Search

Abstract Autoreactive CD4+ T helper cells are critical players that orchestrate the immune response both in multiple sclerosis (MS) and in other neuroinflammatory autoimmune diseases. Ubiquitination is a posttranslational protein modification involved in regulating a variety of cellular processes, including CD4+ T cell differentiation and function. However, only a limited number of E3 ubiquitin ligases have been characterized in terms of their biological functions, particularly in CD4+ T cell differentiation and function. In this study, we found that the RING finger protein 213 (RNF213) specifically promoted regulatory T (Treg) cell differentiation in CD4+ T cells and attenuated autoimmune disease development in an FOXO1-dependent manner. Mechanistically, RNF213 interacts with Forkhead Box Protein O1 (FOXO1) and promotes nuclear translocation of FOXO1 by K63-linked ubiquitination. Notably, RNF213 expression in CD4+ T cells was induced by IFN-β and exerts a crucial role in the therapeutic efficacy of IFN-β for MS. Together, our study findings collectively emphasize the pivotal role of RNF213 in modulating adaptive immune responses. RNF213 holds potential as a promising therapeutic target for addressing disorders associated with Treg cells.

ObjectiveNurses are key in administering oxygen therapy and managing its potential adverse effects in medical settings. This study aimed to investigate the knowledge, attitudes, and practices (KAP) regarding low-flow oxygen therapy and humidification among nurses.MethodsThis cross-sectional study was conducted from January 2024 to March 2024 at Shanghai Xuhui Central Hospital. Demographic data and KAP scores were collected through questionnaires.ResultA total of 243 valid questionnaires were collected. Among them, 228 (93.8%) were female, and 93 (38.3%) had been working for more than 10 years. The mean scores for knowledge, attitudes, and practices were 11.11 ± 4.30 (Ranging 0–18), 29.14 ± 3.41 (Ranging 7–35), and 28.07 ± 4.73 (Ranging 7–35), respectively. Multivariate logistic regression confirmed that knowledge (OR = 1.302, 95% CI: [1.167–1.453], p

Abstract Background The pathway involving PTEN-induced putative kinase 1 (PINK1) and PARKIN plays a crucial role in mitophagy, a process activated by artesunate (ART). We propose that patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis exhibit insufficient mitophagy, and ART enhances mitophagy via the PINK1/PARKIN pathway, thereby providing neuroprotection. Methods Adult female mice aged 8–10 weeks were selected to create a passive transfer model of anti-NMDAR encephalitis. We conducted behavioral tests on these mice within a set timeframe. Techniques such as immunohistochemistry, immunofluorescence, and western blotting were employed to assess markers including PINK1, PARKIN, LC3B, p62, caspase3, and cleaved caspase3. The TUNEL assay was utilized to detect neuronal apoptosis, while transmission electron microscopy (TEM) was used to examine mitochondrial autophagosomes. Primary hippocampal neurons were cultured, treated, and then analyzed through immunofluorescence for mtDNA, mtROS, TMRM. Results In comparison to the control group, mitophagy levels in the experimental group were not significantly altered, yet there was a notable increase in apoptotic neurons. Furthermore, markers indicative of mitochondrial leakage and damage were found to be elevated in the experimental group compared to the control group, but these markers showed improvement following ART treatment. ART was effective in activating the PINK1/PARKIN pathway, enhancing mitophagy, and diminishing neuronal apoptosis. Behavioral assessments revealed that ART ameliorated symptoms in mice with anti-NMDAR encephalitis in the passive transfer model (PTM). The knockdown of PINK1 led to a reduction in mitophagy levels, and subsequent ART intervention did not alleviate symptoms in the anti-NMDAR encephalitis PTM mice, indicating that ART’s therapeutic efficacy is mediated through the activation of the PINK1/PARKIN pathway. Conclusions At the onset of anti-NMDAR encephalitis, mitochondrial damage is observed; however, this damage is mitigated by the activation of mitophagy via the PINK1/PARKIN pathway. This regulatory feedback mechanism facilitates the removal of damaged mitochondria, prevents neuronal apoptosis, and consequently safeguards neural tissue. ART activates the PINK1/PARKIN pathway to enhance mitophagy, thereby exerting neuroprotective effects and may achieve therapeutic goals in treating anti-NMDAR encephalitis.

