung injury in BPD.

Case of Congenital Hemolytic Anemia with ATP11C and ANK1 Variants.

A male infant of Han descent, with a G1P1 mother and gestational age of 40+4 weeks, was born via cesarean section owing to his mother having pregnancy complications, including premature rupture of membranes, chorioamnionitis, and gestational diabetes. On the first day after birth, routine blood examination showed that his total red blood cells count was 2.32 × 1012/L, hemoglobin count was 77 g/L, and C-reactive protein count was 48.99 mg/L. After receiving an anti-infection treatment for 10 days and two blood transfusions (100 mL in total), he was discharged from a neonatal intensive care unit (NICU). Accessory examinations showed that reticulocytes in the peripheral blood were significantly increased, the morphology of red blood cells was normal, and all hemolysis-related examinations were normal; bone marrow examinations showed that the proliferation of the red blood cell system was low and serum ferritin and vitamin B12 levels were elevated. Because of the unexplained hemolysis, a whole-exome sequencing examination was performed. The results showed a hemizygous variant of the ATP11C gene (c.3136a>t/p ile 1046phe) and a frame-shift variant of the ANK1 gene (c.937del/pala313 leufs*19). After a six-month follow-up, the serum ferritin and vitamin B12 levels had gradually decreased to normal levels, and hemoglobin and reticulocyte values were 97 g/L and 7.17%, respectively, in the peripheral blood. No splenomegaly was found in physical examination.

Effects of combined natural synergists and chemical inhibitors on yield, nitrogen utilization and balance in wheat/maize rotation system.

Urease inhibitors and nitrification inhibitors can enhance nitrogen (N) fertilizer utilization efficiency and reducing N losses through regulating urea-N transformation. Common urease or nitrification inhibitors, however, are predominantly chemically synthesized and high-cost. Furthermore, their inhibitory effects are mediated by soil pro-perties, climatic conditions, and crop systems. In this study, we conducted a field experiment using natural synergists humic acid/zeolite, along with chemical nitrification inhibitor dicyandiamide (DCD) and their combination to elucidate the impacts of natural synergists combined with chemical inhibitors on annual yield, nitrogen utilization efficiency, soil nitrate-N accumulation, and nitrogen balance within the wheat/maize rotation system. The treatments included no nitrogen fertilizer application (CK), single application of urea (N), urea +DCD (ND), urea + humic acid (NH), urea + zeolite (NP), urea + urease inhibitor N-butylthiophosphoric triamide + DCD (NUD), urea + humic acid + DCD (NHD), and urea + zeolite + DCD (NPD). The results showed that, compared to the treatments NH and NP, the integration of humic acid or zeolite with DCD (NHD and NPD) significantly increased maize yield (11268 and 11397 kg·hm-2) and total annual yield (20494 and 20582 kg·hm-2), which were comparable to those of combined chemical urease and nitrification inhibitors (NUD). The NHD and NPD treatments had higher nitrogen utilization efficiency and lower soil nitrate-N accumulation in 80-100 cm soil layer across all seasons relative to the N treatment, which had no significant difference compared to the NUD treatment. Furthermore, a decline in soil nitrogen surplus by 10.7% and 13.9% was observed when comparing the NHD and NPD treatments with the NH and NP treatments, respectively. These findings suggested that combined humic acid or zeolite and chemical nitrification inhibitors could effectively enhance crop yield and N utilization efficiency and meet the requirements of the green and environmental preservation of modern agriculture.

A nomogram predicts early neurological deterioration after mechanical thrombectomy in patients with ischemic stroke.

