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Aerosol acidity plays a key role in secondary aerosol formation. The high-temporal-resolution PM2.5 pH and size-resolved aerosol pH in Beijing were calculated with ISORROPIA II. In 2016–2017, the mean PM2.5 pH (at relative humidity (RH) > 30 %) over four seasons was 4.5±0.7 (winter) > 4.4±1.2 (spring) > 4.3±0.8 (autumn) > 3.8±1.2 (summer), showing moderate acidity. In coarse-mode aerosols, Ca2+ played an important role in aerosol pH. Under heavily polluted conditions, more secondary ions accumulated in the coarse mode, leading to the acidity of the coarse-mode aerosols shifting from neutral to weakly acidic. Sensitivity tests also demonstrated the significant contribution of crustal ions to PM2.5 pH. In the North China Plain (NCP), the common driving factors affecting PM2.5 pH variation in all four seasons were SO42-, TNH3 (total ammonium (gas + aerosol)), and temperature, while unique factors were Ca2+ in spring and RH in summer. The decreasing SO42- and increasing NO3- mass fractions in PM2.5 as well as excessive NH3 in the atmosphere in the NCP in recent years are the reasons why aerosol acidity in China is lower than that in Europe and the United States. The nonlinear relationship between PM2.5 pH and TNH3 indicated that although NH3 in the NCP was abundant, the PM2.5 pH was still acidic because of the thermodynamic equilibrium between NH4+ and NH3. To reduce nitrate by controlling ammonia, the amount of ammonia must be greatly reduced below excessive quantities.

Wuhan is dotted with lakes, is known as the “City with Hundreds of Lakes”, and the development of the city is inseparable from the river and lake waters, with the evolution of the lakes affecting the construction and layout of the city. Since the 20th century, the lake evolution in the main urban area of Wuhan has been the most intense and the urban development has also been the most rapid. Therefore, on the basis of the study of the origin of different types of lakes, based on the precious high-precision historical maps of Wuhan in the early- and mid-20th century, combined with the information about lakes in Wuhan obtained from satellite remote sensing images, the evolution characteristics of the lakes in Wuhan in the past 100 years (1920~2019) were investigated through the theory of landscape fractal, and the response mechanism of lake evolution to urban expansion was further explored by being combined with the trajectory of urban expansion. The results show that the area of lakes in Wuhan declined from 2133.5 km2 in 1920 to 550.8 km2 in 2019, with a total decrease of 1582.7 km2, an area shrinkage rate of 74.18%, and a strong amplitude of area change. The changes in the fractal dimension and the shoreline development coefficient of lakes in Wuhan city show synchronization as a whole, with occasional fluctuations, but on the whole, the fractal dimension and shoreline development coefficient of lakes are becoming smaller over a century. Specifically, the evolution of lakes in the Hankou area is mainly affected by the construction of dykes and lake filling, and most of the lakes are resolved and fragmented under the influence of urban expansion, whereas the evolution of lakes in Wuchang and Hanyang is mainly caused by the urban construction around the lakes, and many lake branches have been cut for various urban constructions, and the shape of the lake tends to be simple and regular under the influence of urban expansion. This study is of great significance for filling in the history of lake evolution in Wuhan before the popularization of remote sensing, and for guiding the rational development of lakes in Wuhan and the sustainable and healthy development of Wuhan.

Background Aortic dissection (AD) is a rare but dangerous cardiovascular condition, and research on the health-related quality of life (HRQOL) of postoperative patients after discharge is limited. This study aimed to classify patterns of HRQOL among this population, and to examine the psychological and social factors associated with different HRQOL categories based on the common sense model of self-regulation and the social-cognitive processing model. Methods A cross-sectional study was conducted in two tertiary general hospitals in Wuhan from January 2022 to August 2022. HRQOL was assessed via the validated Patient-Reported Outcomes Measurement Information System 29-item Profile. Characteristic categories of HRQOL were identified through exploratory latent profile analysis. Univariate analysis and multinominal logistic regression were employed to explore the factors associated with HRQOL. Results Among the 379 patients, the mean health utility was 0.36 ± 0.17. A total of 35.4% and 32.5% of the patients had obvious anxiety and depression, respectively. The patients were divided into three HRQOL subgroups: “high psychological distress-pain group” (29.0%), “mild functional impairment-anxiety group” (49.3%), and “mild functional impairment-adaptation group” (21.6%). Significant factors associated with HRQOL included age, AD type, illness cognitive representation, fear of disease progression, daily life management and exercise ( P  < 0.05). Conclusions The self-reported health status of postoperative AD patients is concerning. HRQOL within this population displays significant heterogeneity, and stratified care tailored to each group is recommended. Interventions targeting cognitive representations and fear reduction may enhance HRQOL. Continuous care to facilitate self-management behaviors is essential for improving health outcomes for postoperative AD patients. These findings require further longitudinal and interventional studies to confirm.