Osteoarthritis (OA) is a prevalent cause of joint algesia, loss of function, and disability in adults, with cartilage injury being its core pathological manifestation. Since cartilage damage is non-renewable, the treatment outcome in the middle and late stages of OA is unsatisfactory, which can be minimized by changing lifestyle and other treatment modalities if diagnosed and managed in the early stages, indicating the importance of early diagnosis and monitoring of cartilage injury. Ultrasound technology has been used for timely diagnosis and even cartilage injury treatment, which is convenient and safe for the patient owing to no radiation exposure. Studies have demonstrated the effectiveness of ultrasound and its various quantitative ultrasound parameters, like ultrasound roughness index (URI), reflection coefficient (R), apparent integrated backscatter (AIB), thickness, and ultrasound elastography, in the early and accurate assessment of OA cartilage pathological changes, including surface and internal tissue, hardness, and thickness. Although many challenges are faced in the clinical application of this technology in diagnosis, ultrasound and ultrasound-assisted techniques offer a lot of promise for detecting early cartilage damage in OA. In this review, we have discussed the evaluation of ultrasonic cartilage quantitative parameters for early pathological cartilage changes.

As a non-renewable resource, oil faces increasing demand, and the remaining oil recovery rates in existing oil fields still require improvement. The primary objective of this study is to investigate the impact of pore structure parameters on the distribution and recovery of residual oil after polymer flooding by constructing a digital pore network model. Using this model, the study visualizes the post-flooding state of the model with 3DMAX-9.0 software and employs a range of simulation methods, including a detailed analysis of the pore size, coordination number, pore–throat ratio, and wettability, to quantitatively assess how these parameters affect the residual oil distribution and recovery. The research shows that the change in the distribution of pore sizes leads to a decrease in cluster-shaped residual oil and an increase in columnar residual oil. An increase in the coordination number increases the core permeability and reduces the residual oil; for example, when the coordination number increases from 4.3 to 6, the polymer flooding recovery rate increases from 24.57% to 30.44%. An increase in the pore–throat ratio reduces the permeability and causes more residual oil to remain in the throat; for example, when the pore–throat ratio increases from 3.2 to 6.3, the total recovery rate decreases from 74.34% to 63.72%. When the wettability changes from oil-wet to water-wet, the type of residual oil gradually changes from the difficult-to-drive-out columnar and film-shaped to the more easily recoverable cluster-shaped; for example, when the proportion of water-wet throats increases from 0.1:0.9 to 0.6:0.4, the water flooding recovery rate increases from 35.63% to 51.35%. Both qualitative and quantitative results suggest that the digital pore network model developed in this study effectively predicts the residual oil distribution under different pore structures and provides a crucial basis for optimizing residual oil recovery strategies.

Osteoarthritis (OA) is distinguished by pathological alterations in the synovial membrane, articular cartilage, and subchondral bone, resulting in physical symptoms such as pain, deformity, and impaired mobility. Numerous research studies have validated the effectiveness of low-intensity pulsed ultrasound (LIPUS) in OA treatment. The periodic mechanical waves generated by LIPUS can mitigate cellular ischemia and hypoxia, induce vibration and collision, produce notable thermal and non-thermal effects, alter cellular metabolism, expedite tissue repair, improve nutrient delivery, and accelerate the healing process of damaged tissues. The efficacy and specific mechanism of LIPUS is currently under investigation. This review provides an overview of LIPUS’s potential role in the treatment of OA, considering various perspectives such as the synovial membrane, cartilage, subchondral bone, and tissue engineering. It aims to facilitate interdisciplinary scientific research and further exploration of LIPUS as a complementary technique to existing methods or surgery. Ongoing research is focused on determining the optimal dosage, frequency, timing, and treatment strategy of LIPUS for OA. Additional research is required to clarify the precise mechanism of action and potential impacts on cellular, animal, and human systems prior to its integration into therapeutic applications.

Purpose: Spinal multiple myeloma (MM) and metastases are two common cancer types with similar imaging characteristics, for which differential diagnosis is needed to ensure precision therapy. The aim of this study is to establish radiomics models for effective differentiation between them. Methods: Enrolled in this study were 263 patients from two medical institutions, including 127 with spinal MM and 136 with spinal metastases. Of them, 210 patients from institution I were used as the internal training cohort and 53 patients from Institution II were used as the external validation cohort. Contrast-enhanced T1-weighted imaging (CET1) and T2-weighted imaging (T2WI) sequences were collected and reviewed. Based on the 1037 radiomics features extracted from both CET1 and T2WI images, Logistic Regression (LR), AdaBoost (AB), Support Vector Machines (SVM), Random Forest (RF), and multiple kernel learning based SVM (MKL-SVM) were constructed. Hyper-parameters were tuned by five-fold cross-validation. The diagnostic efficiency among different radiomics models was compared by accuracy (ACC), sensitivity (SEN), specificity (SPE), area under the ROC curve (AUC), YI, positive predictive value (PPV), negative predictive value (NPY), and F1-score. Results: Based on single-sequence, the RF model outperformed all other models. All models based on T2WI images performed better than those based on CET1. The efficiency of all models was boosted by incorporating CET1 and T2WI sequences, and the MKL-SVM model achieved the best performance with ACC, AUC, and F1-score of 0.862, 0.870, and 0.874, respectively. Conclusions: The radiomics models constructed based on MRI achieved satisfactory diagnostic performance for differentiation of spinal MM and metastases, demonstrating broad application prospects for individualized diagnosis and treatment.

