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AimsTo investigate the epidemiological and clinical characteristics of children with Mycoplasma pneumoniae pneumonia (MPP) in Hubei, China.MethodsWe retrospectively analyzed inpatients with MPP from 20 hospitals in Hubei, China from January 2021 to December 2022. The co-detected pathogens of Mycoplasma pneumoniae (M. pneumoniae) were investigated using targeted next-generation sequencing (tNGS), and 23S rRNA gene mutations were analyzed to assess the macrolide resistance.ResultsM. pneumoniae infected 20.7% of patients with CAP, with cough (96.59%) and fever (80.28%) being the most prevalent symptoms. The infection rates in children younger than 1, 1–2, 3–6, 7–12, and older than 12 years were 6.17%, 19.98%, 26.97%, 43.93%, and 2.95%, respectively. Among 1,349 patients undergoing tNGS, the overall co-detection rate was 59.45%, with Streptococcus pneumoniae (29.30%), Haemophilus influenzae (23.57%), and Human rhinovirus (17.21%) being the most commonly co-detected pathogens. In 635 patients undergoing the 23S rRNA gene mutation test, 86.30% exhibited positive mutations (A2063G, 98.00%; A2064G, 1.50%; A2067G, 0.50%). Despite a significant age difference (P = 0.037) between macrolide-resistant M. pneumoniae and macrolide-sensitive M. pneumoniae groups, there were no significant differences in symptoms, lab data, or disease severity.ConclusionsIn Hubei Province, the prevalence of exhibited consistent changes during the COVID-19 pandemic. MPP was prevalent year-round, particularly in summer and autumn, with school-age children being more susceptible. Co-detections of viruses and bacteria were frequent in MPP cases, and macrolide resistance exceeded 85%. Ongoing surveillance of M. pneumoniae in children is crucial for understanding the healthcare impact of MPP.

A rapid and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous determination of doxorubicin (DOX) in mouse plasma and tissues, including the heart, liver, spleen, lung, kidney and tumor, and to investigate the pharmacokinetics and distribution in mice. In this study, daunorubicin (DNR) was used as an internal standard, and the mobile phase consisted of ammonium formate 2 mM containing 0.1 % formic acid (A) and acetonitrile (B), the chromatographic column was ACQUITY UPLC BEHTM C18 with a gradient elution at a flow rate of 0.2 mL/min. Electrospray ionization (ESI) in positive ion pattern was utilized for the ion separation of DOX, with the ions used for quantitative analysis being DOX m/z 544.28 → 397.10 and DNR m/z 528.35 → 321.08, respectively. The results showed that a good linear relationship in the calibration curve range of 1–800 ng/mL in mouse plasma and 1–2500 ng/g in tissues (R2 > 0.99) with the limits of quantification of 1 ng/mL in plasma and tissues. The method exhibited good matrix effect and extraction recovery, with the intra-day and inter-day precision of plasma and tissue were less than 10.3 % and 15.4 %, and the relative error (RE) were both less than ±14.8 % and ±18.9 %, respectively. The stability results under different conditions were found to be accurate. It also revealed the distribution of DOX in various tissues of mice, with the concentration ranking as liver > heart > kidney > spleen > lung > tumor. This method was successfully used to the study for the pharmacokinetics in plasma and drug distribution in tissues of BALB/c mice.

Extreme heat events caused by climate change have seriously threatened the sustainable human-environment system development. It has become the frontier of integrated geography to scientifically assess the comprehensive impact of heat waves on the urban system and to provide stakeholders with decision support services to cope with extreme heat. This study constructed an "exposure-susceptibility-adaptive capacity" framework for urban heat vulnerability and an early warning index system based on the perspective of the human-environment system. We then proposed key early warning technologies, including an urban heat index model, multi-subject adaptive capacity coupling technology, and a multi-group vulnerability assessment criteria library. Taking urban diversified groups and urban administrators as the service target, we designed the urban heat vulnerability early warning system. The system mainly comprises a mobile application that provides users with an interactive interface, and a dedicated management backend. The mobile application has four main functions: Urban heat index forecast, Crowd heat vulnerability risk warning service, Outdoor work guidance service, and Public facility-assisted adaptation and decision support menu. The layer data and the warning message are mainly handled by the dedicated management backend. The system provides hourly location-based heat vulnerability warnings and targeted healthy living tips for tourists, the elderly, children, and people with heat-sensitive conditions. Additionally, the system can provide a scientific basis for communities to improve their adaptive capacity to heat waves. As a pilot, the system was deployed in Xiamen City to provide personalized support services for healthy living in hot weather to residents and communities. In September 2021, the "Urban Heat Index" module was officially launched on the "Zhi Tian Qi" public meteorological service platform of the Fujian Province. The research perspective and methodology, based on a multiscale vulnerability framework, provide an effective method to dynamically and finely characterize the impacts of extreme natural hazards. The research results support urban multi-stakeholders in managing production and life during hot weather and help authorities develop targeted disaster prevention and mitigation plans for specific areas. Moreover, the findings provide a scientific reference for planning departments to improve and optimize the spatial allocation of emergency resources.