Based on published literature and typical profiles from the Nankai University source library, a total of 3326 chemical profiles of the main primary sources of ambient particulate matter (PM) across China from 1987 to 2017 are investigated and reviewed to trace the evolution of their main components and identify the main influencing factors concerning their evolution. In general, the source chemical profiles are varied with respect to their sources and are influenced by different sampling methods. The most complicated profiles are likely attributed to coal combustion (CC) and industrial emissions (IE). The profiles of vehicle emissions (VE) are dominated by organic carbon (OC) and elemental carbon (EC), and vary due to the changing standards of sulfur and additives in gasoline and diesel as well as the sampling methods used. In addition to the sampling methods used, the profiles of biomass burning (BB) and cooking emissions (CE) are also impacted by the different biofuel categories and cooking types, respectively. The variations of the chemical profiles of different sources, and the homogeneity of the subtype source profiles within the same source category are examined using uncertainty analysis and cluster analysis. As a result, a relatively large variation is found in the source profiles of CC, VE, IE, and BB, indicating that these sources urgently require the establishment of local profiles due to their high uncertainties. The results presented highlight the need for further investigation of more specific markers (e.g., isotopes, organic compounds, and gaseous precursors), in addition to routinely measured components, in order to properly discriminate sources. Although the chemical profiles of the main sources have been previously reported in the literature, it should be noted that some of these chemical profiles are currently out of date and need to be updated immediately. Additionally, in the future, specific focus should be placed on the source profile subtypes, especially with respect to local IE in China.

Patients with relapsed or refractory FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia have a poor prognosis, including high frequency of relapse, poorer response to salvage therapy, and shorter overall survival than those with FLT3 wild-type disease. We aimed to assess whether single-agent quizartinib, an oral, highly potent and selective type II FLT3 inhibitor, improves overall survival versus salvage chemotherapy. QuANTUM-R is a randomised, controlled, phase 3 trial done at 152 hospitals and cancer centres in 19 countries. Eligible patients aged 18 years or older with ECOG performance status 0–2 with relapsed or refractory (duration of first composite complete remission ≤6 months) FLT3-ITD acute myeloid leukaemia after standard therapy with or without allogeneic haemopoietic stem-cell transplantation were randomly assigned (2:1; permuted block size of 6; stratified by response to previous therapy and choice of chemotherapy via a phone-based and web-based interactive response system) to quizartinib (60 mg [30 mg lead-in] orally once daily) or investigator's choice of preselected chemotherapy: subcutaneous low-dose cytarabine (subcutaneous injection of cytarabine 20 mg twice daily on days 1–10 of 28-day cycles); intravenous infusions of mitoxantrone (8 mg/m2 per day), etoposide (100 mg/m2 per day), and cytarabine (1000 mg/m2 per day on days 1–5 of up to two 28-day cycles); or intravenous granulocyte colony-stimulating factor (300 μg/m2 per day or 5 μg/kg per day subcutaneously on days 1–5), fludarabine (intravenous infusion 30 mg/m2 per day on days 2–6), cytarabine (intravenous infusion 2000 mg/m2 per day on days 2–6), and idarubicin (intravenous infusion 10 mg/m2 per day on days 2–4 in up to two 28-day cycles). Patients proceeding to haemopoietic stem-cell transplantation after quizartinib could resume quizartinib after haemopoietic stem-cell transplantation. The primary endpoint was overall survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02039726, and follow-up is ongoing. Between May 7, 2014, and Sept 13, 2017, 367 patients were enrolled, of whom 245 were randomly allocated to quizartinib and 122 to chemotherapy. Four patients in the quizartinib group and 28 in the chemotherapy group were not treated. Median follow-up was 23·5 months (IQR 15·4–32·3). Overall survival was longer for quizartinib than for chemotherapy (hazard ratio 0·76 [95% CI 0·58–0·98; p=0·02]). Median overall survival was 6·2 months (5·3–7·2) in the quizartinib group and 4·7 months (4·0–5·5) in the chemotherapy group. The most common non-haematological grade 3–5 treatment-emergent adverse events (within ≤30 days of last dose or >30 days if suspected to be a treatment-related event) for quizartinib (241 patients) and chemotherapy (94 patients) were sepsis or septic shock (46 patients [19%] for quizartinib vs 18 [19%] for chemotherapy), pneumonia (29 [12%] vs eight [9%]), and hypokalaemia (28 [12%] vs eight [9%]). The most frequent treatment-related serious adverse events were febrile neutropenia (18 patients [7%]), sepsis or septic shock (11 [5%]), QT prolongation (five [2%]), and nausea (five [2%]) in the quizartinib group, and febrile neutropenia (five [5%]), sepsis or septic shock (four [4%]), pneumonia (two [2%]), and pyrexia (two [2%]) in the chemotherapy group. Grade 3 QT prolongation in the quizartinib group was uncommon (eight [3%] by central reading, ten [4%] by investigator report); no grade 4 events occurred. There were 80 (33%) treatment-emergent deaths in the quizartinib group (31 [13%] of which were due to adverse events) and 16 (17%) in the chemotherapy group (nine [10%] of which were due to adverse events). Treatment with quizartinib had a survival benefit versus salvage chemotherapy and had a manageable safety profile in patients with rapidly proliferative disease and very poor prognosis. Quizartinib could be considered a new standard of care. Given that there are only a few available treatment options, this study highlights the value of targeting the FLT3-ITD driver mutation with a highly potent and selective FLT3 inhibitor. Daiichi Sankyo.

