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Background Although headache disorders are common, the current diagnostic approach is unsatisfactory. Previously, we designed a guideline-based clinical decision support system (CDSS 1.0) for diagnosing headache disorders. However, the system requires doctors to enter electronic information, which may limit widespread use. Methods In this study, we developed the updated CDSS 2.0, which handles clinical information acquisition via human–computer conversations conducted on personal mobile devices in an outpatient setting. We tested CDSS 2.0 at headache clinics in 16 hospitals in 14 provinces of China. Results Of the 653 patients recruited, 18.68% (122/652) were suspected by specialists to have secondary headaches. According to “red-flag” responses, all these participants were warned of potential secondary risks by CDSS 2.0. For the remaining 531 patients, we compared the diagnostic accuracy of assessments made using only electronic data firstly. In Comparison A, the system correctly recognized 115/129 (89.15%) cases of migraine without aura (MO), 32/32 (100%) cases of migraine with aura (MA), 10/10 (100%) cases of chronic migraine (CM), 77/95 (81.05%) cases of probable migraine (PM), 11/11 (100%) cases of infrequent episodic tension-type headache (iETTH), 36/45 (80.00%) cases of frequent episodic tension-type headache (fETTH), 23/25 (92.00%) cases of chronic tension-type headache (CTTH), 53/60 (88.33%) cases of probable tension-type headache (PTTH), 8/9 (88.89%) cases of cluster headache (CH), 5/5 (100%) cases of new daily persistent headache (NDPH), and 28/29 (96.55%) cases of medication overuse headache (MOH). In Comparison B, after combining outpatient medical records, the correct recognition rates of MO (76.03%), MA (96.15%), CM (90%), PM (75.29%), iETTH (88.89%), fETTH (72.73%), CTTH (95.65%), PTTH (79.66%), CH (77.78%), NDPH (80%), and MOH (84.85%) were still satisfactory. A patient satisfaction survey indicated that the conversational questionnaire was very well accepted, with high levels of satisfaction reported by 852 patients. Conclusions The CDSS 2.0 achieved high diagnostic accuracy for most primary and some secondary headaches. Human–computer conversation data were well integrated into the diagnostic process, and the system was well accepted by patients. The follow-up process and doctor–client interactions will be future areas of research for the development of CDSS for headaches.

The relationship between serum uric acid (SUA) and poor cognitive performance in patients with ischemic stroke is unclear. We hypothesized that the severity of renal function mediates the association between SUA and cognitive dysfunction.A retrospective analysis of 608 patients with ischemic stroke was conducted between 2016 and 2020. SUA was obtained from inpatient medical records. Global cognitive function via mini-mental state exam (MMSE) and Montreal Cognitive Assessment (MoCA) was determined one month after hospital discharge. The relationship between SUA and cognitive function was assessed by multiple linear and logistic regression analyses. Patients had a mean age of 66.6 years (SD: 4.1 years), and 52% were male. The mean SUA level was 298.6 ± 75.4 μmol/L. SUA increases were significantly positively associated with lower MMSE and MoCA scores and increased risk of moderate-severe cognitive impairment one month after stroke (p p-interaction = 0.016) and MoCA (p-interaction = 0.005). In patients with ischemic stroke, SUA showed an inverse association with cognitive function among those who have lower eGFR. The renal function might mediate the association between SUA and cognitive dysfunction.

Background Periodontal ligament stem cells (PDLSCs) are important seed cells for tissue engineering to realize the regeneration of alveolar bone. Understanding the gene regulatory mechanisms of osteogenic lineage differentiation in PDLSCs will facilitate PDLSC-based bone regeneration. However, these regulatory molecular signals have not been clarified. Methods To screen potential regulators of osteogenic differentiation, the gene expression profiles of undifferentiated and osteodifferentiated PDLSCs were compared by microarray and bioinformatics methods, and PSAT1 was speculated to be involved in the gene regulation network of osteogenesis in PDLSCs. Lentiviral vectors were used to overexpress or knock down PSAT1 in PDLSCs, and then the proliferation activity, migration ability, and osteogenic differentiation ability of PDLSCs in vitro were analysed. A rat mandibular defect model was built to analyse the regulatory effects of PSAT1 on PDLSC-mediated bone regeneration in vivo. The regulation of PSAT1 on the Akt/GSK3β/β-catenin signalling axis was analysed using the Akt phosphorylation inhibitor Ly294002 or agonist SC79. The potential sites on the promoter of PSAT1 that could bind to the transcription factor ATF4 were predicted and verified. Results The microarray assay showed that the expression levels of 499 genes in PDLSCs were altered significantly after osteogenic induction. Among these genes, the transcription level of PSAT1 in osteodifferentiated PDLSCs was much lower than that in undifferentiated PDLSCs. Overexpressing PSAT1 not only enhanced the proliferation and osteogenic differentiation abilities of PDLSCs in vitro, but also promoted PDLSC-based alveolar bone regeneration in vivo, while knocking down PSAT1 had the opposite effects in PDLSCs. Mechanistic experiments suggested that PSAT1 regulated the osteogenic lineage fate of PDLSCs through the Akt/GSK3β/β-catenin signalling axis. PSAT1 expression in PDLSCs during osteogenic differentiation was controlled by transcription factor ATF4, which is realized by the combination of ATF4 and the PSAT1 promoter. Conclusion PSAT1 is a potential important regulator of the osteogenic lineage differentiation of PDLSCs through the ATF4/PSAT1/Akt/GSK3β/β-catenin signalling pathway. PSAT1 could be a candidate gene modification target for enhancing PDLSCs-based bone regeneration.

