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Based on the concept of “passengers self-help hubbing,” we build a flight schedule optimization model where maximizing the number of feasible flight connections, indicating transfer opportunities, as one objective and minimizing total slot displacements as the other objective. At the same time, the “Demand Smoothing Model” is introduced into the flight schedule optimization model to reduce the queuing delays for arrival and departure flights. We take into account all aircraft itineraries, the difficulty level of schedule coordination, and the maximum displacement of any single flight acceptable to airlines when optimizing flight schedule. Given an original schedule, the model produces a feasible modified schedule that obeys the slot limits specified for an airport without canceling any flights, increases transfer opportunities, and improves on-time performance for hub airports while reducing interference with airline scheduling preferences. The model was verified with the operating data of the Urumqi international airport, and the results show that minor adjustments to flight schedules can increase the transfer opportunities of the airport and significantly reduce flight queuing delays.

ObjectiveTo analysed nutritious and harmful elements found in liquid milk marketed in different regions across China, analyzed the intake of elements from drinking milk, assessed exposure to elements and health risks in adults, and provided basis for relevant standards.MethodsAs many as 110 milk samples were collected in seven geographic regions across China. A total of 15 elements, Mg, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd and Pb, were determined with microwave digestion - inductively coupled plasma mass spectrometry to analyze regional differences. Recommended Nutrient Intake (RNI) and Adequate Intake (AI) were used to assess nutrition status while Margin of Exposure (MOE) and Provisional Tolerable Monthly Intake (PTMI) were used to assess health risks.ResultsThe result showed that milk generally has high level of Ca (430-939 mg/kg). The levels of 9 elements, namely Fe, Cr, Co, Mn, V, Ni, Pb, As and Cd, varied geographically. The measured concentrations of As, Pb and Cr in liquid milk were all lower than the limits of the Chinese standards. According to the result of exposure assessment, the RNIs of Mg, Ca, Se and Mo were higher than 10%. The MOE of Pb was much higher than 1. The PTMI of Cd was lower than 0.1 μg/kg BW/month, and the MOE of Ni was much higher than 10.ConclusionMilk contains abundant nutritious elements and is an important supplementary to human nutrition. In addition, milk generally contains low levels of harmful elements, which poses low risk to human health.

The COVID-19 pandemic caused by SARS-CoV-2 highlighted the importance of reliable detection methods for disease control and surveillance. Optimizing detection antibodies by rational screening antigens would improve the sensitivity and specificity of antibody-based detection methods such as colloidal gold immunochromatography. In this study, we screened three peptide antigens with conserved sequences in the N protein of SARS-CoV-2 using bioinformatical and structural biological analyses. Antibodies that specifically recognize these peptides were prepared. The epitope of the peptide that had the highest binding affinity with its antibody was located on the surface of the N protein, which was favorable for antibody binding. Using the optimal antibody that can recognize this epitope, we developed colloidal gold immunochromatography, which can detect the N protein at 10 pg/mL. Importantly, this antibody could effectively recognize both the natural peptide antigen and mutated peptide antigen in the N protein, showing the feasibility of being applied in the large-scale population testing of SARS-CoV-2. Our study provides a platform with reference significance for the rational screening of detection antibodies with high sensitivity, specificity, and reliability for SARS-CoV-2 and other pathogens. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication. Exos ameliorate immune inflammation levels, alter macrophage phenotypes, regulate mitochondrial metabolic function, and inhibit pulmonary vascular remodeling, thereby improving PH. Macrophages are important sources of cytokines and other transmitters and can promote the release of cytokines, vasoactive molecules, and reactive oxygen species, all of which are associated with pulmonary vascular remodeling. Therefore, the aim of this study was to investigate whether HUCMSC-Exos could improve the lung inflammatory microenvironment and inhibit pulmonary vascular remodeling by targeting macrophages and identifying the underlying mechanisms. The results showed that HUCMSC-Exos promoted M2 macrophage polarization, decreased pro-inflammatory factors, increased IL-10 levels, and inhibited IL-33/ST2 axis expression, thereby inhibiting hypoxia-induced proliferation of pulmonary artery smooth muscle cells and ameliorating HPH. [ABSTRACT FROM AUTHOR]