Disease progression in patients with HER2-positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signalling pathway. We aimed to assess whether the addition of the mTOR inhibitor everolimus to trastuzumab might restore sensitivity to trastuzumab. In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited women with HER2-positive, trastuzumab-resistant, advanced breast carcinoma who had previously received taxane therapy. Eligible patients were randomly assigned (1:1) using a central patient screening and randomisation system to daily everolimus (5 mg/day) plus weekly trastuzumab (2 mg/kg) and vinorelbine (25 mg/m2) or to placebo plus trastuzumab plus vinorelbine, in 3-week cycles, stratified by previous lapatinib use. The primary endpoint was progression-free survival (PFS) by local assessment in the intention-to-treat population. We report the final analysis for PFS; overall survival follow-up is still in progress. This trial is registered with ClinicalTrials.gov, number NCT01007942. Between Oct 26, 2009, and May 23, 2012, 569 patients were randomly assigned to everolimus (n=284) or placebo (n=285). Median follow-up at the time of analysis was 20·2 months (IQR 15·0–27·1). Median PFS was 7·00 months (95% CI 6·74–8·18) with everolimus and 5·78 months (5·49–6·90) with placebo (hazard ratio 0·78 [95% CI 0·65–0·95]; p=0·0067). The most common grade 3–4 adverse events were neutropenia (204 [73%] of 280 patients in the everolimus group vs 175 [62%] of 282 patients in the placebo group), leucopenia (106 [38%] vs 82 [29%]), anaemia (53 [19%] vs 17 [6%]), febrile neutropenia (44 [16%] vs ten [4%]), stomatitis (37 [13%] vs four [1%]), and fatigue (34 [12%] vs 11 [4%]). Serious adverse events were reported in 117 (42%) patients in the everolimus group and 55 (20%) in the placebo group; two on-treatment deaths due to adverse events occurred in each group. The addition of everolimus to trastuzumab plus vinorelbine significantly prolongs PFS in patients with trastuzumab-resistant and taxane-pretreated, HER2-positive, advanced breast cancer. The clinical benefit should be considered in the context of the adverse event profile in this population. Novartis Pharmaceuticals Corporation.