Recent studies have demonstrated that ferroptosis, a novel form of nonapoptotic regulated cell death plays an important role in doxorubicin (DOX)-induced cardiotoxicity (DoIC). Hydrogen sulfide (H2S) is emerging as the third important gaseous mediator in cardiovascular system. However, whether H2S has an effect on DOX-induced ferroptosis remains unknown. Here, we found that DOX not only triggered cardiomyocyte ferroptosis but also significantly inhibited the synthesis of endogenous H2S in the murine model of chronic DoIC. Application of NaHS, an H2S donor obviously activated the SLC7A11/GSH/GPx4 antioxidant pathway and thus alleviated DOX-induced ferroptosis and cardiac injury in mice. In contrast, cardiac-specific knockout of cystathionine γ-lyase gene (Cse) in mice (Csef/f/Cre+) to abolish the cardiac synthesis of endogenous H2S evidently exacerbated DOX-induced ferroptosis and cardiac dysfunction. A further suppression of SLC7A11/GSH/GPx4 pathway was obtained in Csef/f/Cre+ mice with DoIC, as compared to Csef/f/Cre− mice with DoIC. The aggravation caused by cardiac-specific Cse deficiency was remarkably rescued by exogenous supplementation of NaHS. Moreover, in DOX-stimulated H9c2 cardiomyocytes, pretreatment with NaHS dose-dependently enhanced the activity of SLC7A11/GSH/GPx4 pathway and subsequently mitigated ferroptosis and mitochondrial impairment. On the contrary, transfection with Cse siRNA in DOX-stimulated H9c2 cardiomyocytes markedly inhibited SLC7A11/GSH/GPx4 pathway, thus leading to aggravated ferroptosis and more damage to mitochondrial structure and function. In addition, the protective effect of NaHS on DOX-induced ferroptosis was closely related to the S-sulfhydrated Keap1, which in turn promoted nuclear translocation of Nrf2 and the transcription of SLC7A11 and GPx4. In conclusion, our findings suggest that H2S may exert protective effect on DoIC by inhibiting DOX-induced ferroptosis via Keap1/Nrf2-dependent SLC7A11/GSH/GPx4 antioxidant pathway.

Abstract Purpose This study aimed to develop and validate a model based on biparametric magnetic resonance imaging (bpMRI) for the detection of clinically significant prostate cancer (csPCa) in biopsy-naïve patients. Method This retrospective study included 324 patients who underwent bpMRI and MRI targeted fusion biopsy (MRGB) and/or systematic biopsy, of them 217 were randomly assigned to the training group and 107 were assigned to the validation group. We assessed the diagnostic performance of three bpMRI-based scorings in terms of sensitivity and specificity. Subsequently, 3 models (Model 1, Model 2, and Model 3) combining bpMRI scorings with clinical variables were constructed and compared with each other using the area under the receiver operating characteristic (ROC) curves (AUC). The statistical significance of differences among these models was evaluated using DeLong’s test. Results In the training group, 68 of 217 patients had pathologically proven csPCa. The sensitivity and specificity for Scoring 1 were 64.7% (95% CI 52.2%-75.9%) and 80.5% (95% CI 73.3%-86.6%); for Scoring 2 were 86.8% (95% CI 76.4%-93.8%) and 73.2% (95% CI 65.3%-80.1%); and for Scoring 3 were 61.8% (95% CI 49.2%-73.3%) and 80.5% (95% CI 73.3%-86.6%), respectively. Multivariable regression analysis revealed that scorings based on bpMRI, age, and prostate-specific antigen density (PSAD) were independent predictors of csPCa. The AUCs for the 3 models were 0.88 (95% CI 0.83–0.93), 0.90 (95% CI 0.85–0.94), and 0.88 (95% CI 0.83–0.93), respectively. Model 2 showed significantly higher performance than Model 1 (P = 0.03) and Model 3 (P