It is well known that DNA damage can cause apoptosis. However, whether apoptosis and its metabolites contribute to DNA repair is largely unknown. In this study, we found that apoptosis‐deficient Fasmut and Bim−/− mice show significantly elevated DNA damage and premature cellular senescence, along with a significantly reduced number of 16,000 g apoptotic vesicles (apoVs). Intravenous infusion of mesenchymal stromal cell (MSC)‐derived 16,000 g apoVs rescued the DNA damage and premature senescence in Fasmut and Bim−/− mice. Moreover, a sublethal dose of radiation exposure caused more severe DNA damage, reduced survival rate, and loss of body weight in Fasmut mice than in wild‐type mice, which can be recovered by the infusion of MSC‐apoVs. Mechanistically, we showed that apoptosis can assemble multiple nuclear DNA repair enzymes, such as the full‐length PARP1, into 16,000 g apoVs. These DNA repair components are directly transferred by 16,000 g apoVs to recipient cells, leading to the rescue of DNA damage and elimination of senescent cells. Finally, we showed that embryonic stem cell‐derived 16,000 g apoVs have superior DNA repair capacity due to containing a high level of nuclear DNA repair enzymes to rescue lethal dose‐irradiated mice. This study uncovers a previously unknown role of 16,000 g apoVs in safeguarding tissues from DNA damage and demonstrates a strategy for using stem cell‐derived apoVs to ameliorate irradiation‐induced DNA damage. [ABSTRACT FROM AUTHOR]

Brown carbon (BrC) is an important component of biomass-burning (BB) emissions that impacts Earth's radiation budget. BB directly emits primary BrC as well as gaseous phenolic compounds (ArOH), which react in the gas and aqueous phases with oxidants – such as hydroxyl radical (⚫ OH) and organic triplet excited states (3 C ∗) – to form light-absorbing secondary organic aerosol (SOA). These reactions in atmospheric aqueous phases, such as cloud/fog drops and aerosol liquid water (ALW), form aqueous SOA (aqSOA), i.e., low-volatility, high-molecular-weight products. While these are important routes of aqSOA formation, the light absorption and lifetimes of the BrC formed are poorly characterized. To study these aspects, we monitored the formation and loss of light absorption by aqSOA produced by reactions of six highly substituted phenols with ⚫ OH and 3 C ∗. While the parent phenols absorb very little tropospheric sunlight, they are oxidized to aqSOA that can absorb significant amounts of sunlight. The extent of light absorption by the aqSOA depends on both the ArOH precursor and oxidant: more light-absorbing aqSOA is formed from more highly substituted phenols and from triplet reactions rather than ⚫ OH. Under laboratory conditions, extended reaction times in ⚫ OH experiments diminish sunlight absorption by aqSOA on timescales of hours, while extended reaction times in 3 C ∗ experiments reduce light absorption much more slowly. Estimated lifetimes of light-absorbing phenolic aqSOA range from 3 to 17 h in cloud/fog drops, where ⚫ OH is the major sink, and from 0.7 to 8 h in ALW, where triplet excited states are the major sink. [ABSTRACT FROM AUTHOR]

