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Designing atomically monodispersed heterogeneous catalysts with uniform active sites and high atom utilization efficiency is of fundamental and practical interest. Here, the authors report a Pt2/mpg-C3N4 catalyst showing enhanced catalytic performance toward the selective hydrogenation and epoxidation

Abstract Here we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularly deficiency in complex I has previously been associated with the degeneration of dopaminergic neurons in Parkinson’s disease. To further our understanding of the nature of this dysfunction, and to identify Parkinson’s disease specific changes, we validated a panel of antibodies targeting subunits of all five mitochondrial oxidative phosphorylation complexes in dopaminergic neurons from Parkinson’s disease, mitochondrial disease, and control cases. Detailed analysis of the expression profile of these proteins, highlighted heterogeneity between individuals. There is a widespread decrease in expression of all complexes in Parkinson’s neurons, although more severe in mitochondrial disease neurons, however, the combination of affected complexes varies between the two groups. We also provide evidence of a potential neuronal response to mitochondrial dysfunction through a compensatory increase in mitochondrial mass. This study highlights the use of imaging mass cytometry in the assessment and analysis of expression of oxidative phosphorylation proteins, revealing the complexity of deficiencies of these proteins within individual neurons which may contribute to and drive neurodegeneration in Parkinson’s disease.

Abstract Background Most patients with acute myeloid leukemia (AML) remain uncurable and require novel therapeutic methods. Gain-of-function FMS-like tyrosine kinase 3 (FLT3) mutations are present in 30–40% of AML patients and serve as an attractive therapeutic target. In addition, FLT3 is aberrantly expressed on blasts in > 90% of patients with AML, making the FLT3 ligand-based drug conjugate a promising therapeutic strategy for the treatment of patients with AML. Here, E. coli was used as a host to express recombinant human FLT3 ligand (rhFL), which was used as a specific vehicle to deliver cytotoxic drugs to FLT3 + AML cells. Methods Recombinant hFL was expressed and purified from induced recombinant BL21 (DE3) E. coli. Purified rhFL and emtansine (DM1) were conjugated by an N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) linker. We evaluated the potency of the conjugation product FL-DM1 against FLT3-expressing AML cells by examining viability, apoptosis and the cell cycle. The activation of proteins related to the activation of FLT3 signaling and apoptosis pathways was detected by immunoblotting. The selectivity of FL-DM1 was assessed in our unique HCD-57 cell line, which was transformed with the FLT3 internal tandem duplication mutant (FLT3-ITD). Results Soluble rhFL was successfully expressed in the periplasm of recombinant E. coli. The purified rhFL was bioactive in stimulating FLT3 signaling in AML cells, and the drug conjugate FL-DM1 showed activity in cell signaling and internalization. FL-DM1 was effective in inhibiting the survival of FLT3-expressing THP-1 and MV-4-11 AML cells, with half maximal inhibitory concentration (IC50) of 12.9 nM and 1.1 nM. Additionally, FL-DM1 induced caspase-3-dependent apoptosis and arrested the cell cycle at the G2/M phase. Moreover, FL-DM1 selectively targeted HCD-57 cells transformed by FLT3-ITD but not parental HCD-57 cells without FLT3 expression. FL-DM1 can also induce obvious apoptosis in primary FLT3-positive AML cells ex vivo. Conclusions Our data demonstrated that soluble rhFL can be produced in a bioactive form in the periplasm of recombinant E. coli. FL can be used as a specific vehicle to deliver DM1 into FLT3-expressing AML cells. FL-DM1 exhibited cytotoxicity in FLT3-expressing AML cell lines and primary AML cells. FL-DM1 may have potential clinical applications in treating patients with FLT3-positive AML.

One of the focal points in Geographic Information Science (GIS) is to uncover the spatial distribution patterns of geographical phenomena. In response to the insufficient spatial feature learning concerning neighborhoods in traditional machine learning-based Cellular Automata (CA) models for land use change, this study couples the Random Forest (RF) model and the Spatially Non-Stationary Convolutional Neural Network (SNSCNN) model to the CA model. The resulting RF-SNSCNN-CA model considers the issue of spatial non-stationarity by incorporating attention mechanisms. Using observed urban land change data from 2010 to 2017 in the 21 districts of Chongqing’s main city as an example, two sets of experiments comprising eight scenarios were designed to verify the neighborhood effects. The results demonstrate that the proposed RF-SNSCNN-CA model achieves an Overall Accuracy (OA) of 97.82%, Kappa of 0.7683, and Figure of Merit (FoM) of 0.3836. The study reveals the following findings. Firstly, the RF-SNSCNN-CA model integrates the dual advantages of traditional machine learning and deep learning models, in which SNSCNN improves by the combined effect of channel and spatial attention mechanisms improves the learning of neighborhood features; secondly, the machine learning-like urban sprawl CA modeling process, regardless of the approach taken to obtain development suitability, cannot completely replace the learning of the neighborhood part; lastly, the use of traditional neighborhood modeling methods may produce suppression of simulation results and make the model inadequately learn spatial features.

Land use/cover change (LUCC) models are essential for studying the profound impact of land use/cover dynamics on various aspects of the natural and social environment. Cellular Automata (CA) is widely used in the dynamic modeling of complex LUCC systems. In the traditional machine learning CA model, when using statistical methods to obtain neighborhood features, there is usually the problem that the spatio-temporal feature learning of neighborhood factors is insufficient. At the same time, the CA dynamic iteration module using the random seed selection mechanism often has the problem that the seed selection efficiency is very low. In this paper, taking the Chongqing Metropolitan Area as an example, convolutional neural networks (CNN)-Long Short-Term Memory Network (LSTM) is introduced to improve the learning effect of the traditional random forest (RF)-CA model in the spatial and temporal characteristics of neighborhood factors. CNN is used to extract the spatial dimension features of LUCC in the neighborhood, and the LSTM model is used to extract the time dimension features and long-term dependencies. At the same time, a high-quality seed selection iterative algorithm (HQSSIA) is used to improve the accuracy of the multi-land-use dynamic change model and the efficiency of the iterative algorithm. The results show that, the proposed model performs better than other models in simulating the LUCC from 2015 to 2020 (Kappa = 0.9684, FOM = 0.1744, Accuracy = 0.9829, F1 = 0.9641, Hamming = 0.0171) and from 2010 to 2020 (Kappa = 0.9599, FOM = 0.4662, Accuracy = 0.9785, F1 = 0.8113, Hamming = 0.0214). After introducing the CNN-LSTM model, the Figure of Merit (FOM) increased by 1.56% and 18.88% for 2015–2020 and 2010–2020. Compared with the CA model-based random seed selection algorithm, the FOM of the model using HQSSIA in the dynamic iteration module are improved by 11.60% and 24.79% for 2015–2020 and 2010–2020, and the operation efficiency of the dynamic iteration module is improved by about 19 times. Compared with the current mainstream LUCC models PLUS and FLUS, the proposed model has improved 14.38%, 37.55%, and 14.93%, 37.74% in FOM, respectively, for 2015–2020 and 2010–2020. The research shows that: (1) RF-CNN-LSTM-CA model not only retains the interpretability advantage of the traditional RF-CA model, but also improves the accuracy of the whole model by improving the spatio-temporal characteristics of neighborhood factors through in-depth learning; (2) the HQSSIA can quickly and accurately search for cells to be converted with higher conversion probability in the observed data, which can not only significantly reduce the time complexity of the model, but also improve the accuracy of LUCC simulation.