Chronic obstructive pulmonary disease (COPD) is an inflammatory respiratory disease. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of COPD. In the present study, we set to investigate the role and mechanism of LOC729178 on cigarette smoke extract (CSE)-induced inflammatory damage in 16HBE cells. The expression levels of LOC729178, miR-144-3p, and PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. Enzyme-linked immunosorbent assay (ELISA) assay was performed to evaluate the levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and IL-8. Targeted relationships among LOC729178, miR-144-3p, and PHLPP2 were verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Our data indicated that LOC729178 was underexpressed in COPD tissues and CSE-treated 16HBE cells. Exogenous expression of LOC729178 alleviated CSE-induced inflammatory injury in 16HBE cells. LOC729178 targeted miR-144-3p by directly binding to miR-144-3p. miR-144-3p was a downstream effector of LOC729178 function. PHLPP2 was identified as a direct and functional target of miR-144-3p. Furthermore, LOC729178 operated as a post-transcriptional regulator of PHLPP2 expression through miR-144-3p. Our current study suggested that LOC729178 overexpression alleviated CSE-induced inflammatory injury in 16HBE cells at least in part by up-regulating PHLPP2 via sponging miR-144-3p, providing a rationale for developing LOC729178 as a potential therapeutic agent against COPD.

Precise regulation of type I interferon signaling is crucial for effective immune defense against infectious diseases. However, the molecular mechanisms governing this pathway are not fully understood. Here, we show a function for palmitoylation in enhancing anti-malarial immune responses. Our findings reveal that ZDHHC9 enhances the type I interferon signaling by palmitoylating TBK1 at cysteine 292. Following infection with Plasmodium yoelii N67, the delicate balance between palmitoylation and depalmitoylation of TBK1 is disrupted. Specifically, upregulation of APT2 promotes persistent depalmitoylation of TBK1 and triggers its selective autophagic degradation via K48-linked polyubiquitination at lysine 251/372 by E3 ligase TRIM27. This process acts as a recognition signal for the cargo receptor NDP52, resulting in inhibition of the type I interferon pathway. Notably, inhibition of APT2 using ML349 elevates type I interferon levels and improves survival rates against N67 infection. Here, we show that targeting APT2-mediated TBK1 depalmitoylation is a potential therapeutic strategy for malaria and may also be applicable to other diseases driven by dysregulated type I interferon signaling. Anti-malarial immune responses involve type I IFN responses and innate immune pathways. Here the authors show the palmitoylation of TANK-binding kinase 1 (TBK1), a kinase which promotes the type I IFN pathway, is disrupted in malaria infection and that this disruption leads to less effective anti-malarial responses.

In this study we have considered the three dimensional corrective forces for correction of scoliosis by using a patient specific finite element model. An objective function of corrective forces in three-dimensional space was defined. Computed tomography images were used to reconstruct three dimensional model of scoliotic trunk. Computer aided engineering software Abaqus was used to establish finite element model of deformed spine and its biomechanical characteristics were analyzed. By adjusting magnitude and position of corrective forces, objective function was minimized to achieve best orthopedic effect. The proposed corrective conditions were divided into three groups: (1) thoracic deformity; (2) lumbar deformity; (3) both thoracic and lumbar deformities were considered. In all three cases, the objective function was reduced by 58, 52, and 63%, respectively. The best correction forces point was located on convex side of maximum displacement of vertebral body. Using minimum objective function method, spinal deformity in three-dimensional space can be sufficiently reduced. This study provides scientific basis for design of a new corrective brace for treatment of scoliosis.

The aim of this study was to investigate the effects of different preservatives and drying methods on the nutrient composition and mould counts of oat hay and oat pellets. Oat hay and oat pellets were divided into 5 groups: CON (without additives, control), CAP (with 5% calcium propionate), CUR (with 5% curcumin), SKU (with 5% Scutellaria baicalensis ) and KC (with 2% potassium carbonate). The nutrients and mould counts of each group were determined after air drying, drying at 50 °C and drying at 50 °C with forced air for 48 h and 96 h, respectively. Compared with air drying, drying at 50 °C and drying at 50 °C with forced air significantly increased the dry matter content of oat. Under different drying times and methods, the addition of preservatives at air-drying for 96 h was more effective at improving the crude protein content of oat hay but was not positive for oat pellets. In addition, under different drying times and methods, the addition of preservatives to oat hay dried at 50 °C for 48 h was more effective at reducing the contents of neutral detergent fibres and acidic detergent fibres. The addition of CUR to oat pellets dried at 50 °C was the most effective at reducing the neutral and acidic detergent fibres of oat pellets. Under different drying times and methods, the addition of preservatives during air drying and drying at 50 °C for 48 h was more effective in reducing mould counts in oat hay and oat pellets. In addition, CUR resulted in higher CP contents and lower mould counts not only in oat hay dried at 50 °C for 48 h but also in oat pellets air dried for 48 h, which indicates its potential use in oat hay production.