Introduction: Early neurological deterioration (END) is common in acute ischemic stroke and is directly associated with poor outcome after stroke. Our aim is to develop and validate a nomogram to predict the risk of END after mechanical thrombectomy (MT) in acute ischemic stroke patients with anterior circulation large-vessel occlusion. Methods: We conducted a real-world, multi-center study in patients with stroke treated with mechanical thrombectomy. END was defined as a worsening by 2 or more NIHSS points within 72-hour after stroke onset compared to admission. Multivariable logistic regression was used to determine the independent predictors of END, and the discrimination of the scale was assessed using the C-index. Calibration curves were constructed to evaluate the calibration of the nomogram, and decision curves were used to describe the benefits of using the nomogram. Results: A total of 1007 patients were included in our study. Multivariate logistic regression analysis found age, admission systolic blood pressure, initial NIHSS scores, history of hyperlipemia, and location of occlusion were independent predictors of END. We developed a nomogram that included these 6 factors, and it revealed a prognostic accuracy with a C-index of 0.678 in the derivation group and 0.650 in the validation group. The calibration curves showed that the nomogram provided a good fit to the data, and the decision curves demonstrated a large net benefit. Discussion: Our study established and validated a nomogram to stratify the risk of END before mechanical embolectomy and identify high-risk patients, who should be more cautious when making clinical decisions.

Hormone effects of eighteen bisphenol analogues and their effects on cellular homeostasis and the typical signal pathways.

Through the transfer chain of surroundings from feed to the farmed-animals and ultimately the corresponding livestock and poultry products, people are exposed to large amounts of bisphenol analogues (BPs), such as rational emissions from manufacturing plants, feed packaging bags and food packaging contact. Some BPs have been reported to show certain toxicological effects, especially, estrogen and endocrine disrupting effect. With the increasing application of BPs, the problem is becoming more and more serious. We systematically studied the hormonal effects of 18 BPs and their effects on cell homeostasis and classical signaling pathways by using classical E-SCREEN assay, fluorescent probes and western blotting. The results confirmed the estrogen-like effect of 13 BPs and 6 BPs obtained high docking scores (Scores < -9.0) for the three receptors simultaneously with the main interactions of hydrophobic, hydrogen and π-stacking of T-type bonds. BPAP regulates cells via apoptosis and steroid signaling pathway by intracellular ROS and mitochondrial followed the caspase pathway. BPE and BPS were involved in the classical NF-κB and Hippo signaling pathways. All data provides scientific basis for the safety risk assessment of endocrine disrupting and cellular homeostasis evaluation of BPs as chronic environmental pollution.

Cryptotanshinone affects HFL-1 cells proliferation by inhibiting cytokines secretion in RAW264.7 cells and ameliorates inflammation and fibrosis in newborn rats with hyperoxia induced lung injury.

Objective: Bronchopulmonary dysplasia (BPD) is a common complication of prematurity and has no specific treatment option. Moreover, inflammation and fibrosis play a vital role in the development of BPD. Thus, this study aimed to explore the role of the anti-inflammatory and anti-fibrotic drug cryptotanshinone (CTS) in the treatment of inflammation and fibrosis in BPD. Methods: In vivo, Sprague-Dawley rats (male) were divided into air, hyperoxia and CTS groups with different dose interventions (7.5, 15, and 30 mg/kg). A BPD rat model was induced by continuous inhalation of hyperoxia (95%) for 7 days, during which different doses of CTS were injected intraperitoneally. Furthermore, histological examination, hydroxyproline content measurement, Western blot and real-time quantitative polymerase chain reaction were used to detect the levels of inflammation and fibrosis in the tissues. RAW264.7 cells exposed to 95% oxygen were collected and co-cultured with fibroblasts to determine the expression levels of α-SMA, collagen-Ⅰ and MMPs. The levels of pro-inflammatory cytokines such as TNF-α, IL-6 and pro-fibrotic factor TGF-ß1 in the supernatants were measured using enzyme-linked immunosorbent assay. Results: Haematoxylin and eosin staining revealed that CTS reduced the inflammatory response in rat lungs. Masson staining revealed that CTS alleviated the level of pulmonary fibrosis. CTS also reduced the levels of TNF-α, IL-6 and TGF-ß1 along with the expression of the fibrosis marker α-SMA in lung tissue. Similarly, in vitro analysis revealed that CTS decreased the levels of TNF-α, IL-6 and TGF-ß1 expressed in RAW 264.7 cells, and reduced α-SMA, collagen-Ⅰ, MMPs concentrations in HFL-1 cells co-cultured with the supernatant of RAW264.7 cells after hyperoxia. Conclusion: CTS can attenuate the hyperoxia-induced inflammatory response and the level of fibrosis by regulating the levels of inflammatory factors and fibrotic factor TGF-ß1 expressed by macrophages, thereby highlighting the therapeutic potential of CTS in the treatment of BPD.