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed via the gastrointestinal tract and formed via biotransformation in human, respectively. Together with data from screening by comprehensive 2D angiotensin-converting enzyme 2 (ACE2) biochromatography, 8 components in LHQW that were exposed to human and had potential ACE2 targeting ability were identified for further pharmacodynamic evaluation. Results show that rhein, forsythoside A, forsythoside I, neochlorogenic acid and its isomers exhibited high inhibitory effect on ACE2. For the first time, this study provides chemical and biochemical evidence for exploring molecular mechanisms of therapeutic effects of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to human. It also demonstrates the utility of the human exposure-based approach to identify pharmaceutically active components in Chinese herb medicines.

In the reconstruction of cylindrical phase-only hologram (POH), speckle noise caused by the addition of random phase is rarely discussed. Although some speckle noise suppression algorithms have been proposed for planar POH, it does not work well if they are directly applied to cylindrical POH. To solve this issue, the cylindrical self-diffraction iteration (CSDI) algorithm is proposed. This is an iteration algorithm based on the cylindrical self-diffraction model which is a special case of the cylindrical backward-propagation model at a limit condition. Simulation results show that CSDI can suppress speckle noise and improve the quality of reconstructed images significantly. Furthermore, the proposed CSDI algorithm outperforms conventional algorithms, which work well in planar POH and are directly applied to cylindrical POH, in suppressing speckle noise for cylindrical POH. To our best knowledge, the models of cylindrical backward-propagation and cylindrical self-diffraction as well as the concept of CSDI are firstly proposed and applied to speckle suppression of cylindrical POH.

It is economic and secure to determine the optimal siting and sizing of the offshore wind farms (OWFs) integrated into the AC system through voltage-source converter high-voltage direct current (VSC-HVDC) links. In this paper, an integrated planning model for the VSC-HVDC-link-based OWFs and the capacitors is proposed, where a decomposition technique is presented to solve the proposed mixed-integer nonlinear programming (MINLP) problem and obtain the optimal solution. This model can optimize the siting and sizing of the OWFs to improve the voltage profile and reduce the adverse influence of the reactive power of the OWFs. With the proposed planning model, the total investment costs, operation costs and maintenance costs of the OWFs, VSC-HVDC links, and the capacitors can be minimized. Simulations on the modified IEEE 118-bus system show that the proposed integrated planning model can provide more economic scheme than the independent planning scheme, in which the capacitors are planned after the OWFs. Besides, a series of sensitivity analysis on certain equipment costs are studied to obtain the regular pattern for sizing VSC stations.

In order to optimize the existing signal control period division method and improve signal control effect, a new period division method based on Locally Linear Embedding and Particle Swarm Optimization combined with K-means clustering (LLE-PSO-K) algorithm is proposed in this paper. Firstly, traffic flow characteristics of signal-controlled intersections are fully considered, and a multi-dimensional flow matrix is constructed based on the phase traffic flow. In order to reduce the computational complexity of the model and improve the operating efficiency of the method, manifold learning Locally Linear Embedding (LLE) algorithm is brought in to reduce the dimension of the multidimensional phase flow matrix. Then, the dimensionality reduction matrix is used as input data, and signal control period is divided by using Particle Swarm Optimization combined with K-means clustering (PSO-K) algorithm. Finally, an actual intersection in a city is selected to verify the performance of the proposed method. For comparative analysis, control periods are divided based on the phase traffic flow data with 15min, 30min and 1h interval respectively. Results show that for different time intervals, the division of the proposed method is better than other methods, of which the invalid control periods are less. Besides, the optimal clustering number can be obtained, which proves the effectiveness of the new proposed method.

Background and ObjectiveIt is urgent to find out an alternative therapy for Kawasaki disease (KD) since around 20% patients are resistant to intravenous immunoglobulin (IVIG) or aspirin. Tanshinone IIA is the active component of the traditional Chinese medicine Danshen (Salvia miltiorrhiza), which has anti-inflammatory and anti-platelet properties; however, whether or not tanshinone IIA has a therapeutic effect on KD remains unclear. Therefore, the present study aimed to examine the effect of tanshinone IIA on KD patients and rabbits with immune vasculitis, and to identify the potential mechanisms with special emphasis on megakaryopoiesis and megakaryocytic apoptosis.MethodsKawasaki disease patients were recruited and prescribed with tanshinone IIA in the absence or presence of aspirin and IVIG, and the inflammatory responses and platelet functions were determined. Megakaryocytes (MKs) isolated from rabbits with immune vasculitis and human megakaryocytic CHRF-288-11 cells were treated with tanshinone IIA to examine the colony forming unit (CFU) and apoptosis, respectively. Microarray assay was conducted to identify potential targets of tanshinone IIA-induced apoptosis.ResultsTanshinone IIA reduced the serum levels of C-reactive protein (CRP), interleukin (IL)-1β, IL-6, and P-selectin in KD patients; such inhibitory effect was more significant compared to aspirin and IVIG. It also dose-dependently lowered the levels of tumor necrosis factor (TNF)-α and IL-8 in peripheral blood mononuclear cells isolated from KD patients. In rabbits with immune vasculitis, tanshinone IIA significantly reduced the serum levels of proinflammatory cytokines and platelet functions. In addition, tanshinone IIA significantly decreased the number of bone marrow MKs and inhibited the Colony Forming Unit-Megakaryocyte (CFU-MK) formation. In human megakaryocytic CHRF-288-11 cells, tanshinone IIA induced caspase-dependent apoptosis, probably through up-regulating TNF receptor superfamily member 9 (TNFRSF9) and the receptor (TNFRSF)-interacting serine/threonine-protein kinase 1 (RIPK1), which may contribute to its anti-platelet and anti-inflammatory properties.ConclusionTanshinone IIA exerts better anti-inflammatory and anti-platelet effects in treating KD patients than aspirin and IVIG. It attenuates immune vasculitis likely by inhibiting IL-mediated megakaryopoiesis and inducing TNFRSF9/RIPK1/caspase-dependent megakaryocytic apoptosis. The findings therefore suggest that tanshinone IIA may be a promising alternative therapy for the treatment of KD.

Previous studies evaluated the adenosine receptor antagonists alone to determine their effects on oxidative stress, but little is known about adenosine’s protective efficacy when oxidative injury occurs in vivo. Adenosine is a crucial signaling molecule recognized by four distinct G-protein-coupled receptors (GPCRs) (i.e., A1R, A2AR, A2BR, and A3R) and protects cells against pathological conditions. The present study was performed to evaluate the role of antagonist modulation in the setting of paraquat toxicity with adenosine pretreatment. First, PC12 cells were exposed to paraquat (850 μM) and adenosine (30 μM) to develop an in vitro model for the antagonist effect assay. Second, we found that the A1R antagonist DPCPX enhanced the viability of paraquat-induced PC12 cells that underwent adenosine pretreatment. Moreover, the A2AR antagonist ZM241385 decreased the viability of paraquat-induced PC12 cells that underwent adenosine pretreatment. Our findings indicate that adenosine protection requires a dual blockade of A1R and activation of A2AR to work at its full potential, and the A2B and A3 adenosine receptor antagonists increased paraquat-induced oxidative damage. This represents a novel pharmacological strategy based on A1/A2A interactions and can assist in clarifying the role played by AR antagonists in the treatment of neurodegenerative diseases.