Purpose This study evaluated the clinical safety and efficacy of tanfanercept (HBM9036) ophthalmic solution as a novel treatment for dry eye disease (DED) in a controlled adverse environment (CAE) study conducted in China. Methods In a single-center, double-masked, randomized, placebo-controlled study, 100 patients received 0.25% tanfanercept, or placebo, twice daily for eight weeks. A mobile international CAE® DE Model was used for patient selection with a standardized challenge endpoint. Primary efficacy endpoint was fluorescein inferior corneal staining score (ICSS) pre- to post-CAE challenge from baseline. Secondary endpoints included Schirmer’s Tear Test, Tear-Film Break-Up Time, Ocular Discomfort Score, Ora Calibra® Ocular Discomfort and 4-Symptom Questionnaire, total corneal staining score (TCSS), and drop comfort. Signs and symptoms were assessed both pre- and post-CAE to evaluate the efficacy of tanfanercept on both environmental and CAE endpoints. Results The tanfanercept treatment group showed improvement in ICSS pre- to post-CAE change from baseline scores when compared to placebo (− 0.61 ± 0.11 and − 0.54 ± 0.11, respectively; mean difference = 0.07, p = 0.65). TCSS pre–post-CAE change from baseline scores was also in favor of active when compared to placebo (− 1.03 ± 0.21 and − 0.67 ± 0.21, respectively; mean difference = 0.37, p = 0.23). Schirmer’s score improvement was demonstrated in favor of active (1.87 ± 0.62 mm) as compared to placebo (1.28 ± 0.62 mm; mean difference = 0.59 mm, p = 0.50). Change from baseline in mean Tear-Film Break-up Time favored active treatment over placebo (mean difference = 1.21 s, p = 0.45). Notably, the tanfanercept showed more obvious benefits for each DED sign in a subgroup of subjects ≥ 35 years of age. Tanfanercept was well tolerated with no serious adverse events occurring during the study. Conclusion Tanfanercept demonstrated improvements in favor of active as compared to placebo in the signs of DED, being safe and well tolerated. These data support further evaluation of tanfanercept for the treatment of DED in China. Trial registration This study was retrospectively registered at ClinicalTrials.gov (NCT04092907) on September 17, 2019.

Person re-identification(Re-ID) has been a hot topic in the field of computer vision for the past few years. In order to solve the problem of misalignment between different images, most of the existing algorithms use a certain method to manually divide the image into several parts(such as uniform block, segmentation, and pose estimation model), and then extract local features through a multi-branch network structure. However, the compulsory region division does not give full play to the advantages of the deep learning network’s automatic feature extraction, and will bring additional calculations. This paper designs the architecture of Multi-stage Attention which achieves the goal of automatically extracting the discriminative features with a single branch structure. Meanwhile, there are few such studies that enhance the power of discriminating features by designing loss functions. Triplet loss, one of the most commonly used loss functions, suffers from difficulty of mining hard triplets and time consuming. To address this issue, we propose an innovative loss function, namely Center Triplet Loss(CTL), to learn a center of each class and to find the closest negative sample to the center. The triplet of CTL consists of an anchor and the corresponding center, and the closest negative sample. As a result, the model is easy to train and stable because the sample pairs are no longer randomly selected. Our algorithm(MACTL: Multi-stage Attention and Center Triplet Loss for Person Re-Identication) outperforms state-of-the-art(sota) on the datasets of Market-1501 and DukeMTMC-reID, with less branches and more stable.

β-Glucan from Saccharomyces cerevisiae has been described to be effective antioxidants, but the specific antioxidation mechanism of β-glucan is unclear. The objectives of this research were to determine whether the β-glucan from Saccharomyces cerevisiae could regulate oxidative stress through the Dectin-1/Nrf2/HO-1 signaling pathway in lipopolysaccharides (LPS)-stimulated RAW264.7 cells. In this study, we examined the effects of β-glucan on the enzyme activity or production of oxidative stress indicators in LPS-stimulated RAW264.7 cells by biochemical analysis and the protein expression of key factors of Dectin-1/Nrf2/HO-1 signaling pathway by immunofluorescence and western blot. The biochemical analysis results showed that β-glucan increased the LPS-induced downregulation of enzyme activity of intracellular heme oxygenase (HO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) while decreasing the production of reactive oxygen species (ROS) and malondialdehyde (MDA). Furthermore, immunofluorescence results showed that β-glucan can activate the nuclear factor erythroid 2-related factor 2 (Nrf2). The antioxidant mechanism study indicated that β-glucan activated dendritic-cell-associated C-type lectin 1 (Dectin-1) receptors mediated Nrf2/HO-1 signaling pathway, thereby downregulating the production of ROS and thus produced the antioxidant effects in LPS-stimulated RAW 264.7 cells. In conclusion, these results indicate that β-glucan potently alleviated oxidative stress via Dectin-1/Nrf2/HO-1 in LPS-stimulated RAW 264.7 cells.