Aiming at the characteristics that the signal noise ratio (SNR) gradually decreases from the near to far range of the swath, an adaptive phase filtering algorithm based on Goldstein filtering and combined with multiple quality-guided graphs was proposed. Firstly, the components used to determine the filtering parameters were obtained through residue density, pseudo-coherence coefficient and pseudo-SNR, the three quality-guided graphs. Then, the filter parameters were calculated by weighting the three components. Finally, the size of filtering window was determined according to the account of residues, and the interferometric phase noise was removed in frequency domain. Simulated data, TSX/TDX data and airborne interferometric imaging radar altimeter data were used to verify the performance of the new algorithm. Compared with the results of Goldstein filtering and its improved algorithms, the results showed that the proposed algorithm can effectively filter out phase noise while maintaining the edge characteristics of interferometric fringe. The section of filtering result can well match with the section of simulated pure interfeometric phase. Moreover, the algorithm proposed in this paper can effectively remove the noise in the interferogram of TSX/TDX sea ice data, and the residues' filtering rate was above 86%, which can effectively remove the phase residues of the sea ice surface while maintaining the characteristics of the sea ice edge. Experimental results showed that the new algorithm provides an effective phase noise filtering method for imaging radar altimeter data processing.

The core structure and Peierls stress of 30° partial dislocation are researched on the basis of lattice theory of dislocation to further recognize the mechanical properties of CdTe. The surface effect and elastic strain energy missed in classical PN model have been considered in calculations. In addition, the influences of γ- surface fitting on estimation of core width and Peierls stress are analysed. Research results indicate that the rectification of surface effect to dislocation fundamental properties is more evident for narrower dislocations. Since the intrinsic stacking-fault energy(SFE) of CdTe is far lower than the unstable SFE, the difference between the results calculated by using original and effective γ- surface is negligible. More extensive, for crystal whose SFE satisfies the condition mentioned, the original γ- surface can be used for investigation of dislocation properties directly. The deviation of fitted γ- surface from the numerical result will result in non-negligible influence on the estimated result of Peierls stress, and affect the analysis of metastable state. The core width and Peierls stress are about 0.64∼0.73b and 1∼2GPa, respectively. The research results are useful for better understanding and utilization of semiconductor CdTe.

The influences of hydrogen peroxide (H2O2) on the storability and metabolism of disease-resistant substances in fresh longan were investigated. Compared to the control samples, H2O2-treated longan exhibited a higher index of fruit disease, pericarp browning, and pulp breakdown, a higher rate of fruit weight loss, but lower chromaticity values (L*, a* and b*) in pericarp appearance, and a lower commercially acceptable fruit rate. Additionally, H2O2-treated longan showed a lower lignin content, lower activities of enzymes including phenylalnine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), 4-coumaryl coenzyme A ligase (4-CL), cinnamate dehydrogenase (CAD), peroxidase (POD), chitinase (CHI), and β-1,3-glucanase (GLU). These data collectively suggest that H2O2 negatively impacted the storability of fresh longan. This can be attributed to H2O2′s role in reducing the levels of disease-resistant substances and suppressing the activities of disease-resistant enzymes, implying that H2O2 reduced the postharvest storability of longan by compromising its disease resistance.

Abstract This meta-analysis was conducted to summarize the effects of n-3 polyunsaturated fatty acid (n-3 PUFA) on metabolic status including insulin metabolism and lipid metabolism in women with polycystic ovary syndrome (PCOS) by randomized controlled trials (RCTs). Four mainstream databases including PubMed, Cochrane Library, Embase and Web of Science were searched from their inception to October 2021. The registration number of this study was CRD42021285233. The quality assessment was performed referring the Cochrane Risk of Bias Tool. Mean differences (MD) and 95% confidence intervals (CIs) were generated for continuous variables by meta-analysis. Subgroup analyses were performed based on study duration (≤ 8 weeks or > 8 weeks), the source of n-3 PUFA (marine derived or plant origins) and dosage of n-3 PUFA (≤ 1000 mg/d or > 1000 mg/d). Eventually, 11 RCTs reporting 816 patients were enrolled. Compared with control group, n-3 PUFA treatment decreased waist circumference (MD = -2.76, 95% CI: -3.82 to -1.69; p 8 weeks regardless of the source and the dosage to retard the pathogenesis of PCOS related metabolic diseases.

Introduction: Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered. Objectives: To characterize the alterations of oral and gut microbiota and their roles in HTN. Methods: We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN. Results: BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition. Conclusions: PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.

Abstract Non-Hermiticity has widespread applications in quantum physics. It brings about distinct topological phases without Hermitian counterparts, and gives rise to the fundamental challenge of phase classification. Here, we report an experimental demonstration of unsupervised learning of non-Hermitian topological phases with the nitrogen-vacancy center platform. In particular, we implement the non-Hermitian twister model, which hosts peculiar knotted topological phases, with a solid-state quantum simulator consisting of an electron spin and a nearby 13C nuclear spin in a nitrogen-vacancy center in diamond. By tuning the microwave pulses, we efficiently generate a set of experimental data without phase labels. Furthermore, based on the diffusion map method, we cluster this set of experimental raw data into three different knotted phases in an unsupervised fashion without a priori knowledge of the system, which is in sharp contrast to the previously implemented supervised learning phases of matter. Our results showcase the intriguing potential for autonomous classification of exotic unknown topological phases with experimental raw data.