Objective: Metabolic acidosis often occurs in the paediatric intensive care unit (PICU). Although sodium bicarbonate (SB) has been widely used in paediatrics, data on the effect of SB on children with metabolic acidosis in the PICU are scarce.Methods: Patients with metabolic acidosis who were treated with SB within 48 h of PICU admission were screened. Multivariate logistic regression, subgroup analysis, and propensity score matching (PSM) were used to investigate the relationships between SB infusion and clinical outcomes.Results: A total of 1,595 patients with metabolic acidosis were enrolled in this study. In the multivariate logistic regression model, SB infusion was not correlated with in-hospital mortality (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.47–1.63, p = 0.668), but was significantly correlated with hypernatraemia (OR 1.98, 95% CI 1.14–3.46, p = 0.016), hypokalaemia (OR 2.01, 95% CI 1.36–2.96, p < 0.001), and hypocalcaemia (OR 4.29, 95% CI 2.92–6.31, p < 0.001). In the pH value, lactate level, acute kidney injury level, age grouping, and anion gap level subgroups, the ORs for SB and in-hospital mortality were not statistically significant. After PSM, the results remained unchanged.Conclusion: SB infusion does not reduce the in-hospital mortality of severely ill children with metabolic acidosis and increases the risk of hypernatraemia, hypokalaemia, and hypocalcaemia. More effort should be focused on eliminating the causes of metabolic acidosis rather than SB infusion.

Heat stress has been considered as a critical risk factor for decreasing performance and causing oxidative stress in broilers. The tryptophan (TRP) derivative 5-hydroxytryptophan has been reported to protect membrane fluidity in broilers suffering from oxidative stress. Therefore, this experiment was conducted to investigate the effects of dietary TRP supplementation on antioxidant status and mitochondrial function-related genes expressions in broilers exposed to acute heat stress (34 ± 1°C, 24 h). Female Arbor Acres broilers (19-d-old, n = 180) were randomly assigned to 1 of 3 treatments. Broilers were fed a basal diet and in the thermoneutral conditions (TN, 23 ± 1°C) was considered as the TN group. Broilers were fed a basal diet and exposed to acute heat stress (HS, 34 ± 1°C) was regarded as the HS group. Broilers were fed a basal diet supplemented with 0.18% L-tryptophan and under HS conditions was treated as the HS + TRP groups. Heat stress led to increased malondialdehyde (MDA) concentration (P < 0.05), while it elevated catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity activities (T-AOC) (P < 0.05) compared with the TN group. Nevertheless, compared with the HS group, TRP supplementation increased SOD activity (P < 0.05). The effects of acute heat stress were associated with increased mRNA abundance for redox-related genes (P < 0.05), and reduced mRNA levels for mitochondrial function-related genes (P < 0.05). Notably, the effects of acute heat stress on mitochondrial function-related genes expressions were reversed by TRP treatment. Collectively, dietary 0.18% TRP supplementation beneficially protects against acute heat stress-induced oxidation stress and mitochondrial dysfunction by regulating antioxidant states and increasing mitochondrial function-related genes expressions in broilers.

Abstract Background A secondary malignancy is the most serious complication in lung cancer (LC) survivors. This study aimed to evaluate the clinicopathological features, predictable risk factors and survival of patients with LC who developed therapy-related acute myeloid leukaemia (t-AML). Methods Patients from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with t-AML after LC between 1975 and 2015 were included. Standardized incidence ratios (SIRs) were used to perform multiple primary analyses. The risk of t-AML development among LC patients was assessed using a logistic regression model. Kaplan–Meier analysis was used to construct overall survival (OS) curves. Cox regression was used to assess the influence of various prognostic factors. Results A total of 104 patients with t-AML after LC-targeting chemotherapy were included. The median latency period to the development of t-AML was 35.5 months. The calculated SIR of t-AML was 4.00. Chemoradiotherapy, small cell lung cancer (SCLC), or localized/regional-stage LC was a risk factor for the development of t-AML. The median OS was only 1 month, and those younger than 65 years were predicted to have a better OS time. Conclusions t-AML is a rare but serious late complication in LC patients and is associated with a poor prognosis. It is necessary to carry out long-term follow-up and screen for t-AML in LC patients, especially among those undergoing both radiotherapy and chemotherapy, with SCLC or with localized/regional-stage LC.

Abstract Background The association of myocardial bridge (MB) with cardiovascular risk and the possible cardiovascular risk factors remain unclear. This study aimed to explore the clinical characteristics and related factors of coronary stenosis proximal to an MB. Methods This was a retrospective study of patients with symptoms of coronary atherosclerotic heart disease admitted between 10/2011 and 12/2014 to the Emergency and Cardiology Department of Bayannur Hospital, who underwent selective coronary angiography (SCAG). The patients were assigned to the non-stenosis and stenosis groups according to whether coronary stenosis was proximal to the MB. Results Among 244 patients with MB and cardiovascular symptoms, 91 (37.3%) had stenosis proximal to the MB. Compared with the non-stenosis group, there were more males (80.2% vs. 55.6%, P

Abstract Background Epithelial ovarian cancer (EOC) is a highly lethal malignancy. Improvement in genetic characterization of EOC patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments. One of the most relevant cancer-specific actionable targets are protein tyrosine kinases (PTKs) whose role in EOC need to be better investigated. Methods EOC genomic datasets are retrieved and analyzed. The biological and clinical significance of RET genomic aberrations in ovarian cancer context are investigated by a series of in vitro and in vivo experiments. Results Epithelial ovarian cancer sequencing projects identify recurrent genomic RET missense mutations in 1.98% of patients, ranking as the top-five hit among the 100 receptor tyrosine kinases-encoding genes. RET mutants R693H and A750T show oncogenic transformation properties in NIH3T3 cells. Introduction of the RET mutants into human EOC cells increases RET signaling, cell viability, anchorage-independent cell growth and tumor xenograft growth in nude mice, demonstrating that they are activating mutations. RET mutants significantly enhance the activation of RET and its downstream MAPK and AKT signaling pathway in ovarian cancer cells. Vandetanib, a clinical approved RET inhibitor, inhibits the cell viability and decreases the activation of RET-MAPK signaling pathways in EOC cells expressing oncogenic RET mutants. Conclusions The discovery of RET pathogenic variants in the EOC patients, suggests a previously underestimated role for RET in EOC tumorigenesis. The identification of the gain-of-function RET mutations in EOC highlights the potential use of RET in targeted therapy to treat ovarian cancer patients.

Abstract Background A large number of students at a school in Guangzhou city developed a sudden onset of symptoms of diarrhea and vomiting. To help control the outbreak, we conducted an epidemiological investigation to determine the causative agent, sources, role of transmission and risk factors of the infections. Methods The study population consisted of probable and confirmed cases. An active search was conducted for cases among all students, teachers and other school staff members. A case control study was carried out using standardized online questionnaires. Data were obtained regarding demographic characteristics, gastrointestinal symptoms, personal hygiene habits, history of contact with a person who had diarrhea and/or vomiting and dining locations during the past 3 days. Rectal swabs or stool samples of the cases and, food handlers, as well as environmental samples were collected to detect potential intestinal viruses and bacteria. We calculated odds ratios and 95% confidence intervals (CIs). Results A total of 157 individuals fit the definition of a probable case, including 46 with laboratory-confirmed norovirus infection between March 8 and March 22, 2018. The proportion of students who had eaten delivery food 3 days before the onset of illness in the case group was 2.69 times that in the control group (95%CI: 1.88–3.85). Intake of take-out food 3 days earlier, and exposure to similar cases 72 h before onset and case in the same dormitory were risk factors. A total of 20 rectal swab samples from students, 10 rectal swabs from food handlers and 2 environmental swab samples from the out-campus restauranttested positive for norovirus (GII, genogroup II strain). Conclusions We investigated an outbreak of norovirus infectious diarrhea. Food handling practices carry potential risk of acute gastroenteritis outbreaks owing to a lack of surveillance and supervision. Greater attention should be paid to the monitoring and supervision of food handlers in off campus restaurant to reduce the incidence of norovirus-related acute gastroenteritis associated with delivery food.