This paper consists of two parts. On one hand, the regularity of the solution of the time-fractional Black–Scholes equation is investigated. On the other hand, to overcome the difficulty of initial layer, a modified L1 time discretization is presented based on a change of variable. And the spatial discretization is done by using the Chebyshev Galerkin method. Optimal error estimates of the fully-discrete scheme are obtained. Finally, several numerical results are given to confirm the theoretical results.

Cushing's disease (CD) is a rare disease that occurs in 1.2–1.4 persons per million population per year. Recurrence prediction after transsphenoidal surgery (TSS) is important for determining individual treatment and follow-up strategies. Between 2000 and 2017, 354 CD patients with initial postoperative remission and long-term follow-up data were enrolled from Peking union medical college hospital (PUMCH) to predict recurrence, and PUMCH is one of the largest CD treatment centers in the world. We first investigated the effect of a factorization machine (FM)-based neural network to predict recurrence after TSS for CD. This method could automatically reduce a portion of the cross-feature selection work with acceptable parameters. We conducted a performance comparison of various algorithms on the collected dataset. To address the lack of interpretability of neural network models, we also used the local interpretable model-agnostic explanations approach, which provides an explanation in the form of relevant features of the predicted results by approximating the model behavior of the variables in a local manner. Compared with existing methods, the DeepFM model obtained the highest AUC value (0.869) and the lowest log loss value (0.256). According to the importance of each feature, three top features for the DeepFM model were postoperative morning adrenocorticotropic hormone level, age, and postoperative morning serum cortisol nadir. In the post hoc explanation phase, the above-mentioned importance-leading features made a great contribution to the prediction probability. The results showed that deep learning-based models could better aid neurosurgeons in recurrence prediction after TTS for patients with CD, and could contribute to determining individual treatment strategies.

Quantitative real time PCR (qPCR)is used for pertussis diagnosis. The positive rate of qPCR is generally much higher than that of bacterial culture, which may cause confusion. The current study utilized the 16S ribosomal RNA (16S rRNA) sequencing to assess the correlation between conventional culture and qPCR and to explore the value of 16S rRNA in diagnosing pertussis. Nasopharyngeal swabs, collected from 102 children meeting clinical diagnostic criteria for pertussis, were subjected to Bordetella pertussis culture and qPCR. Bioinformatic microbiota analysis was based on 16S rRNA V3-V4 gene sequencing. Among 102 samples, 14 (13.7%) were culture-positive for Bordetella pertussis, while 61 (59.8%) were qPCR positive. Genus Bordetella was identified in 68 (66.7%) samples via 16S rRNA sequencing. When the relative abundance of Bordetella genus exceeded 0.70%, both qPCR and culture results were positive. Samples with a relative abundance of less than 0.20% exhibited positive qPCR and negative culture results. Samples with a low Bordetella abundance are the key factors underlying poor correlation between culture and qPCR results in laboratory tests.

The solution of the nonlinear subdiffusion equation has the initial layer and its initial energy may decay very fast. Therefore, it is important to investigate the evolution of the solution at the beginning. In the paper, a transformed L1 scheme is proposed to capture the initial dramatic evolution. It is proved that the temporal error of the new method is $${\mathcal {O}}(\tau ^{2-\alpha })$$ , where $$\tau $$ is the temporal stepsize and $$0

To graft epoxy and ester functional groups onto cellulose nanofibrils (CNFs) and to overcome their poor hydrophobicity, we studied the modification of CNFs using graft copolymerization wi ...

A Newton linearized Galerkin finite element method is proposed to solve nonlinear time fractional parabolic problems with non-smooth solutions in time direction. Iterative processes or corrected schemes become dispensable by the use of the Newton linearized method and graded meshes in the temporal direction. The optimal error estimate in the $$L^2$$ -norm is obtained without any time step restrictions dependent on the spatial mesh size. Such unconditional convergence results are proved by including the initial time singularity into concern, while previous unconditional convergent results always require continuity and boundedness of the temporal derivative of the exact solution. Numerical experiments are conducted to confirm the theoretical results.