Effects of early postnatal hyperoxia exposure combined with early ovalbumin sensitization on lung inflammation and bacterial flora in a juvenile mouse model of asthma.

Objective: The aim of this study is to explore the effects of early postnatal hyperoxia exposure combined with early ovalbumin (OVA) sensitization on lung inflammation and bacterial flora in neonatal mice on a juvenile mouse model of asthma. Methods: Thirty-two newborn female C57BL/6 J mice were randomly divided into four groups, which including room air+phosphate-buffered saline (PBS) group, hyperoxia+PBS group, room air+OVA group, and hyperoxia+OVA group, according to the hyperoxia exposure and/or OVA induction. Mice were exposed to either 95% O2 or room air for 7 days after birth; after 7 days, they were exposed to air and received an intraperitoneal injection of OVA suspension or PBS solution on postnatal days 21 (P21) and 28 (P28). From P36 to P42, the mice were allowed to inhale of 1% OVA or 0.9% NaCl solution. The mice were observed after the last excitation. HE staining was performed to observe the pathological changes in lung tissues. Wright-Giemsa staining was used to perform bronchoalveolar lavage fluid (BALF) leukocyte sorting. Enzyme-linked immunosorbent assay was used to determined the cytokines levels of interleukin (IL)-2, IL-5, IL-13, IL-17A, and IL-10 and serum IgE levels in BALF. Additionally, 16S rRNA sequencing was used to analyze the characteristics of lung microbiota. Results: Mice in the hyperoxia+OVA group showed asthma-like symptoms. HE staining results revealed a significant thickening of the airway wall and airway inflammation. BALF analysis of cellular components showed significant increases in total leukocyte and eosinophil counts and the levels of cytokines related to Th2 (IL-5 and IL-13) and Th17 (IL-17A); 16S rRNA sequencing revealed that the main members of the pulmonary microflora were Actinobacteriota, Proteobacteria, Firmicutes, and Bacteroidota at the phylum level. In addition, the bacteria with a major role were Acinetobacter and Moraxellaceae in the O2 + OVA group. Conclusion: The mouse suffering from postnatal hyperoxia exposure and early OVA sensitization, changes in symptoms, pathology, leukocyte and eosinophil counts, and levels of different T-cell cytokines in BALF and lung microbiota, which may provide a basis for the establishment of a juvenile mouse model of asthma.

The Role of "Hierarchical and Classified Prevention and Control Measures (HCPC)" Strategy for SARS-CoV-2 Delta Variant in Guangzhou: A Modeling Study.

BACKGROUND: The Delta variant of SARS-COV-2 has replaced previously circulating strains around the world in 2021. Sporadic outbreaks of the Delta variant in China have posed a concern about how to properly respond to the battle against evolving COVID-19. Here, we analyzed the "hierarchical and classified prevention and control (HCPC)" measures strategy deployed during the recent Guangzhou outbreak. METHODS: A modified susceptible-exposed-pre-symptomatic-infectious-recovered (SEPIR) model was developed and applied to study a range of different scenarios to evaluate the effectiveness of policy deployment. We simulated severe different scenarios to understand policy implementation and timing of implementation. Two outcomes were measured: magnitude of transmission and duration of transmission. The outcomes of scenario evaluations were presented relative to the reality case (i.e., 368 cases in 34 days) with 95% confidence interval (CI). RESULTS: Based on our simulation, the outbreak would become out of control with 7 million estimated infections under the assumption of the absence of any interventions than the 153 reported cases in reality in Guangzhou. The simulation on delayed implementation of interventions showed that the total case numbers would also increase by 166.67%-813.07% if the interventions were delayed by 3 days or 7 days. CONCLUSIONS: It may be concluded that timely and more precise interventions including mass testing and graded community management are effective measures for Delta variant containment in China.