The double phase method is an efficient way to generate phase-only holograms with high reconstruction quality due to no addition of a random phase. However, it cannot directly encode the Fourier spectrum because of the limited gray modulation range of spatial light modulator, and quantization error. This shortage restricts the application of the double phase in the phase-only Fourier hologram, and this issue is never discussed, and solved as far as we know. To solve this issue, we propose a method to generate phase-only Fourier hologram by analyzing quantization error, and adding a proper quadratic phase. The proposed method overcomes the shortage, and outperforms the non-iterative bidirectional error diffusion method in reconstruction quality, and calculation speed with 8.9 dB higher, and 33 times faster on average, respectively.

The novel curcumin analog C086, previously identified as an oral novel heat shock protein 90 (Hsp90) inhibitor, was found to exhibit anti-hepatoma activity in vitro and in vivo. However, owing to its limited aqueous solubility, the usage of C086 in the clinical application was restricted. This research focused on the increase of the aqueous solubility and bioavailability of C086 via a solid dispersion preparation to improve its accumulation in the liver, which accordingly enhanced anti-hepatoma activity. C086-solid dispersion (C086-SD) was successfully prepared by using solvent evaporation technology. As compared with bulk compound, aqueous solubility obtained with the optimal formulation (C086/PVP k30:1/6 (w/w)) was increased by 1.741 million-fold, and in the following oral administration experiment, bioavailability was found to be improved by an approximately 28-fold relative to C086-Suspension and accumulate preferably in the liver. Accordingly, C086-SD exhibited stronger potent anti-proliferative effects against liver cancer cell line (i.e. HepG2) than pure C086. Moreover, C086-SD was found to have an enhanced anti-hepatoma effect using the orthotopic hepatocellular carcinoma xenograft in BALB/C nude mice. The results above suggested the potential application of C086-SD in the treatment of liver cancer.

Purpose This study was conducted to prepare a novel tumor-biotargeting high-intensity focused ultrasound (HIFU) synergist for indirectly delivering lipid nanoparticles based on the targeting ability of Bifidobacterium longum to the hypoxic region of solid tumors. The effects of two different delivery methods on the imaging and treatment of solid tumors enhanced by lipid nanoparticles were compared. Methods Biotinylated lipid nanoparticles coated with PFH were prepared, cross-linked with B. longum in vitro using a streptavidin-conjugated B. longum antibody (SBA), and observed and detected by laser confocal microscopy and flow cytometry. Solid tumors were treated with HIFU and PFH/BL-NPs. The effects of different delivery methods on the tumor targeting and efficiency of retention of PFH/BL-NPs were observed using Small animal live imaging and frozen sections from small animals. Results The PFH/BL-NPs prepared in this study showed good biocompatibility and safety. PFH/BL-NPs and B. longum were cross-linked in a cluster-like manner (confocal laser scanning microscope) in vitro, with a cross-linking rate of 84 ± 6.23% (flow cytometry). The delivery of B. longum followed by that of PFH/BL-NPs not only enhanced the ability of PFH/BL-NPs to target solid tumors (small animal live imaging), but also increased the retention time of PFH/BL-NPs in the tumor (frozen slices), enhancing the effect of the HIFU synergist. Conclusion Delivery of B. longum followed by that of PFH/BL-NPs can enhance the imaging of solid tumors and effectively improve the efficiency of HIFU treatment of solid tumors, providing a basis for further clinical work.

The coronavirus disease 2019 (COVID-19) pandemic has fueled anti-Asian, especially anti-Chinese sentiments worldwide, which may negatively impact diasporic Chinese youths’ adjustment and prosocial development. This study examined the association between compassion, discrimination and prosocial behaviors in diasporic Chinese youths during the COVID-19 pandemic. 360 participants participated and completed the multi-country, cross-sectional, web-based survey between April 22 and May 9, 2020, the escalating stage of the pandemic. This study found compassion as prosocial behaviors’ proximal predictor, while discrimination independently predicted participation in volunteering, and could potentially enhance the association between compassion and charitable giving. These findings suggest that prosociality among young people is sensitive to social context, and that racial discrimination should be considered in future prosocial studies involving young members of ethnic and racial minorities.

Objective. The current study aimed to compare the characteristics of chromosome abnormalities detected by conventional G-banding karyotyping, chromosome microarray analysis (CMA), or fluorescence in situ hybridization (FISH)/CNVplex analysis and further explore the application value of combined karyotype analysis and CMA in prenatal diagnosis with a larger sample size. Methods. From March 2019 to March 2021, 3710 amniocentesis samples were retrospectively collected from women who accepted prenatal diagnosis at 16 to 22 + 6 weeks of pregnancy. The pregnant women underwent karyotype analysis and CMA. In the case of fetal chromosomal mosaicism, FISH or CNVplex analysis was utilized for validation. Results. In total, 3710 G-banding karyotype results and CMA results from invasive prenatal diagnosis were collected. Of these, 201 (5.41%) fetuses with an abnormal karyotype were observed. The CMA analysis showed that the abnormality rate was 9.14% (340/3710). The detection rate of CMA combined with karyotype analysis was 0.35% higher than that of CMA alone and 4.08% higher than that of karyotyping alone. Additionally, 12 cases had abnormal karyotype analysis, despite normal CMA results. To further detect the chromosome mosaicism, we used FISH analysis to correct the karyotype results of case 1. Correspondingly, a total of 157 cases showed abnormal CMA results but normal karyotype analysis. We also found chromosomal mosaicism in 4 cases using CMA. Moreover, CNVplex and CMA demonstrated that representative case 15 was mosaicism for trisomy 2. Conclusions. Conventional G-banding karyotyping and CMA have their own advantages and limitations. A combination of karyotype analysis and CMA can increase the detection rate of chromosome abnormalities and make up for the limitation of signal detection.

To explore the association of the biochemical markers after birth with BPD-PAH, factors independently predicting BPD-PAH risk were identified by multivariate logistic regression. Cut off values were determined by plotting receiver-operator curve (ROC), for the sake of dichotomizing continuous variables that showed independent relation with BPD-PAH risk. The results show that uric acid (UC) and blood urea nitrogen (BUN) contents markedly increased among infants experiencing BPD-PAH in comparison with those without BPD-PAH (11.6 vs. 9.7 mmol/L, P=0.006 and 482.0 vs. 249.0 μmol/L, P

Coronavirus disease 2019 (COVID-19) remains a global pandemic. Early warning scores (EWS) are used to identify potential clinical deterioration, and this study evaluated the ability of the Rapid Emergency Medicine score (REMS), National Early Warning Score (NEWS), and Modified EWS (MEWS) to predict in-hospital mortality in COVID-19 patients. This study retrospectively analyzed data from COVID-19 patients who presented to the emergency department and were hospitalized between 1 May and 31 July 2021. The area under curve (AUC) was calculated to compare predictive performance of the three EWS. Data from 306 COVID-19 patients (61 ± 15 years, 53% male) were included for analysis. REMS had the highest AUC for in-hospital mortality (AUC: 0.773, 95% CI: 0.69–0.85), followed by NEWS (AUC: 0.730, 95% CI: 0.64–0.82) and MEWS (AUC: 0.695, 95% CI: 0.60–0.79). The optimal cut-off value for REMS was 6.5 (sensitivity: 71.4%; specificity: 76.3%), with positive and negative predictive values of 27.9% and 95.4%, respectively. Computing REMS for COVID-19 patients who present to the emergency department can help identify those at risk of in-hospital mortality and facilitate early intervention, which can lead to better patient outcomes.