Betulin, a natural compound extractable from the outer bark of birch, can be used to improve the properties of cellulosic textile fibres. Herein, oxidation was performed to prepare carboxyl-functionalized cellulose, which was subsequently covalently attached by betulin through esterification. The surface-modified cellulosic textile fibres showed a substantially improved hydrophobicity, as indicated by a water contact angle of 136°. Moreover, the material showed excellent antibacterial properties, as indicated by over 99% bacterial removal and growth inhibition, in both Gram-positive and Gram-negative bacterial assays. The method of surface-modification of the cellulosic materials adapted in this study is simple and, to the best of our knowledge, has not been carried out before. The results of this study prove that betulin, a side-stream product produced by forest industry, could be used in value-added applications, such as for preparing functional materials. Additionally, this modification route can be envisaged to be applied to other cellulose sources (e.g., microfibrillated cellulose) to achieve the goal of functionalization.

We use the scalar auxiliary variable (SAV) reformulation of the nonlinear Schrodinger (NLS) equation to construct structure-preserving SAV–Gauss methods for the NLS equation, namely $$L^2$$ -conservative methods satisfying a discrete analogue of the energy (the Hamiltonian) conservation of the equation. This is in contrast to Gauss methods for the standard form of the NLS equation that are $$L^2$$ -conservative but not energy-conservative. We also discuss efficient linearizations of the new methods and their conservation properties.

Background The initialization of the neonatal gut microbiota (GM) is affected by diverse factors and is associated with infant development and health outcomes. Methods In this study, we collected 207 faecal samples from 41 infants at 6 time points (1, 3, and 7 days and 1, 3, and 6 months after birth). The infants were assigned to four groups according to delivery mode (caesarean section (CS) or vaginal delivery (VD)) and feeding pattern (breastfeeding or formula milk). Results The meconium bacterial diversity was slightly higher in CS than in VD. Three GM patterns were identified, including Escherichia/Shigella-Streptococcus-dominated, Bifidobacterium-Escherichia/Shigella-dominated and Bifidobacterium-dominated patterns, and they gradually changed over time. In CS infants, Bifidobacterium was less abundant, and the delay in GM establishment could be partially restored by breastfeeding. The frequency of respiratory tract infection and diarrhoea consequently decreased. Conclusion This study fills some gaps in the understanding of the restoration of the GM in CS towards that in VD.

The solutions of the nonlinear time fractional parabolic problems usually undergo dramatic changes at the beginning. In order to overcome the initial singularity, the temporal discretization is done by using the Alikhanov schemes on the nonuniform meshes. And the spatial discretization is achieved by using the finite element methods. The optimal error estimates of the fully discrete schemes hold without certain time-step restrictions dependent on the spatial mesh sizes. Such unconditionally optimal convergent results are proved by taking the global behavior of the analytical solutions into account. Numerical results are presented to confirm the theoretical findings.

A key issue in developing efficient numerical schemes for nonlinear wave equations is the energy-conserving. Most existing schemes of the energy-conserving are fully implicit and the schemes require an extra iteration at each time step and considerable computational cost for a long time simulation, while the widely-used q-stage (implicit) Gauss scheme (method) only preserves polynomial Hamiltonians up to degree 2q. In this paper, we present a family of linearly implicit and high-order energy-conserving schemes for solving nonlinear wave equations. The construction of schemes is based on recently-developed scalar auxiliary variable technique with a combination of classical high-order Gauss methods and extrapolation approximation. We prove that the proposed schemes are unconditionally energy-conserved for a general nonlinear wave equation. Numerical results are given to show the energy-conserving and the effectiveness of schemes.

Background Cryptosporidium spp. and Giardia duodenalis are major intestinal pathogens that can cause diarrheal diseases in humans, especially children. Enterocytozoon bieneusi is another parasite which can cause gastrointestinal tract disorders, with diarrhea being the main clinical symptom. However, few genetic studies of these parasites in pediatric inpatients in China have been published. Methods To assess the genetic characteristics and epidemiological status of these parasites, a total of 2284 fecal samples were collected from children in the pediatric departments of three hospitals in Zhengzhou, central China, and screened for these protozoans with PCR, based on the small subunit ribosomal RNA (SSU rRNA) genes of Cryptosporidium spp. and G. duodenalis and the internal transcribed spacer (ITS) of E. bieneusi. Results Six (0.26%), 14 (0.61%), and 27 (1.18%) of the samples were positive for Cryptosporidium spp., G. duodenalis and E. bieneusi, respectively. Of the 12 successfully sequenced G. duodenalis isolates, four were identified as assemblage A and eight as assemblage B. In subtype and multilocus genotype (MLG) analyses, C. parvum IIdA19G1 (n = 4) and two novel G. duodenalis MLGs belonging to subassemblage AII (n = 3) and BIV (n = 5) were successfully identified. The E. bieneusi isolates included genotypes D (n = 17), J (n = 2), PigEBITS7 (n = 1), BEB6 (n = 1), and CM8 (n = 1). This is the first report of C. parvum subtype IIdA19G1 in HIV-negative children and E. bieneusi genotype CM8 in humans. Conclusions The dominance of zoonotic C. parvum subtype IIdA19G1 indicates that this parasite is turning into zoonotic origin from human-to-human transmission. The phylogenetic analysis also revealed the zoonotic origins and anthroponotic transmission potential of G. duodenalis and E. bieneusi, suggesting more efforts must be made to minimize the threat these pathogens pose to public health.