The discreteness correction for simple lattices has been determined, however, there is still no detailed and rigorous derivation of the discreteness correction for compound lattices due to the relatively complex structure (simple lattices have only one set per slip system, while complex lattices have at least two sets). A lattice dynamics model which takes into account the energy increments caused by changes in bond length and bond angle is constructed for sphalerite crystals and the relationships between discreteness parameters and elastic constants are determined for the $\left\langle 110\right\rangle \left\{111\right\}$ slip system. Compared to glide set, the discreteness correction for shuffle set is much larger due to it is mainly contributed by the interactions between nearest neighbor atoms. Based on the results obtained from the model, the dislocations in ZnS crystal are investigated. The theoretical prediction result of Peierls stress for shuffle $60{\rm{^\circ }}$ dislocation closely matches the experimental critical shear stress. It is inferred that the initial plastic deformation of ZnS is closely related to the movement of shuffle $60{\rm{^\circ }}$ dislocations.

β-Farnesene is an advanced molecule with promising applications in agriculture, the cosmetics industry, pharmaceuticals, and bioenergy. To supplement the shortcomings of rational design in the development of high-producing β-farnesene strains, a Metabolic Pathway Design-Fermentation Test-Metabolomic Analysis-Target Mining experimental cycle was designed. In this study, by over-adding 20 different amino acids/nucleobases to induce fluctuations in the production of β-farnesene, the changes in intracellular metabolites in the β-farnesene titer-increased group were analyzed using non-targeted metabolomics. Differential metabolites that were detected in each experimental group were selected, and their metabolic pathways were located. Based on these differential metabolites, targeted strain gene editing and culture medium optimization were performed. The overexpression of the coenzyme A synthesis-related gene pantothenate kinase (PanK) and the addition of four mixed water-soluble vitamins in the culture medium increased the β-farnesene titer in the shake flask to 1054.8 mg/L, a 48.5% increase from the initial strain. In the subsequent fed-batch fermentation, the β-farnesene titer further reached 24.6 g/L. This work demonstrates the tremendous application value of metabolomics analysis for the development of industrial recombinant strains and the optimization of fermentation conditions.

Adenomyosis is a common gynecological disease in reproductive women, which causes serious dysmenorrhea, menorrhagia, anemia, and infertility, and has a serious impact on the physical and mental health of women. Considering that the efficacy of the traditional medication and surgical treatment is not ideal, an increasing number of patients are searching for more effective and less invasive therapies. Ultrasound (US)-guided microwave ablation (MWA) has emerged as a new effective and minimally invasive alternative treatment for symptomatic adenomyosis, and it is widely being used in clinical settings. Several studies have proven that it is an efficient and safe treatment modality for symptomatic adenomyosis, but a significant variance in clinical outcomes reported in previous studies was also observed. Herein, we have analyzed the potential causes of this problem from the aspects of the diagnosis of adenomyosis, symptom evaluation before ablation, steps of US-guided ablation treatment, and outcome evaluation after ablation. Simultaneously, the clinical problems existing in the ablation treatment of adenomyosis are discussed, and the directions of future research are pointed out.

Machine learning has been applied to problems in condensed matter physics, but its performance in an experimental setting needs testing. Zhang et al. study the effects of adversarial perturbations on a neural-network-based topological phase classifier, applied to experimental data from an NV center in diamond.

Steam flooding is an effective development method for heavy oil reservoirs, and the steam flooding assisted by the profile control system can plug the dominant channels and further improve the recovery factor. High-temperature-resistant foam as a profile control system is a hot research topic, and the key lies in the optimal design of the foam system. In this paper, lignin was modified by sulfonation to obtain a high-temperature-resistant modified lignin named CRF; the foaming agent CX-5 was confirmed to have good high-temperature foaming ability by reducing the surface tension; the formula of the profile control system (A compound system of CRF and CX-5, abbreviated as PCS) and the best application parameters were optimized by the foam resistance factor. Finally, the effect of PCS-assisted steam flooding in enhanced oil recovery was evaluated by single sand packing tube flooding, three parallel tube flooding, and large-scale sand packing model flooding experiments. The results show that CX-5 has a good high-temperature foaming performance; the foam volume can reach more than 180 mL at 300 °C, and the half-life is more than 300 s. The optimal PCS formulation is 0.3 wt% CRF as an oil displacement agent + 0.5 wt% CX-5 as a foaming agent. The optimal gas–liquid ratio range is 1:2 to 2:1, and the high pressure and permeability are more conducive to the generation and stability of the foam. Compared with steam flooding, PCS-assisted steam flooding can improve oil recovery by 9% and 7.9% at 200 °C and 270 °C, respectively. PCS can effectively improve the heterogeneity of the reservoir, and increase the oil recovery of the three-parallel tube flooding experiment by 28.7%. Finally, the displacement results of the sand-packing model with large dimensions show that PCS can also expand the swept volume of the homogeneous model, but the effect is 9.46% worse than that of the heterogeneous model.