Natural environmental factors and human activity intensity factors, the two main factors that affect the spatial and temporal distribution of PM2.5 concentration near the surface, have different mechanisms of action on PM2.5 concentration. In this paper, a GTWR-XGBoost two-stage sequential hybrid model is proposed aiming at detecting the expression of spatiotemporal heterogeneity in the traditional machine learning retrieval model of PM2.5 concentration and the difficulty of expressing the complex nonlinear relationship in the statistical regression model. In the first stage, the natural environmental factors are used to predict PM2.5 concentration with spatiotemporal characteristics by collinearity diagnosis method and Geographically and Temporally Weighted Regression method (GTWR). In the second stage, the simulation results in the first stage and the natural factors eliminated through LUR stepwise regression in the first stage are into the XGBoost model together with the human activity intensity factors in the buffer zone with the best correlation coefficient of PM2.5, and finally the temporal and spatial distribution of PM2.5 concentration. Taking the Chengdu Chongqing Economic Circle as an example, the proposed model is used to retrieve PM2.5 concentration and compared with the single GTWR, XGBoost, and coupling model published recently. The experimental results show that the R2, RMSE, and MAE of the GTWR-XGBoost two-stage model cross-validation are 0.92, 5.44 ug·m−3, and 4.12 ug·m−3, respectively. Compared with the above single models, R2 increased by 0.01 and 0.12, and MAE decreased by more than 0.11 and 3.1, respectively. Compared with the coupling model published recently, R2 is increased by 0.02, and MAE is reduced by more than 0.4. In addition, the PM2.5 concentration in Chengdu Chongqing showed obvious seasonal temporal and spatial changes, and the influence ratios of natural environmental factors and human activity intensity activities factors on PM2.5 were 0.66 and 0.34. The results show that the GTWR-XGBoost two-stage Model can not only describe the heterogeneity and objectively reflect the complex nonlinear relationship between the phenomenon and the influencing factors, but also enhance the interpretability of the phenomenon when simulating the spatiotemporal distribution characteristics of PM2.5 concentration.

To understand the pollution characteristics of volatile organic compounds (VOCs) in the glass deep-processing industry, samples were collected using polyvinyl fluoride bags and quickly transferred to summa tanks for GC/MS/FID analysis. The emission characteristics of VOCs, the ozone formation potential and the secondary aerosol formation potential were studied. The results showed that the VOCs emitted by the six enterprises were mainly aromatics and OVOCs, accounting for 35% to 97% of the emissions, with high emission loads of alkanes and halocarbons from individual enterprises. The stack emissions from Enterprise 2 were as high as 38 mg/m3, while the emissions from the remaining five enterprises were all in the range of 1.7~4.1 mg/m3, probably because the terminal treatment facilities were not updated in a timely manner, resulting in excessive stack emissions from Enterprise 2. The characteristic pollutants, including OVOCs, aromatics and alkanes, which are mainly derived from spray painting and gluing, were screened in the six enterprises. Aromatics and OVOCs contributed the most to the ozone formation potential in the six enterprises, with some enterprises having a high contribution from alkanes and alkenes. On the basis of the secondary aerosol formation potential, toluene, benzene, ethylbenzene, o-xylene and m/p-xylene account for 98% of the six enterprises’ emissions. Glass enterprises should prioritise the control of benzene and OVOCs emissions. The glass processing industry mainly emits aromatics, OVOCs and alkanes. Through a preliminary study on the emission characteristics of VOCs in the glass deep-processing industry, we provided basic data for the reduction and control of VOCs in the glass deep-processing industry in China.

Loosened rock circle is formed around the tunnel when the tunnel is constructed by the drilling and blasting method. The size of the loosened rock circle around the tunnel and the degree of internal rock fragmentation has an important influence on the support parameters, durability, and safety of the tunnel. Firstly, referencing an existing tunnel project, blasting tests using nonelectronic and electronic detonators were carried out to determine the influence of blasting construction on the scope of the rock loose circle and the degree of rock fragmentation. Then, a numerical simulation was used to study the contribution of the blasting impact and surrounding rock stress redistribution on the loosened rock circle around the tunnel. The results showed that the range of the loosened rock circle around the tunnel generated by the normal blasting of nonelectronic detonators was 1.5~2.3 m, and the wave velocity of the rock mass in the loosened rock circle around the tunnel decreased to 23~36%. The size of the loosened rock circle around the tunnel generated by the blasting impact was 0.66 m, accounting for 33% of the range of the loosened rock circle around the tunnel. The range of the loosened rock circle around the tunnel produced by electronic detonator blasting was 0~1.4 m. The wave velocity of the rock mass in the loosened rock circle around the tunnel decreased to 12~17%. The range of the loosened rock circle around the tunnel was approximately 60~76% of that of detonator blasting, and the broken degree of the surrounding rock in the loosened rock circle around the tunnel was small. The research results can provide a reference for the optimization design of preliminary support parameters of tunnels, such as anchors and steel arches in blasting construction.

Abstract. Background:. Tuberculosis (TB) is one of the most debilitating diseases worldwide. Current studies have shown that vitamin D plays a significant role in host immune defense against Mycobacterium tuberculosis, but clinical trials reported inconsistent results. Therefore, we systematically reviewed the literature to investigate whether vitamin D supplementation could improve the effect of anti-TB therapy. Methods:. We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from their inception to February 8th, 2019 for randomized controlled trials on vitamin D supplementation in patients with pulmonary TB receiving anti-TB therapy. The primary outcomes were time to sputum culture and smear conversion and proportion of participants with negative sputum culture. The secondary outcomes were clinical response to treatment and adverse events. A random-effects model was used to pool studies. Data were analyzed using RevMan 5.3 software. Results:. Five studies with a total of 1126 participants were included in our meta-analysis. Vitamin D supplementation did not shorten the time to sputum culture and smear conversion (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.89–1.23, P = 0.60; HR 1.15, 95% CI 0.93–1.41, P = 0.20, respectively) and did not lead to an increase in the proportion of participants with negative sputum culture (relative risk [RR] 1.04, 95% CI 0.97–1.11, P = 0.32). However, it reduced the time to sputum culture conversion in the sub-group of participants with TaqI tt genotype (HR 8.09, 95% CI 1.39–47.09, P = 0.02) and improved the multidrug-resistant (MDR) TB sputum culture conversion rate (RR 2.40, 95% CI 1.11–5.18, P = 0.03). There was no influence on secondary outcomes. Conclusions:. Vitamin D supplementation had no beneficial effect on anti-TB treatment, but it reduced the time to sputum culture conversion in participants with tt genotype of the TaqI vitamin D receptor gene polymorphism and improved the MDR TB sputum culture conversion rate.