Objective: To investigate the tumor suppressing effect of Shenqi Yiliu decoction combined with cisplatin via ERK-mediated C-Myc/PD-L1 phase-coordinated pathway on H22 hepatocellular carcinoma tumor-bearing mice and its mechanism. Methods: In 60 SPF-grade male Kunming mice, 10 mice were taken as blank group by random number table method, and the other 50 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mouse model. After successful replication of the model, the model mice were randomly divided into model group, cisplatin group [2.5x19-3 g/(kg⋅3 d)], Shenqi Yiliu decoction low [13.515 g/(kg⋅d)], medium [27.03 g/(kg⋅d-1) ], and high dose [27.030 g/(kg⋅d)] combined with cisplatin group [2.5x10-3 g/(kg⋅3 d)], 10 mice in each group were treated for 13 d. After 24 h of the last dose, the mice were anesthetized and sacrificed, and the tumor inhibition rate, spleen index and thymus index of each drug group were determined; HE staining was performed to observe the histopathological changes of tumor in mice; ELISA kit was used to detect the contents of EGF and IFN-γ in tumor tissue homogenate; p-ERKl/2, C-Myc and PD-L1 protein expression in tumor tissue were detected by IHC and Western blot; ERK, C-Myc and PD-L1 mRNA expression levels in tumor tissue were detected by RT-PCR. Results: Compared with blank group, the average body mass and spleen index of mice in model group were decreased (P<0.05). Compared with model group, the tumor inhibition effect of each treatment group was obvious, and Shenqi Yiliu decoction combined with cisplatin group inhibited tumor growth in liver cancer mice in a dose-dependent way, improved the average body mass, spleen index and thymus index of mice, promoted the necrosis of tumor cells and increased the necrotic area. EGF and IFN-γ contents, P-ERK1/2, C-Myc, PD-L1 protein expressions and ERK, C-Myc, PD-L1 mRNA expression levels were decreased in tumor tissues (P<0.05). Compared with cisplatin group, the therapeutic effect of Shenqi decoction combined with cisplatin in medium and high dose groups was significant, and the difference was statistically significant (P<0.05). Conclusion: Shenqi Yiliu decoction combined with cisplatin effectively inhibited the tumor growth of H22 liver cancer tumor-bearing mice and significantly reduces the expression of C-Myc and PD-L1 proteins in the tumor tissues, which may be through the regulation of ERK signaling path-way-related protein expression to exert tumor suppressive effect. [ABSTRACT FROM AUTHOR]

The traditional teaching methods for apexification face difficulties in meeting dental students' practical training needs. Herein, we aimed to find optimal techniques of learning apexification and to evaluate whether a virtual simulation platform for apexification learning was effective. A virtual simulation learning platform for apexification was developed. Ninety-nine 4th-year dentistry students were classified randomly into the control group (Con, receiving conventional teaching) and the experimental group (Exp, receiving virtual simulation teaching). Theoretical tests before (test 1) and after the virtual simulation training (test 2) assessed the effect of learning. In the Exp group, a questionnaire was used to assess student understanding of the virtual simulation platform. In the Exp group, the test-2 scores were significantly better compared those in the Con group (p < 0.001). Furthermore, in the Exp group, the test-2 scores exceeded those of test 1 (p < 0.001). Feedback using the questionnaire covered the evaluation of the Exp group for the virtual reality platform and offered useful suggestions. Applying the virtual simulation learning platform had positive effects on improving learning quality related to apexification. [ABSTRACT FROM AUTHOR]

Recognizing watershed runoff process and its component sources is a prerequisite for the rational use of water resources. To elucidate the effects and quantitative contributions of various vegetation types on the components of watershed runoff, we centered on the Caijiachuan main channel watershed in Jixian, Shanxi and five sub-watersheds with distinct vegetation types. By tracking the hydrological responses to two representative rainfall events and assessing the spatiotemporal variations in hydrogen and oxygen isotope signatures, we aimed to discern disparities in the runoff processes across these sub-watersheds and pinpoint their constituent origins. The results showed that under medium rainfall condition, the contribution rates of event water to the river flow of each watershed were in an order of protected forest (94.3%) > Caijiachuan main channel (83.1%) > agro-pastoral composite (64.3%) > plantation-secondary forest (52.4%) > cropland (0.3%) > secondary forest (0.0%) ; under light rainfall condition, plantation-secondary forest (52.4%) > protected forest (58.5%) > cropland (40.6%) > secondary forest (15.8%) > agro-pastoral composite (12.5%) > Caijiachuan main channel (9.3%). The event water contribution rate of secondary forest and protected forest watersheds to runoff was higher than that of plantation watersheds. The secondary forests watersheds had a stronger runoff storage capacity. The event water contribution rate of protected forest and agro-pastoral composite watersheds under medium rainfall intensity condition was greater than that under light rainfall intensity condition, while the event water contribution rate of cropland, plantation-secondary forest, and secondary forest watersheds was in adverse. The event water contribution to the runoff of forested watersheds was greater than that of cropland watersheds, which may be related to the presence of silt dams at the mouth of agricultural watershed channels. This study can provide a scientific basis for the analysis of water conservation and runoff change attribution in the loess area of west Shanxi. [ABSTRACT FROM AUTHOR]