SCNT technology has been successfully used to clone a variety of mammals, but the cloning efficiency is very low. This low efficiency is likely due to the incomplete reprogramming of SCNT embryos. Histone modification and DNA methylation may participate in these events. Thus, it would be interesting to attempt to improve the efficiency of SCNT by using a HDACi VPA. In order to guarantee the effect of VPA and reduce its cytotoxicity, a comprehensive analysis of the cell proliferation and histone modification was performed. The results showed that 0.5 and 1 mM VPA treatment for 24 h were the optimal condition. According to the results, H3K4me3 was increased in 0.5 and 1 mM VPA groups, whereas H3K9me2 was significantly decreased. These are the signals of gene-activation. In addition, VPA treatment led to the overexpression of Oct4 and Nanog. These indicated that VPA-treated cells had similar patterns of histone to zygotic embryos, and may be more favorable for reprograming. A total of 833 cloned embryos were produced from the experimental replicates of VPA-treated donor cells. In 1 mM treatment group, the blastocyst rates were significantly increased compared with control. At the same time, our findings demonstrated the interrelation between DNA methylation and histone modifications.

Achieving satisfactory reconstruction of bone remains an important goal in orthopedic and dental conditions such as bone trauma, osteoporosis, arthritis, osteonecrosis, and periodontitis. Appropriate temporal and spatial differentiation of mesenchymal stem cells (MSCs) is essential for postnatal bone regeneration. Additionally, an acute inflammatory response is crucial at the onset of bone repair, while an adaptive immune response has important implications during late bone remodeling. Various reports have indicated bidirectional interactions between MSCs and inflammatory cells or molecules. For example, inflammatory cells can recruit MSCs, direct their migration and differentiation, so as to exert anabolic effects on bone repair. Furthermore, both pro-inflammatory and anti-inflammatory cytokines can regulate MSCs properties and subsequent bone regeneration. MSCs have demonstrated highly immunosuppressive functions, such as inhibiting the differentiation of monocytes/hematopoietic precursors and suppressing the secretion of pro-inflammatory cytokines. This review emphasizes the important interactions between inflammatory stimuli, MSCs, and bone regeneration as well as the underlying regulatory mechanisms. Better understanding of these principles will provide new opportunities for promoting bone regeneration and the treatment of bone loss associated with immunological diseases.

Betulin is a naturally abundant and hydrophobic compound in the outer bark of birch and can readily be obtained by solvent extraction. Here, solutions of betulin were used to treat cotton fabrics a ...

This paper is concerned with unconditionally optimal error estimates of linearized Galerkin finite element methods to numerically solve some multi-dimensional fractional reaction–subdiffusion equations, while the classical analysis for numerical approximation of multi-dimensional nonlinear parabolic problems usually require a restriction on the time-step, which is dependent on the spatial grid size. To obtain the unconditionally optimal error estimates, the key point is to obtain the boundedness of numerical solutions in the $$L^\infty $$ -norm. For this, we introduce a time-discrete elliptic equation, construct an energy function for the nonlocal problem, and handle the error summation properly. Compared with integer-order nonlinear problems, the nonlocal convolution in the time fractional derivative causes much difficulties in developing and analyzing numerical schemes. Numerical examples are given to validate our theoretical results.

This paper presents a turning strategy of snake-like robot based on Serpenoid curve. By using four criteria to judge turning control approaches on the basis of serpenoid curve, three commonly used turning control approaches (i.e., central value modulation method, phase modulation method and amplitude modulation method) are first analyzed. Then the tangent control approach and the combination control approach are used to solve turning challenges such as deficiency in maintaining the serpenoid curve, limited turning angle, discontinuous joint angle, large turning radius and large amplitude of joint angle variation during and after turning. These approaches were tested and verified by using a snake-like robot prototype. It is found that the proposed approaches work well for the turning locomotion of the snake-like robot. The present turning strategy provides an important alternative for locomotion control of the snake-like robot.

In this work, we investigate effects of scanning speed (800 mm s−1, 900 mm s−1, 1083 mm s−1) on in vitro biocompatibility of 316L stainless steel (SS) parts elaborated by selective laser melting (SLM). Cytotoxicity assay and hemolytic test are adopted to assess the in vitro biocompatibility of 316L SS parts. The experimental results show that the scanning speed has strong effects on the in vitro cytotoxicity of 316L SS parts and no significant effect on the hemolysis. In order to investigate the mechanism of effects of scanning speed on in vitro biocompatibility, microstructures of 316L SS parts via SLM are obtained by scanning electron microscopy (SEM). The finer grain and less defects lead to better biocompatibility, due to the increase of corrosion resistance and decrease of toxicity ions release. In cases of 900 and 1083 mm s−1, finer microstructures can be observed and the minimum manufacturing defects are formed on 316L SS parts under 900 mm s−1 scanning speed. The results indicate that by changing the scanning speed, the microstructures, in terms of the quality of grain and the mount of defects, can be adjusted; as a result, controllable biocompatibility of 316L SS parts via SLM can be achieved.