Alternative end joining (A-EJ) catalyzes substantial level of antibody class switch recombination (CSR) in B cells deficient for classical non-homologous end joining, featuring increased switch (S) region DSB resection and junctional microhomology (MH). While resection has been suggested to initiate A-EJ in model DSB repair systems using engineered endonucleases, the contribution of resection factors to A-EJ-mediated CSR remains unclear. In this study, we systematically dissected the requirement for individual DSB resection factors in A-EJ-mediated class switching with a cell-based assay system and high-throughput sequencing. We show that while CtIP and Mre11 both are mildly required for CSR in WT cells, they play more critical roles in mediating A-EJ CSR, which depend on the exonuclease activity of Mre11. While DNA2 and the helicase/HRDC domain of BLM are required for A-EJ by mediating long S region DSB resection, in contrast, Exo1’s resection-related function does not play any obvious roles for class switching in either c-NHEJ or A-EJ cells, or mediated in an AID-independent manner by joining of Cas9 breaks. Furthermore, ATM and its kinase activity functions at least in part independent of CtIP/Mre11 to mediate A-EJ switching in Lig4-deficient cells. In stark contrast to Lig4 deficiency, 53BP1-deficient cells do not depend on ATM/Mre11/CtIP for residual joining. We discuss the roles for each resection factor in A-EJ-mediated CSR and suggest that the extent of requirements for resection is context dependent.

This study aimed to explore the effect of programmed death-ligand 1 (PD-L1) in cancer-associated fibroblasts (CAFs) on advanced laryngeal squamous cell carcinoma (LSCC). The expression of PD-L1 in advanced LSCC tumor tissues was observed in 83 patients with LSCC by immunofluorescence microscopy and compared with that in normal laryngeal mucosa. The CAFs of LSCC and normal fibroblasts (NFs) were isolated, cultured, purified, and examined by fluorescence. The expression of PD-L1 in purified CAFs and NFs was measured by flow cytometry. The expression of PD-L1 in CAFs was downregulated through small interferring RNA (siRNA) transfection. The proliferation and migration capacities of CAFs were observed using proliferation and scratch tests, respectively. The proliferation of HEP-2 cells and T cells was measured after cocultured with CAFs. The secretion of interleukins IL-2 and IL-10 was detected using enzyme-linked immuno sorbent assay (ELISA). PD-L1 was expressed in 62 of 83 cases of the advanced LSCC tumor tissues. Also, CAFs expressed more PD-L1 compared with NFs. The proliferation and migration capacities of CAFs were significantly lower after transfection with PD-L1-siRNA. The proliferation rate of HEP-2 cells cocultured with CAFs decreased in PD-L1-siRNA-transfected cells. However, the proliferation rate of T cells increased in transfected cells. The ELISA results showed that the secretion of IL-2 increased and that of IL-10 decreased in PD-L1-siRNA-transfected cells. The expression of PD-L1 in CAFs of advanced LSCC was higher than that in NFs. The downregulation of PD-L1 reduced the proliferation and migration of CAFs and HEP-2 cells but enhanced the proliferation and pro-inflammatory function of T cells in the coculture experiment.

The intending island service restoration method is one of the core technologies of self-healing control for smart distribution systems, which aims to maximize the restoration of the out-of-service loads in the out-of-service area without faults quickly. For this reason, a topology-weighted directional traversal intending island recovery method considering the uncertainty of distributed generation sources is proposed. First, divide the network level of the power-loss feeder and calculate the interval power flow of the feeder before the fault, and obtain the power flow direction when the active and reactive power of the faulted branch is the smallest so as to determine whether the distributed generation supply in the non-faulty power-loss area can restore all load power supply. If not, to determine the island recovery plan, continue to compare the distributed generation supply and the load capacity at all levels, and give priority to recovering loads with higher importance levels and smaller network levels. The traversal of the topological authority and direction effectively reduces the island recovery time and can make full use of the distributed generation output to maximize the recovery of the non-faulty power-loss area. Taking the PG&E 69-node system as an example and using the BFGS trust region algorithm to calculate the island power flow without unbalanced nodes for verification, the results show that this method consumes less time and can restore more load power supply than the existing island recovery method, which verifies the method’s effectiveness and reasonability.

Abstract The unbound concentrations of 14 commercial drugs, including five non‐efflux/uptake transporter substrates—Class I, five efflux transporter substrates—class II and four influx transporter substrates—Class III, were simultaneously measured in rat liver, muscle, and blood via microanalysis. Kpuu,liver and Kpuu,muscle were calculated to evaluate the membrane transport activity and cell metabolism on the unbound drug concentrations in the skeletal muscle and liver. For Class I compounds, represented by antipyrine, unbound concentrations among liver, muscle and blood are symmetrically distributed when compound hepatic clearance is low. And when compound hepatic clearance is high, unbound concentrations among liver, muscle and blood are asymmetrically distributed, such as Propranolol. For Class II and III compounds, overall, the unbound concentrations among liver, muscle, and blood are asymmetrically distributed due to a combination of hepatic metabolism and efflux and/or influx transporter activity.

Objective: Identifying high-risk children with a poor prognosis in pediatric intensive care units (PICUs) is critical. The aim of this study was to assess the predictive value of early plasma osmolality levels in determining the clinical outcomes of children in PICUs.Methods: We retrospectively assessed critically ill children in a pediatric intensive care database. The locally weighted-regression scatter-plot smoothing (LOWESS) method was used to explore the approximate relationship between plasma osmolality and in-hospital mortality. Linear spline functions and stepwise expansion models were applied in conjunction with a multivariate logistic regression to further analyze this relationship. A subgroup analysis by age and complications was performed.Results: In total, 5,620 pediatric patients were included in this study. An approximately “U”-shaped relationship between plasma osmolality and mortality was detected using LOWESS. In the logistic regression model using a linear spline function, plasma osmolality ≥ 290 mmol/L was significantly associated with in-hospital mortality [odds ratio (OR) 1.020, 95% confidence interval (CI) 1.010–1.031], while plasma osmolality

Summary: Robust alternative end joining (A-EJ) in classical non-homologous end joining (c-NHEJ)-deficient murine cells features double-strand break (DSB) end resection and microhomology (MH) usage and promotes chromosomal translocation. The activities responsible for removing 3′ single-strand overhangs following resection and MH annealing in A-EJ remain unclear. We show that, during class switch recombination (CSR) in mature mouse B cells, the structure-specific endonuclease complex XPF-ERCC1SLX4, although not required for normal CSR, represents a nucleotide-excision-repair-independent 3′ flap removal activity for A-EJ-mediated CSR. B cells deficient in DNA ligase 4 and XPF-ERCC1 exhibit further impaired class switching, reducing joining to the resected S region DSBs without altering the MH pattern in S-S junctions. In ERCC1-deficient A-EJ cells, 3′ single-stranded DNA (ssDNA) flaps that are generated predominantly in S/G2 phase of the cell cycle are susceptible to nuclease resolution. Moreover, ERCC1 promotes c-myc-IgH translocation in Lig4−/− cells. Our study reveals an important role of the flap endonuclease XPF-ERCC1 in A-EJ and oncogenic translocation in mouse B cells.

Thymol is a phenol monoterpene with potential antifungal, antioxidant and antibacterial activities. Due to the low water solubility and high volatility of thymol, encapsulation serves as an effective tool during application. In the present study, cyclodextrin (CD)-based metal-organic-frameworks (MOFs) were synthesized using α-CD, β-CD, and γ-CD as organic building blocks, and further complexed with thymol to produce three CD-MOF-THY inclusion complexes (ICs). The encapsulation content, release kinetics and fruit preservation effect of ICs were analyzed. Results showed that thymol was well embedded in γ-CD-MOFs, with the highest encapsulation content of 286.7 ± 8.4 mg/g. Release kinetics revealed that CD-MOFs exhibited a controlled release effect toward thymol for 35 days. The release kinetics of three ICs fit the Rigter–Peppas model well, with γ-CD-MOF-THY showing the lowest release rate constant of 2.85 at 50 °C, RH 75%. Moreover, γ-CD-MOF-THY exhibited a remarkable preservation performance on cherry tomatoes with the lowest decay index (18.75%) and weight loss (5.17%) after 15 days of storage, suggesting this material as a potential fresh-keeping material for fruit and vegetable preservation.