Background: Lipid profiles differ naturally between individuals and between populations. So far, the data relating to non-fasting lipid profiles has been derived predominantly from studies on Western population. The characteristics and clinical significance of non-fasting lipids in Chinese patients with coronary heart disease (CHD) in response to traditional Chinese diets remain poorly understood. Methods: A total of 1022 Chinese CHD patients with coronary artery luminal stenosis >40% as diagnosed by coronary artery angiography were enrolled in the study. All patients received standard treatment for CHD, including statins. They were divided into an intermediate stenosis group (luminal stenosis 40–70%, n = 486) or a severe stenosis group (luminal stenosis >70%, n = 536). Their blood lipid profiles were measured in the fasting state, and 4 hours after normal breakfast. All participants were followed up for five years. Major adverse cardiovascular events (MACE) including all-cause death, cardiac death, myocardial infarction, unscheduled coronary revascularization and stroke were recorded. Results: After normal breakfast intake, patients with intermediate or severe stenosis showed an apparent increase in the levels of triglyceride (TG), remnant cholesterol (RC) and Apo (apolipoprotein) A1 compared to the fasting state, but a significant reduction in the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), Apo B and Apo E. In addition to the traditional risk factors (older age, male, diabetes and smoking) and coronary artery stenosis, the fasting levels of LDL-C and Apo B, as well as non-fasting levels of HDL-C and Apo A1, were identified as independent predictors of 5-year MACE occurrence by multivariate Cox proportional hazards analysis. Patients in the 1st tertile of the non-fasting HDL-C group (1.07 mmol/L) (1st tertile: 2.786, 95% CI (confidence intervals) [1.808, 4.293], p < 0.001). Conclusions: This prospective observational study found that lipid profiles in either the fasting or non-fasting states were associated with the long-term risk of MACE in Chinese CHD patients. In addition to the fasting LDL-C level, a low non-fasting HDL-C level may also be an independent risk factors for cardiovascular events. Measurement of lipid profiles during the non-fasting state may be feasible for the management of CHD patients in routine clinical practice in China.

Low glume coverage is the preferred for easy threshing in grain production, but the genetic basis remains unclear. Here, the authors report the gene GC1, which encodes an atypical G protein γ subunit, negatively regulates sorghum glume coverage and the naturally truncated alleles can be useful in the naked grain breeding.

In this study, a two-compartment biofilm reactor was designed for iturin A production. The biofilm reactor consists of a stirred-tank fermentor containing exclusively suspended cells and a packing column where the biofilm is attached. Polyester fiber with sphere shape and rough surfaces was chosen as the carrier of biofilm in packing column. Batch, fed-batch, and repeated-batch fermentation using Bacillus velezensis ND in the biofilm reactor were studied. Compared to conventional suspended cell fermentations, the productivity of iturin A in batch and fed-batch biofilm fermentation were increased by 66.7% and 63.3%, respectively. Maximum itutin A concentration of 6.8 ± 0.1 g/L and productivity of 46.9 ± 0.2 mg/L/h were obtained in fed-batch biofilm fermentation. Repeated-batch fermentation showed high stability, with almost same profile as batch fermentation. After a step-wise temperature control strategy was introduced in the biofilm reactor, productivity of iturin A was increased by 131.9% compared to suspended cell reactor. This superior performance of biofilm reactor confirms that it has great potential in industrial production of iturin A.

For thousands of years, caries, periodontitis and mucosal diseases, which are closely related to oral microorganisms, have always affected human health and quality of life. These complex microbiota present in different parts of the mouth can cause chronic infections in the oral cavity under certain conditions, some of which can also lead to acute and systemic diseases. With the mutation of related microorganisms and the continuous emergence of drug-resistant strains, in order to prevent and treat related diseases, in addition to the innovation of diagnosis and treatment technology, the development of new antimicrobial drugs is also important. Catechins are polyphenolic compounds in green tea, some of which are reported to provide health benefits for a variety of diseases. Studies have shown that epigallocatechin-3-gallate (EGCG) is the most abundant and effective active ingredient in green tea catechins, which acts against a variety of gram-positive and negative bacteria, as well as some fungi and viruses. This review aims to summarize the research progress on the activity of EGCG against common oral disease-associated organisms and discuss the mechanisms of these actions, hoping to provide new medication strategies for the prevention and treatment of oral infectious diseases, the future research of EGCG and its translation into clinical practice are also discussed.