Abstract Hydraulic fracturing and waterflooding are both widely applied methods for improving the recovery of oil and gas resources. These methods have increasing commonality because many waterfloods are being carried out at high enough pressure to generate hydraulic fractures. Even so, it is challenging for engineers to make an optimal wellbore pressure design for layered and otherwise complex underground formations. An overly aggressive injection pressure may lead to uncontrollable fracture height growth into non-producing layers adjacent to the reservoir. In contrast, when using classical but highly simplified height growth models, the pressure limits can be far too conservative which may lead to lower recovery rates and inefficient use of resources invested in developing producing reservoirs. Therefore, it is necessary to investigate the mechanism of fracture height growth while considering the coupling effect from multiple dominated factors. This research contributes an experimental approach to evaluating the role of stresses, weak interfaces, and mechanical properties of a three-layer system in promoting or containing hydraulic fracture height growth from a central reservoir into neighboring barrier layers. In all cases, the experiments agree that the pressure required to induce substantial height growth exceeds the stress applied to the barrier layers and is far above classical predictions. Additionally, when the reservoir layer is softer than the barriers, the containment is sustained to even higher pressures than for layers with similar material properties. Finally, the experiments show that permeability of the barrier layer can induce a more sudden transition to uncontrolled height growth when fracture reaches the bedding interfaces. Hydraulic fracture height growth is mitigated by weak interfaces between layers. Unstable height growth typically requires fluid pressure to exceed the in-situ stress in the bounding layer(s). Contrasting layer stiffness and permeability often leads to further mitigation of height growth.

Objective To investigate the effect of thrombospondin-1(TSP-1) knockout on radiation-induced pulmonary fibrosis and explore its underlying mechanism. Methods Male wild type C57BL/6 mice (6~8 weeks old, WT mice) and TSP-1 knockout mice (TSP-1-/- mice) were subjected and received 16 Gy 60Co γ-ray whole lung irradiation (IR) to induce radiation pulmonary fibrosis, and then, the mice were assigned into WT+IR group and TSP-1-/-+IR group, respectively, with 6 mice in each group.In 16 weeks after irradiation, HE staining was performed to observe the morphological changes in lung tissues, and Sirius red staining was used to observe the collagen expression in lung tissues.qRT-PCR was employed to detect the mRNA expression of TGF-β1 and Collagen Ⅰ in lung tissues.Micro-CT scanning was adopted to evaluate lung injury and substantial lung changes.FlexiVent system was employed to assess pulmonary function.Immunofluorescence staining was conducted to measure the protein levels of LC-3 and p62 in lung tissues.Transmission electron microscopy (TEM) was used to observe the cellular autophagic vesicles in lung tissues. Results Compared with the WT+IR group, the TSP-1-/-+IR group had reduced lung injury and collagen deposition in lung tissue, significantly lower mRNA levels of TGF-β1 and Collagen Ⅰ in lung tissue (P < 0.01), and improved pulmonary function.Immunofluorescence assay and TEM showed that autophagy was observed in the mice of TSP-1-/-+IR group. Conclusion TSP-1 knockout can alleviate radiation-induced pulmonary fibrosis, which may be related to activation of autophagy.

In order to understand the electrochemical oxidation mechanism of oxalic acid on platinum, glassy carbon and boron doped diamond(BDD) electrodes in nitric acid medium, cyclic voltammetry and linear sweep voltammetry were used to carry out electrochemical tests. The effects of electrode potential, current density and nitric acid concentration on oxalic acid oxidation were studied, and the influence of nitric acid mainly comes from H+. On the Pt electrode, it is speculated that oxalic acid is not only electrooxidized, but also adsorbed ·OH reacts with adsorbed oxalic acid to produce CO2 and H2O. On the boron doped diamond electrode, indirect oxidation of ·OH is the main role of oxalic acid oxidation. The increase of nitric acid concentration reduces the amount of ·OH production, which leads to the decrease of oxalic acid oxidation rate. On the glassy carbon electrode, the diffusion coefficient of oxalic acid is 1.4×10-5 cm2/s measured by rotating disc electrode, the exchange current density of oxalic acid electrochemical oxidation obtained by Tafel extrapolation at 1.34-1.42 V is 5.8×10-6 A/cm2.