As a unique landform in the island and reef area, the newborn sandbank is not only the initial stage of island development, but also has a rapid evolution and a complex dynamic mechanism. However, the dynamic geomorphology mechanism of the newborn sandbank is still lacking extensive study and direct evidence of the interaction process between the marine dynamics and the newborn sandbank geomorphology. Therefore, in order to reveal the interaction mechanisms between marine dynamics and newborn sandbanks, a newborn sandbank in the sea area of the Xisha Islands, in the South China Sea, has been selected as the focus of this research. The method of numerical simulation was used to discuss and analyze the wave field characteristics around the newborn sandbank and their impacts on the sandbank’s migration and development. The results show that: (1) The islands and reefs have significant refraction, diffraction, and energy dissipation effects on waves, and the newborn sandbank has the same effect, but with a weaker function. The wave height around the reef islands reduced by approximately 60–67% in dominated and strong wave directions. At the same time, the wave height attenuation in the wave shadow zone, behind the newborn sandbank, can reach approximately 27–33%. (2) Wind is important for the evolution of wave fields; in particular, when the wind speed exceeds grades four and five, the effect of the wind on the waves is particularly significant, causing the winds to control the wave characteristics around the islands and newborn sandbanks. This results in significant seasonal differences in wave fields within the sea area. (3) The wave direction primarily controls the migration direction of the newborn sandbank, and the wave height primarily controls the migration speed and distance. After one month of wave action in the strong wave direction, the maximum eastward deposition length was approximately 50 m. After one month of wave action in the dominated wave direction, the maximum eastward deposition length was approximately 60 m. Therefore, the topography of the newborn sandbank affects the wave propagation, meanwhile, the wave conversely determines migration and development of the newborn sandbank in a short term. The dynamic geomorphology action between the wave and newborn sandbank is a fast two-way process, and occurs not only during storms or the winter monsoon, but also during other, more common, weather events.

Fatty acid and retinol binding proteins (FAR) are unique proteins found in nematodes and are considered potential targets for controlling these parasites. However, their functions in nematode parasitism and pathogenicity and interaction with hosts are still unclear. In this study, we investigated the specific roles of rice white tip nematodes (RWTNs), Aphelenchoides besseyi, and a protein, Ab-FAR-1, to elucidate the parasitic and pathogenic processes of nematodes. The results showed that the expression level of Ab-far-1 was significantly up-regulated after A. besseyi infection of the plant. The immunofluorescence and subcellular localisation showed that Ab-FAR-1 was secreted into plant tissues mainly through the body wall of nematodes and might act in the nucleus and cytoplasm of plant cells. The pathogenicity of RWTNs was enhanced in Arabidopsis thaliana overexpressing Ab-FAR-1 and inhibited in Ab-far-1 RNAi A. thaliana. Yeast two-hybrid, Co-IP, BiFC, and nematode inoculation experiments showed that Ab-FAR-1 could interact with the A. thaliana actin-depolymerizing factor protein AtADF3, and the A. thaliana adf3 mutant was more susceptible to nematodes. An in vitro actin filament depolymerisation assay demonstrated that Ab-FAR-1 could inhibit AtADF3-mediated depolymerisation of actin filaments, and the turnover process of cellular actin filaments was also affected in A. thaliana overexpressing Ab-FAR-1. In addition, flg22-mediated host defence responses were suppressed in A. thaliana overexpressing Ab-FAR-1 and adf3 mutants. Therefore, this study confirmed that RWTNs can affect the turnover of actin filament remodelling mediated by AtADF3 through Ab-FAR-1 secretion and thus inhibit plant PAMP-triggered immunity (PTI), promoting the parasitism and pathogenicity of nematodes.

Breastfeeding is critically important to maternal and child health in the United States. Examining the relationship between breastfeeding outcomes and state policies requires multidisciplinary efforts to link data from various sources. This article describes an integrated dataset that was used to understand the relationship between participation in a nutrition assistance program and low-income children's breastfeeding outcomes [1]. This dataset merged public health information from the National Immunization Surveys Data from 2006 to 2016 and matching state policy data from the Correlates of State Policy Project (CSPP), the U.S. Department of Agriculture/Economic Research Services (USDA/ERS) Supplemental Nutrition Assistance Program (SNAP) Policy Index, the U.S. Bureau of Labor Statistics (BLS), Centers for Medicare & Medicaid Services (CMS), and the Census Bureau. The integrated dataset compiles variables in breastfeeding outcome, child's and mother's socio-demographic characteristics, and state-level policy measures, including SNAP participation rates, SNAP policy indices, unemployment rates, and Children's Health Insurance Program (CHIP) enrollment rates. This multidisciplinary dataset included information on a total of 219,904 children with 98 variables.

Objectives: Maternal cigarette smoke exposure (SE) causes intrauterine undernutrition, resulting in increased risk for metabolic disorders and type 2 diabetes in the offspring without sex differences. L-leucine supplementation has been shown to reduce body weight and improve glucose metabolism in both obese animals and humans. In this study, we aimed to determine whether postnatal L-leucine supplementation in female offspring can ameliorate the detrimental impact of maternal SE.Methods: Female Balb/c mice (6-week) were exposed to cigarette smoke (SE, 2 cigarettes/day) prior to mating for 5 weeks until the pups weaned. Sham dams were exposed to air during the same period. Half of the female offspring from the SE and SHAM dams were supplied with L-leucine via drinking water (1.5% w/w) after weaning (21-day) for 10 weeks and sacrificed at 13 weeks (adulthood).Results: Maternal SE during pregnancy resulted in smaller body weight and glucose intolerance in the offspring. L-leucine supplement in Sham offspring reduced body weight, fat mass, and fasting blood glucose levels compared with their untreated littermates; however somatic growth was not changed. L-leucine supplement in SE offspring improved glucose tolerance and reduced fat mass compared with untreated littermates.Conclusions: Postnatal L-leucine supplement could reduce fat accumulation and ameliorate glucose metabolic disorder caused by maternal SE. The application of leucine may provide a potential strategy for reducing metabolic disorders in offspring from mothers who continued to smoke during pregnancy.

The rapidly increasing prevalence of Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing bacteria has become a serious challenge to public health. Currently, the blaKPC–2 gene is mainly disseminated through plasmids of different sizes and replicon types. However, the plasmids carrying the blaKPC–2 gene have not been fully characterized. In this study, we report the complete genome sequences of two novel blaKPC–2-harboring incompatibility group U (IncU) plasmids, pEC2341-KPC and pEC2547-KPC, from international high-risk clones of Escherichia coli isolated from Zhejiang, China. Two KPC-2-producing E. coli isolates (EC2341 and EC2547) were collected from clinical samples. Whole-genome sequencing (WGS) analysis indicated that EC2341 and EC2547 belonged to the ST410 and ST131 clones, respectively. S1-nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot and conjugation experiments confirmed the presence of the blaKPC–2 gene on the pEC2341-KPC plasmid and that this was a conjugative plasmid, while the blaKPC–2 gene on the pEC2547-KPC plasmid was a non-conjugative plasmid. In addition, plasmid analysis further revealed that the two blaKPC–2-harboring plasmids have a close evolutionary relationship. To the best of our knowledge, this is the first report of E. coli strains carrying the blaKPC–2 gene on IncU plasmids. The emergence of the IncU-type blaKPC–2-positive plasmid highlights further dissemination of blaKPC–2 in Enterobacteriaceae. Therefore, effective measures should be taken immediately to prevent the spread of these blaKPC–2–positive plasmids.