Abstract Background Dystrophinopathy, a common neuromuscular disorder, includes Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Many researches are currently ongoing to develop curative approaches, which results in an urgent need for biomarkers of disease progression and treatment response. This study investigated whether the serum creatinine (SCRN) level can be used as a biomarker of disease progression in dystrophinopathy. Methods We enrolled 377 male patients with dystrophinopathy and 520 male non-dystrophinopathy controls in a cross-sectional study. From this cohort, 113 follow-up patients were enrolled in a longitudinal study. Patients’ demographic information, motor function, muscle fatty infiltration, and muscle dystrophin levels were evaluated. We investigated correlations between these parameters and SCRN levels, and determined changes in SCRN levels with maturation and with motor function changes. Results Our results showed SCRN levels correlated with motor function (FDR

BackgroundCholesterol crystals (CCs) in lesions are the hallmark of advanced atherosclerotic plaque. Previous studies have demonstrated that CCs could activate NLRP3 inflammasome, which played an important role in atherosclerotic lesion progression. However, the relationship between CCs, NLRP3 inflammasome pathway, and plaque vulnerability in patients with ACS is still not elucidated.MethodsTwo hundred sixty-nine consecutive acute coronary syndrome (ACS) patients with 269 culprit lesions were included in this study. CCs and other plaque characteristics within the culprit lesion segment were evaluated by optical coherence tomography (OCT) before percutaneous coronary intervention (PCI). The NLRP3 mRNA expression in peripheral blood mononuclear cells (PBMCs) and the serum levels of interleukin (IL)-1β, IL-18, and other biological indices were measured.ResultsCholesterol crystals were observed in 105 (39%) patients with 105 culprit lesions. There were no significant differences in baseline clinical characteristics between the patients with CCs (CCs group, n = 105) and the patients without CCs (non-CCs group, n = 164) within the culprit lesion segment except for lipoprotein(a) [Lp(a)]. The CCs group had a higher level of NLRP3 mRNA expression in PBMCs and higher levels of serum cytokine IL-1β and IL-18. OCT showed that the CCs group had longer lesion length, more severe diameter stenosis, and less minimum luminal area (MLA) than the non-CCs group (all p < 0.05). The frequency of thin-cap fibroatheroma (TCFA), thrombus, accumulation of macrophages, plaque rupture, micro-channel, calcification, spotty calcification, and layered plaque was higher in the CCs group than in the non-CCs groups (all p < 0.05). Multivariate logistic analysis revealed that the level of NLRP3 expression (OR = 10.204), IL-1β levels (OR = 3.523), IL-18 levels (OR = 1.006), TCFA (OR = 3.593), layered plaque (OR = 5.287), MLA (OR = 1.475), macrophage accumulation (OR = 2.881), and micro-channel (OR = 3.185) were independently associated with CCs.ConclusionAcute coronary syndrome patients with CCs in culprit lesions had a higher expression of NLRP3, IL-1β, and IL-18, and had more vulnerable plaque characteristics than patients without CCs. CCs might have interacted with NLRP3 inflammasome activation in patients with ACS, which could contribute to plaque vulnerability in culprit lesions.

Gene therapy has revolutionized the field of medicine, offering new hope for those with common and rare diseases. For nearly three decades, adeno-associated virus (AAV) has shown significant therapeutic benefits in multiple clinical trials, mainly due to its unique replication defects and non-pathogenicity in humans. In the field of cardiovascular disease (CVD), compared with non-viral vectors, lentiviruses, poxviruses, and adenovirus vectors, AAV possesses several advantages, including high security, low immunogenicity, sustainable and stable exogenous gene expression etc., which makes AAV one of the most promising candidates for the treatment of many genetic disorders and hereditary diseases. In this review, we evaluate the current information on the immune responses, transport pathways, and mechanisms of action associated with AAV-based CVD gene therapies and further explore potential optimization strategies to improve the efficiency of AAV transduction for the improved safety and efficiency of CVD treatment. In conclusion, AAV-mediated gene therapy has great potential for development in the cardiovascular system.