Percolation, describing critical behaviors of phase transition in a geometrical context, prompts wide investigations in natural and social networks as a fundamental model. The introduction of quantum coherence and superposition brings percolation into quantum regime with more fascinating phenomena and unique features, which, however, has not been experimentally explored yet. Here we successfully map these large-scale porous structures into a photonic chip using femtosecond laser direct writing techniques and present an experimental demonstration of quantum transport in hexagonal percolation lattices, probed by coherent light. A quantum percolation threshold of 80% is observed in the prototyped laser-written lattices with up to 1,600 waveguides, which is significantly larger than the classical counterpart of 63%. We also investigate the spatial confinement by localization parameters and exhibit the transition from ballistic to diffusive propagation with the decrease of the occupation probability. Direct observation of quantum percolation may deepen the understanding of the relation among materials, quantum transport, geometric quenching, disorder and localization, and inspire applications for quantum technologies.

With its high resolving power and sensitivity, mass spectrometry is considered the most informative technique for metabolite qualitation and quantification in the plant sciences. However, the spatial location information, which is crucial for the exploration of plant physiological mechanisms, is lost. Mass spectrometry imaging (MSI) is able to visualize the spatial distribution of a large number of metabolites from the complex sample surface in a single experiment. In this paper, a flexible and low-cost laser desorption–dielectric barrier discharge ionization-MSI (LD-DBDI-MSI) platform was constructed by combining an LD system with an in-line DBDI source, a high-precision sample translation stage, and an ambient mass spectrometer. It can be operated at a spatial resolution of 20 μm in an atmospheric environment and requires minimal sample preparation. This study presents images of in-situ metabolic profiling of two kinds of plants from different origins, a wild and a farmed Rheum palmatum L. From the screen of these two root sections, the wild one presented five more endogenous molecules than the farmed one, which provides information about the differences in metabolomics.

We study how Cas9, a central component of the CRISPR/Cas9 system, searches for a target sequence on the DNA. We propose a model that includes as key ingredients 3D diffusion, 1D sliding along the DNA, and the effect of short binding sequences preceding the target (protospacer adjacent motifs—PAMs). This last aspect constitutes the main difference with traditional facilitated diffusion of transcription factors. We solve our model, obtaining an expression for the average search time of Cas9 for its target. We find that experimentally measured kinetic parameters are close to the values yielding an optimal search time. Our results rationalize the role of PAMs in guiding the search process, and show that Cas9 searches for its targets in a nearly optimal way.

Abstract The aim of the study was to assess the factors associated with periodic limb movements during sleep (PLMS) among obstructive sleep apnea syndrome (OSAS) patients and identify the role of PLMS in patients with OSAS. 303 adult patients with OSAS were included in the study. All patients completed physical examination, Epworth sleepiness scale (ESS), and polysomnography. Diagnosis of PLMS was made if the periodic leg movements index (PLMI) was ≥ 15. Chi-square test, ANOVA, univariate and multivariate logistic regression analyses were conducted to identify factors associated with PLMS among OSAS patients. Statistical analyses were performed with SPSS 26.0 for mac. Statistically significant difference was considered if P value

The widespread deficiency of iron (Fe) and sulfur (S) is becoming a global concern. The underlying mechanisms regulating Fe and S sensing and signaling have not been well understood. We investigated the crosstalk between Fe and S using mutants impaired in Fe homeostasis, sulfate assimilation, and glutathione (GSH) biosynthesis. We showed that chlorosis symptoms induced by Fe deficiency were not directly related to the endogenous GSH levels. We found dynamic crosstalk between Fe and S networks and more interestingly observed that the upregulated expression of IRT1 and FRO2 under S deficiency in Col-0 was missing in the cad2-1 mutant background, which suggests that under S deficiency, the expression of IRT1 and FRO2 was directly or indirectly dependent on GSH. Interestingly, the bottleneck in sulfite reduction led to a constitutively higher IRT1 expression in the sir1-1 mutant. While the high-affinity sulfate transporter (Sultr1;2) was upregulated under Fe deficiency in the roots, the low-affinity sulfate transporters (Sultr2;1, and Sultr2;2) were down-regulated in the shoots of Col-0 seedlings. Moreover, the expression analysis of some of the key players in the Fe–S cluster assembly revealed that the expression of the so-called Fe donor in mitochondria (AtFH) and S mobilizer of group II cysteine desulfurase in plastids (AtNFS2) were upregulated under Fe deficiency in Col-0. Our qPCR data and ChIP-qPCR experiments suggested that the expression of AtFH is likely under the transcriptional regulation of the central transcription factor FIT.