In this paper, we present unconditionally optimal error estimates of linearized Crank–Nicolson Galerkin finite element methods for a strongly nonlinear parabolic system in $$\mathbb {R}^d\ (d=2,3)$$ . However, all previous works required certain time-step conditions that were dependent on the spatial mesh size. In order to overcome several entitative difficulties caused by the strong nonlinearity of the system, the proof takes two steps. First, by using a temporal-spatial error splitting argument and a new technique, optimal $$L^2$$ error estimates of the numerical schemes can be obtained under the condition $$\tau \ge h$$ , where $$\tau $$ denotes the time-step size and h is the spatial mesh size. Second, we obtain the boundedness of numerical solutions by mathematical induction and inverse inequality when $$\tau \le h$$ . Then, optimal $$L^2$$ and $$H^1$$ error estimates are proved in a different way for such case. Numerical results are given to illustrate our theoretical analyses.

Soil microbial communities influence nutrient cycling, chemistry and structure of soil, and plant productivity. In turn, agronomic practices such as fertilization and crop rotation alter soil physical and chemical properties and consequently soil microbiomes. Understanding the long-term effects of agronomic practices on soil microbiomes is essential for improving agronomic practices to optimize these microbial communities for agricultural sustainability. We examine the composition and substrate-utilization profiles of microbial communities at the Morrow Plots in Illinois. Microbial community composition is assessed with 16S rRNA gene sequencing and subsequent bioinformatic analyses. Community- level substrate utilization is characterized with the BIOLOG EcoPlate. Fertilizer and rotation treatments significantly affected microbial community structure, while substrate utilization was affected by fertilizer, but not crop-rotation treatments. Differences in relative abundance and occurrence of bacterial taxa found in fertilizer treatments can explain the observed differences in community level substrate utilization. Long-term fertilization and crop-rotation treatments affect soil microbial community composition and physiology, specifically through chronic nutrient limitation, long-term influx of microbes and organic matter via manure application, as well as through changes in soil chemistry. Relatively greater abundance of Koribacteraceae and Solibacterales taxa in soils might prove useful as indicators of soil degradation.

The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and investigate their relationships with clinical indicators, 1,914 Chinese adults were enrolled for 16S rRNA gene sequencing in this retrospective study. Based on GM composition, Random forest classifiers were constructed to screen the obesity patients with (Group OA) or without metabolic diseases (Group O) from healthy individuals (Group H), and high accuracies were observed for the discrimination of Group O and Group OA (areas under the receiver operating curve (AUC) equal to 0.68 and 0.76, respectively). Furthermore, six GM markers were shared by obesity patients with various metabolic disorders (Bacteroides, Parabacteroides, Blautia, Alistipes, Romboutsia and Roseburia). As for the discrimination with Group O, Group OA exhibited low accuracy (AUC = 0.57). Nonetheless, GM classifications to distinguish between Group O and the obese patients with specific metabolic abnormalities were not accurate (AUC values from 0.59 to 0.66). Common biomarkers were identified for the obesity patients with high uric acid, high serum lipids and high blood pressure, such as Clostridium XIVa, Bacteroides and Roseburia. A total of 20 genera were associated with multiple significant clinical indicators. For example, Blautia, Romboutsia, Ruminococcus2, Clostridium sensu stricto and Dorea were positively correlated with indicators of bodyweight (including waistline and body mass index) and serum lipids (including low density lipoprotein, triglyceride and total cholesterol). In contrast, the aforementioned clinical indicators were negatively associated with Bacteroides, Roseburia, Butyricicoccus, Alistipes, Parasutterella, Parabacteroides and Clostridium IV. Generally, these biomarkers hold the potential to predict obesity-related metabolic abnormalities, and interventions based on these biomarkers might be beneficial to weight loss and metabolic risk improvement.

Background Microglia are important for secreting chemical mediators of inflammatory responses in the central nervous system. Interleukin (IL)-10 and IL-1β secreted by glial cells support neuronal functions, but the related mechanisms remain vague. Our goal was to demonstrate the efficacy of IL-10 in suppressing IL-1β and in inflammasome activation in mice with epileptic seizure based on an epileptic-seizure mouse model. Methods In this study, mice in which epileptic seizures were induced by administering picrotoxin (PTX) were used as a case group, and mice injected with saline were employed as the control group. The expression of nucleic acids, cytokines, or signaling pathways was detected by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), flow cytometry, and Western blotting. Results Our results demonstrated that IL-10 inhibits IL-1β production through two distinct mechanisms: (1) Treatment with lipopolysaccharides (LPS) results in IL-10 overexpression in microglia and reduced NLRP3 inflammasome activity, thus inhibiting caspase-1-related IL-1β maturation; (2) next, autocrine IL-10 was found to subsequently promote signal transducer and activator of transcription-3 (STAT-3), reducing amounts of pro-IL-1β. Conclusions Our results indicate that IL-10 is potentially effective in the treatment of inflammation encephalopathy, and suggest the potential usefulness of IL-10 for treating autoimmune or inflammatory ailments. Electronic supplementary material The online version of this article (10.1186/s12974-019-1452-1) contains supplementary material, which is available to authorized users.