The solid solution strengthening of Li, Mg, Al, Mn, Cu and Ag in biodegradable Zn-based alloys is quantitatively investigated by first-principles calculations based on density functional theory. The alloying effect on lattice parameters and elastic constants is determined. Mn is found to have the greatest impact on the lattice parameters and shear modulus, while Mg and Al exhibit the least. According to the theories proposed by Fleischer and Labusch, the strengthening capability of selected elements can be ranked as Mn > Li > Cu, Ag > Mg > Al. The different strengthening effect of solutes can be attributed to their valence electron structure. Analysis on experimental results indicates that ternary Zn-based alloys may satisfy the clinical requirements on mechanical properties with less secondary phase and suppressed mechanical instability.

Elderly with comorbidities have shown a higher rate of fatal outcomes when suffering coronavirus disease 2019 (COVID-19). However, a delineation of clinical significances of hematologic indices and underlying comorbidities in the progression and outcome of COVID-19 remains undefined. Six hundred two COVID-19 patients with established clinical outcomes (discharged or deceased) from Hankou Hospital of Wuhan, China between January 14, 2020 and February 29, 2020 were retrospectively analyzed. Of the 602 patients with COVID-19, 539 were discharged and 63 died in the hospital. The deceased group showed higher leukocyte and neutrophil counts but lower lymphocyte and platelet counts. Longer activated partial thromboplastin time (APTT) and prothrombin time (PT), as well as higher D-dimer and C-reactive protein levels, were found in non-survivors. Our observations suggest that these parameters could serve as potential predictors for the fatal outcome and in the discharged group. A higher neutrophil count and D-dimer level but lower lymphocyte were associated with a longer duration of hospitalization. A multivariable Cox regression analysis showed that higher neutrophil count, prolonged PT, and low lymphocyte count were risk factors for patients with COVID-19. Also, we found an association of lower lymphocyte count and higher C-reactive protein levels with the elderly group and those with cardiovascular-related comorbidities. The significantly different hematologic profiles between survivors and non-survivors support that distinct hematologic signatures in COVID-19 patients will dictate different outcomes as a prognostic marker for recovery or fatality. Lymphopenia and aggressive inflammatory response might be major causes for fatal outcomes in the elderly male and especially those with cardiovascular-related comorbidities.

Self-regulatory learning skills are recognized as an essential factor motivating students to learn. The lack of self-regulatory learning skills could reduce students' learning performance. Therefore, engaging students in making learning plans, executing the plans, and reflecting on their learning remains a challenge for teachers. To address this problem, this study proposes a gamified mobile self-regulated learning approach which provides multiple gamified rewards to motivate students' self-regulatory learning skills. Gamified elements were integrated into students' self-regulated learning stages to guide them in efficiently exploring how to achieve their goals and making deep learning reflections. To investigate the effect of this proposed approach on students' learning outcomes, two classes of students were recruited to conduct the experiment. The learning approach was used by the experimental group (N = 22) while the conventional mobile self-regulated learning approach was used by the control group (N = 22). Both groups of students' performance on the mathematics learning achievement test, SRL learning sheets, and goal-achieving intentions were collected and analyzed. The results showed that the gamification mechanism improved the students' learning achievement as well as their goal-setting and reflection performance. However, the students who used the proposed approach reached similar monitoring performance as those students who learned without gamification. This study confirmed the feasibility of introducing a gamification mechanism into self-regulated learning, and revealed how to apply multiple game elements in instructional activities to enhance students' learning intentions.

An organic chemistry experiment designed for senior undergraduates focuses on bifunctional catalysis, a critical yet often omitted topic at the undergraduate level, but essential for advanced studies in chemistry. By utilization of a tertiary amine-thiourea catalyst in the asymmetric Michael addition reaction, the experiment showcases the superiority of bifunctional catalysis over traditional monofunctional approaches. Comprehensive training in designing control experiments, performing flash chromatography, and analyzing results with NMR and HPLC techniques equip students with modern synthetic skill sets. This experiment features easy operation and a relatively short time (4.5h, including 2-2.5 h reaction time). More importantly, it bridges the educational gap in understanding advanced catalytic mechanisms and techniques in organic chemistry.

Abstract Background The increasing trend of Caesarean section (CS) in childbirth has become a global public health challenge. Previous studies have proposed financial intervention strategies for reducing CS rates by limiting caesarean delivery on maternal request (CDMR). This study synthesizes such strategies while evaluating their effectiveness. Methods The sources of data for this study are Cochrane Library, PubMed, EMBASE, and CINAHL. The publication period included in this study is from January 1991 to November 2018. The financial intervention strategies are divide into two categories: healthcare provider interventions and patient interventions. Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) was employed to assess the risk of bias of included studies. The outcome of each study was evaluated with Grades of Recommendation, Assessment, Development and Evaluation (GRADE) through the GRADEpro Guideline Development Tool software. Results Nine studies were included in this systematic review: five with high certainty evidence (HCE), three with moderate certainty evidence (MCE), and one with low certainty evidence (LCE). Of the nine studies, seven are centered on the effect of provider-side interventions. Three of the HCE studies found that the diagnosis-related group payment system, risk-adjusted capitation, and equalizing fee for both facilities and physicians were effective intervention strategies. One HCE and one MCE study showed that only equalizing facility fees between vaginal and CS deliveries in healthcare service settings had no significant effect on reducing the CS rate. The MCE study showed that case payment had a negative effect on reducing the CS rates. One LCE study revealed that the effect of a global budget system was uncertain, and one HCE and one MCE study focused on combining both provider and patient-side interventions. However, equalizing fees for vaginal and CS deliveries and a co-payment policy for CDMRs failed to reduce the CS rate. Conclusions The effectiveness of risk-adjusted payment methods appears promising and should be the subject of further research. Financial interventions should consider stakeholders’ characteristics, especially the personal interests of doctors. Finally, high-quality randomized control trials and comparative studies on different financial intervention methods are needed to confirm or refute previous studies’ outcomes.

A novel polysaccharide (MFP4P) was isolated from mulberry fruits (Morus alba L.) pulp using a combination of DEAE-Sepharose fast-flow and Sephadex G-100 chromatographic columns. Structural characterization revealed that MFP4P was composed of arabinose, rhamnose, galactose, glucose and galacturonic acid with a molecular weight of 198.2 kDa. The linkage types of MFP4P were proved to be (1 → 6)-linked α-D-Glc, (1 → 2)-linked α-L-Rha, (1 → 3)-linked α-D-Gal, (1 → 3)-linked β-L-Rha and (1 → )-linked α-L-Ara. The MFP4P showed good antioxidant activity with an oxygen radical absorbance capacity value of 121.8 ± 16.5 μM trolox equivalent/g. In addition, the MFP4P promoted pancreatic cell proliferation, increased insulin secretion, and enhanced glucose consumption. In the non-toxic range, the polysaccharide and zinc complexes (MFP4P-Zn) exhibited higher antioxidant and hypoglycemic activities than MFP4P at the same concentration. In vivo hypoglycemic study, MFP4P and MFP4P-Zn both showed decreased blood glucose level and glucose tolerance compared with the model control group.