Abstract Obstructive sleep apnea syndrome (OSAS) is underdiagnosed in females and gender differences in clinical and polysomnographic findings have not been widely investigated in China. We examined clinical and polysomnographic differences between males and females with OSAS in order to determine the influence of gender on clinical presentation and polysomnographic features. Data were collected from 303 adult patients diagnosed with OSAS (237 males and 66 females) from 2017 to 2019. All the patients completed physical examination, Epworth sleepiness scale, and whole night polysomnography. AVONA, univariate and multivariate logistic regression analyses were conducted to assess gender differences of clinical and polysomnographic findings with OSAS. P

Background and Objective: Since the classification of gaming disorder (GD) by the World Health Organization (WHO) as “mental disorder caused by addictive behaviors,” there has been controversy regarding whether online game behaviors can lead to mental disorder. This study aims to clarify the correlation between the online game behaviors of college students and anxiety, depression, and executive function of college students in China, from a questionnaire-based investigation.Methods: Based on the whole class random sampling method, a questionnaire survey was conducted among college students in Northern Anhui, China from March 7 to March 27, 2020. The questionnaires included the Internet Game Addiction (IGA) Scale, Behavior Rating Inventory of Executive Function (Adult Version, BRIEF-A), Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire Scale (PHQ-9).Results: A total of 850 participants completed the survey, including 353 males (41.53%) and 497 females (58.47%). The primary age group was 18–27 years (91.53%), and the educational background was a bachelor's degree (94.7%). The study found that the online behavior of 17.76% of college students was online game behavior. This study did not identify any students who met the criteria for IGA, and 3% met the criteria for indulgent behavior. A dual role of online games was identified; moderate online game activities can improve the emotional state and executive function of college students, while excessive online game behaviors that may not reach the degree of addiction can also harm emotional state and executive function.Conclusions: This study suggests that although IGA has been regarded as a mental disease, online game behavior should be treated differently. Online game activities should not be entirely denied, but mental disorders caused by excessive gaming activities deserve attention. In particular, the emotional state and executive function of students with excessive online game behaviors should be monitored and intervened in advance to avoid game behaviors turning into indulgent behaviors or addiction. As a cognitive control process, executive function may play a key role in regulating IGA and emotional state.

Recent advances in communication enable individuals to use phones and computers to access information on the web. E-commerce has seen rapid development, e.g., Alibaba has nearly 12 hundred million customers in China. Click-Through Rate (CTR) forecasting is a primary task in the e-commerce advertisement system. From the traditional Logistic Regression algorithm to the latest popular deep neural network methods that follow a similar embedding and MLP, several algorithms are used to predict CTR. This research proposes a hybrid model combining the Deep Interest Network (DIN) and eXtreme Deep Factorization Machine (xDeepFM) to perform CTR prediction robustly. The cores of DIN and xDeepFM are attention and feature cross, respectively. DIN follows an adaptive local activation unit that incorporates the attention mechanism to adaptively learn user interest from historical behaviors related to specific advertisements. xDeepFM further includes a critical part, a Compressed Interactions Network (CIN), aiming to generate feature interactions at a vectorwise level implicitly. Furthermore, a CIN, plain DNN, and a linear part are combined into one unified model to form xDeepFM. The proposed end-to-end hybrid model is a parallel ensemble of models via multilayer perceptron. CIN and xDeepFM are trained in parallel, and their output is fed into a multilayer perceptron. We used the e-commerce Alibaba dataset with the focal loss as the loss function for experimental evaluation through online complex example mining (OHEM) in the training process. The experimental result indicates that the proposed hybrid model has better performance than other models.