Optical interferometry has enabled quantification of the spatial and temporal correlations of electromagnetic fields, which laid the foundations for the theory of optical coherence. Despite significant advances in fundamental theories and applications, the measurement of nanoscale coherence lengths for highly incoherent optical fields has remained elusive. Here, we employ plasmonic interferometry (that is, optical interferometry with surface plasmons) to characterize the spatial degree of coherence of light beams down to subwavelength scales, with measured coherence lengths as low as ∼330 nm for an incident wavelength of 500 nm. Furthermore, we demonstrate a compact coherence meter that integrates this method with an image sensor. Precise determination of spatial coherence can advance high-resolution imaging and tomographic schemes, and provide an experimental platform for the development and testing of optical coherence theories at the nanoscale. Surface plasmon interferometry is used to measure the spatial coherence at subwavelength scales.

Lipopolysaccharide (LPS)-induced osteoblast apoptosis is a prominent factor to the defect in periodontal tissue repair in periodontal disease. LPS challenge contributes to the production of reactive oxygen species (ROS) in periodontitis, and peroxiredoxin 1 (Prx1) is an antioxidant protein that protect cells against oxidative damage from ROS. Without LPS stimulation, apoptotic rates were higher in both Prx1 knockout (Prx1KO) and Prx1 overexpression (Prx1OE) cells compared with wild type. After LPS stimulation, intracellular ROS in Prx1KO cells showed the highest level and Prx1OE cells showed the least. Treatment with LPS significantly elevated the expression of Bax, Cyto-c, and caspase 3 in Prx1KO cells compared with wild type, although this could be completely abolished by NAC. In Prx1OE cells, the expression and activation of ASK1 were significantly increased, and this was slightly reduced by LPS stimulation. NQDI-1 completely abolished the increased phosphorylation of JNK and p38 and the expression of caspase 3 in LPS-stimulated cells. These results indicate that Prx1 eliminates intracellular ROS and exhibits a cytoprotective role in LPS-induced apoptosis. However, under physiological conditions, Prx1 overexpression acts as a H2O2 messenger, triggering the expression of ASK1 and its downstream cascades.

Multiple sulfur isotopes (32S, 33S, 34S, 36S) and oxygen isotopes (16O, 18O) in Beijing aerosols were measured with MAT-253 isotope mass spectrometer. The δ 34S values of Beijing aerosol samples range from 1.68‰ to 12.57‰ with an average value of 5.86‰, indicating that the major sulfur source is from direct emission during coal combustion. The δ 18O values vary from -5.29‰ to 9.02‰ with an average value of 5.17‰, revealing that the sulfate in Beijing aerosols is mainly composed of the secondary sulfate. The main heterogeneous oxidation of SO2 in atmosphere is related to H2O2 in July and August, whereas H2O2 oxidation and Fe3+ catalytic oxidation with SO2 exist simultaneously in September and October. Remarkable sulfur isotope mass-independent fractionation effect is found in Beijing aerosols, which is commonly attributed to the photochemical oxidation of SO2 in the stratosphere. In addition, thermochemical reactions of sulfur-bearing compounds might be also a source of sulfur isotope anomalies based on the correlation between Δ33S and CAPE.

The worldwide emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis threatens to make this disease incurable. Drug resistance mechanisms are only partially understood, and whether the current understanding of the genetic basis of drug resistance in M. tuberculosis is sufficiently comprehensive remains unclear. Here we sequenced and analyzed 161 isolates with a range of drug resistance profiles, discovering 72 new genes, 28 intergenic regions (IGRs), 11 nonsynonymous SNPs and 10 IGR SNPs with strong, consistent associations with drug resistance. On the basis of our examination of the dN/dS ratios of nonsynonymous to synonymous SNPs among the isolates, we suggest that the drug resistance-associated genes identified here likely contain essentially all the nonsynonymous SNPs that have arisen as a result of drug pressure in these isolates and should thus represent a near-complete set of drug resistance-associated genes for these isolates and antibiotics. Our work indicates that the genetic basis of drug resistance is more complex than previously anticipated and provides a strong foundation for elucidating unknown drug resistance mechanisms.

In 2011, Shiga toxin-producing Escherichia coli O104:H4 resulted in a large outbreak of bloody diarrhea and hemolytic uremic syndrome (HUS) in Germany and 15 other countries in Europe and North America. This event raised a serious public health crisis and caused more than two billion US dollars in economic losses. In this review, we describe the classification of E. coli , the Germany outbreak, and the characteristics and epidemical source-tracing of the causative agent. We also discuss the genomics analysis of the outbreak organism and propose an open-source genomics analysis as a new strategy in combating the emerging infectious diseases.