This study aimed at determining the beneficial effect of Clostridium butyricum (CB) RH2 on ceftriaxone-induced dysbacteriosis. To this purpose, BALB/c mice were exposed to ceftriaxone (400 mg/ml) or not (control) for 7 days, and administered a daily oral gavage of low-, and high-dose CB RH2 (108 and 1010 CFU/ml, respectively) for 2 weeks. CB RH2 altered the diversity of gut microbiota, changed the composition of gut microbiota in phylum and genus level, decreased the F/B ratio, and decreased the pro-inflammatory bacteria (Deferribacteres, Oscillibacter, Desulfovibrio, Mucispirillum and Parabacteroides) in ceftriaxone-treated mice. Additionally, CB RH2 improved colonic architecture and intestinal integrity by improving the mucous layer and the tight junction barrier. Furthermore, CB RH2 also mitigated intestinal inflammation through decreasing proinflammatory factors (TNF-α and COX-2) and increasing anti-inflammatory factors (IL-10). CB RH2 had direct effects on the expansion of CD4+ T cells in Peyer’s patches (PPs) in vitro, which in turn affected their immune response upon challenge with ceftriaxone. All these data suggested that CB RH2 possessed the ability to modulate the intestinal mucosal and systemic immune system in limiting intestinal alterations to relieve ceftriaxone-induced dysbacteriosis.

The mechanism of protein dislocation into the cytosol during antigen cross-presentation is poorly understood. Here the authors engineer a dislocation reporter fusing a glycosylated luciferase variant to the Fc region of IgG1, and find that dislocation is the rate limiting step in cross-presentation.

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical phenotypes. The missense variants in individuals with CDH are located within the actin-binding domains of the protein but are not predicted to affect protein structure, whereas the variants in individuals with osteoporosis are predicted to result in loss of function. A mouse knockin model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Both the mouse model and one adult human male with a CDH-associated PLS3 variant were observed to have increased rather than decreased bone mineral density. Together, these clinical and functional data in humans and mice reveal that specific missense variants affecting the actin-binding domains of PLS3 might have a gain-of-function effect and cause a Mendelian congenital disorder.

Human induced pluripotent stem cells (hiPSCs) have potential applications in cell replacement therapy and regenerative medicine. However, limited information is available regarding the immunologic features of iPSCs. In this study, expression of MHC and T cell co-stimulatory molecules in hiPSCs, and the effects on activation, proliferation and cytokine production in allogeneic human peripheral blood mononuclear cells were examined. We found that no-integrate hiPSCs had no MHC-II and T cell co-stimulatory molecules expressions but had moderate level of MHC-I and HLA-G expressions. In contrast to human skin fibroblasts (HSFs) which significantly induced allogeneic T cell activation and proliferation, hiPSCs failed to induce allogeneic CD45+ lymphocyte and CD8+ T cell activation and proliferation but could induce a low level of allogeneic CD4+ T cell proliferation. Unlike HSFs which induced allogeneic lymphocytes to produce high levels of IFN-γ, TNF-α and IL-17, hiPSCs only induced allogeneic lymphocytes to produce IL-2 and IL-10, and promote IL-10-secreting regulatory T cell (Treg) generation. Our study suggests that the integration-free hiPSCs had low or negligible immunogenicity, which may result from their induction of IL-10-secreting Treg.

Hepatic stellate cells (HSCs) play a key role in the development of liver fibrosis caused by schistosomiasis. Chemokines were widely expressed and involved in cellular activation, proliferation and migration in inflammatory and infectious diseases. However, little is known about the expressions of chemokines on HSCs in the schistosoma infection. In addition, the roles of chemokines in pathogenesis of liver fibrosis are not totally clear. In our study, we used microarray to analyze the temporal gene expressions of primary HSCs isolated from mice with both acute and chronic schistosomiasis. Our microarray data showed that most of the chemokines expressed on HSCs were upregulated at 3 weeks post-infection (p.i) when the egg granulomatous response was not obviously evoked in the liver. However, some of them like CXCL9, CXCL10 and CXCL11 were subsequently decreased at 6 weeks p.i when the granulomatous response reached the peak. In the chronic stage, most of the differentially expressed chemokines maintained persistent high-abundances. Furthermore, several chemokines including CCR2, CCR5, CCR7, CXCR3, CXCR4, CCL2, CCL5, CCL21, CXCL9 and CXCL10 were expressed by HCSs and the abundances of them were changed following the praziquantel treatment in the chronic stage, indicating that chemokines were possibly necessary for the persistence of the chronic stage. In vitro experiments, hepatic non-parenchymal cells, primary HSCs and human HSCs line LX-2 were stimulated by chemokines. The results showed that CXCL9 and CXCL10, but not CXCL11 or CXCL4, significantly inhibited the gene expressions of Col1α1, Col3α1 and α-SMA, indicating the potential anti-fibrosis effect of CXCL9 and CXCL10 in schistosomiasis. More interestingly, soluble egg antigen (SEA) of Schistosoma japonicum was able to inhibit transcriptional expressions of some chemokines by LX-2 cells, suggesting that SEA was capable of regulating the expression pattern of chemokine family and modulating the hepatic immune microenvironment in schistosomiasis.