Falls are common in older adults and result in adverse outcomes. Impaired mobility and poor muscle strength have been consistently identified as the main contributors to falls. We choose three easy-to-perform tests (i.e. Timed Up and Go test (TUGT), walking speed (WS) and grip strength (GS)) in order to assess mobility and muscle strength to further define their relationship with falls. This study is cross-sectional, consisting of 1092 residents over 60-year-old; 589 were female. 204 (18.68%) participants reported falling at least once in the past year. It was found that, of the three tests evaluated independently, a TUGT 0.3816 was most correlated with less possibility of falls. The combination of a better TUGT performance, a stronger GS and a slower WS is the most strongly correlated with less possibility of falls.

High-speed control of polarization may lead to ultrafast modulators and help explore polarization-dependent ultrafast dynamics in matter. Now, femtosecond polarization switching is realized through intraband optical excitation in an ultrathin semiconductor layer.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme for heme catabolism and iron production, its role in intracerebral hemorrhage (ICH) is controversial. The study was to investigate correlations between brain oxidative injury and HO-1 after experimental ICH.Sprague-Dawley rats received intra-striatal infusions of 100 μl autologous whole blood as ICH models. HO-1 were examined by immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) analysis. Brain oxidative stress was quantitated by malondialdehyde (MDA); antioxidation were measured by copper-zinc superoxide dismutase (Cu/Zn-SOD) activity using RT-PCR assay.The expression of the HO-1 upregulated and reached its peak at days 3 and 7 after ICH (P 0.01). There was a significant increase of MDA and a top at 3-day post-ICH (P 0.01); Cu/Zn-SOD was upregulated post-ICH and reached the top at day 7 (P 0.001); HO-1 was correlated significantly with brain MDA content at days 7 and 14 following ICH (r = 0.435-0.501, P 0.001) but there is no definite correlation between them on 1 to 3 days (P 0.05); conversely, HO-1 was correlated significantly with Cu/Zn-SOD on 1 to 3 days after ICH (r = 0.433-0.621, P 0.001) but there is no definite correlation between them at days 7 and 14 (P 0.05).HO-1 has both antioxidant and prooxidant properties in ICH. The early upregulation of HO-1 possibly fit with the events and be protective against oxidative stress, whereas its overexpression in the late stages may result in its dysfunction and be toxic. So it should be prudent to intervene ICH with the inhibitor/activator of HO-1.

Udgivelsesdato: 2010-Jan Here we integrate the de novo assembly of an Asian and an African genome with the NCBI reference human genome, as a step toward constructing the human pan-genome. We identified approximately 5 Mb of novel sequences not present in the reference genome in each of these assemblies. Most novel sequences are individual or population specific, as revealed by their comparison to all available human DNA sequence and by PCR validation using the human genome diversity cell line panel. We found novel sequences present in patterns consistent with known human migration paths. Cross-species conservation analysis of predicted genes indicated that the novel sequences contain potentially functional coding regions. We estimate that a complete human pan-genome would contain approximately 19-40 Mb of novel sequence not present in the extant reference genome. The extensive amount of novel sequence contributing to the genetic variation of the pan-genome indicates the importance of using complete genome sequencing and de novo assembly.

Background Maternal diet during pregnancy can modulate skeletal muscle development of the offspring. Previous studies in pigs have indicated that a fat supplemented diet during pregnancy can improve piglet outcome, however, this is in contrast to human studies suggesting adverse effects of saturated fats during pregnancy. This study aimed to investigate the impact of a fat supplemented (palm oil) “high fat” diet on skeletal muscle development in a porcine model. Histological and metabolic features of the biceps femoris muscle obtained from 7-day-old piglets born to sows assigned to either a commercial (C, n = 7) or to an isocaloric fat supplementation diet (“high fat” HF, n = 7) during pregnancy were assessed. Results Offspring exposed to a maternal HF diet demonstrated enhanced muscular development, reflected by an increase in fractional growth rate, rise in myofibre cross-sectional area, increased storage of glycogen and reduction in lipid staining of myofibres. Although both groups had similar intramuscular protein and triglyceride concentrations, the offspring born to HF mothers had a higher proportion of arachidonic acid (C20:4n6) and a reduction in α-linolenic acid (C18:3n3) compared to C group offspring. The HF group muscle also exhibited a higher ratio of C20:3n6 to C20:4n6 and total n-6 to n-3 in conjunction with up-regulation of genes associated with free fatty acid uptake and biogenesis. Conclusion In conclusion, a HF gestational diet accelerates the maturation of offspring biceps femoris muscle, reflected in increased glycolytic metabolism and fibre cross sectional area, differences accompanied with a potential resetting of myofibre nutrient uptake.

Thalassemia major is an inherited hemoglobin disorder characterized by chronic anemia and iron overload due to transfusion therapy and gastrointestinal absorption. Iron overload causes severe endocrine complications in patients with multi-transfused thalassaemia major. Endocrine complications includes short stature, acquired hypothyroidism and hypoparathyroidism, hypogonadism, glucose intolerance and diabetes mellitus.