Background: Assessment of renal lesions and deficiency accurately remains critical in the diagnosis of congenital anomalies of the kidneys and urinary tracts (CAKUT) in children. Advanced imaging such as Magnetic resonance Imaging (MRI) and Diffusion weighted Imaging (DWI) allows structural and functional insufficiency to be detected. Currently, radiomics machine learning models are being explored as full-automated diagnostic tools. We aimed to develop a machine learning integrated radiomics model to predict renal anomalies and deficiency in children.Methods: A retrospective study of 280 children with MRI/DWI were enrolled between 2018 and 202 at a children’s hospital. A total of 1,037 radiomics features were extracted from the DWI images of each participant, which were divided into training set and test set (8:2 split). Using 5-fold cross-validated method, multiple machine learning algorithms were employed to predict renal lesions and deficiency when compared with the radiologist’s diagnosis based on DWI, 99mTc-labeled dimercaptosuccinic acid (DMSA) SPECT cortical renal scintigraphy or 99mTc-labeled diethylenetriamine pentaacetate (DTPA) renal scan.Results: For detecting the kidney lesions, the LASSO + Random Forest algorithm outperformed other classifiers with an accuracy of 0.750 (95% confidence interval, 0.734–0.766) and area under the curve (AUC) of 0.765 (95% confidence interval, 0.700–0.831). The performance of classifiers did not show a significant difference (p > 0.05) in detecting bilateral or unilateral kidney lesions by DWI scanning. The classifiers performed significantly better in bilateral kidney deficit than in unilateral kidney deficit (p < 0.05). We next built prediction models for renal deficiency using the radiomics signature and clinical features compared to renal scintigraphy. The ensemble model had a high-test accuracy of 80.9% ± 4.2% and a sensitivity of 91.7% ± 7.1% with a moderate calibration.Conclusion: An ensemble model integrated with DWI-radiomic and clinical features can be utilized to predict renal lesions and deficiency in children with CAKUT.

Background Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of patients with heart failure. Clinically, HFpEF prevalence shows age and gender biases. Although the majority of patients with HFpEF are elderly, there is an emergence of young patients with HFpEF. A better understanding of the underlying pathogenic mechanism is urgently needed. Here, we aimed to determine the role of aging in the pathogenesis of HFpEF. Methods and Results HFpEF dietary regimen (high‐fat diet + Nω‐Nitro‐L‐arginine methyl ester hydrochloride) was used to induce HFpEF in wild type and telomerase RNA knockout mice (second‐generation and third‐generation telomerase RNA component knockout), an aging murine model. First, both male and female animals develop HFpEF equally. Second, cardiac wall thickening preceded diastolic dysfunction in all HFpEF animals. Third, accelerated HFpEF onset was observed in second‐generation telomerase RNA component knockout (at 6 weeks) and third‐generation telomerase RNA component knockout (at 4 weeks) compared with wild type (8 weeks). Fourth, we demonstrate that mitochondrial respiration transitioned from compensatory state (normal basal yet loss of maximal respiratory capacity) to dysfunction (loss of both basal and maximal respiratory capacity) in a p53 dosage dependent manner. Last, using myocardial‐specific p53 knockout animals, we demonstrate that loss of p53 activation delays the development of HFpEF. Conclusions Here we demonstrate that p53 activation plays a role in the pathogenesis of HFpEF. We show that short telomere animals exhibit a basal level of p53 activation, mitochondria upregulate mtDNA encoded genes as a mean to compensate for blocked mitochondrial biogenesis, and loss of myocardial p53 delays HFpEF onset in high fat diet + Nω‐Nitro‐L‐arginine methyl ester hydrochloride challenged murine model.

Abstract Background Mutations in the DMD gene encoding dystrophin—a critical structural element in muscle cells—cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. Methods In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46–54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. Results Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan. Conclusions We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.

Mobile videos contain a large amount of data, where the information interesting to the user can either be discrete or distributed. This paper introduces a method for fusing 3D geographic information systems (GIS) and video image textures. For the dynamic fusion of video in 3DGIS where the position and pose angle of the filming device change moment by moment, it integrates GIS 3D visualization, pose resolution and motion interpolation, and proposes a projection texture mapping method for constructing a dynamic depth camera to achieve dynamic fusion. In this paper, the accuracy and time efficiency of different systems of gradient descent and complementary filtering algorithms are analyzed mainly by quantitative analysis method, and the effect of dynamic fusion is analyzed by the playback delay and rendering frame rate of video on 3DGIS as indicators. The experimental results show that the gradient descent method under the Aerial Attitude Reference System (AHRS) is more suitable for the solution of smartphone attitude, and can control the root mean square error of attitude solution within 2°; the delay of video playback on 3DGIS is within 29 ms, and the rendering frame rate is 34.9 fps, which meets the requirements of the minimum resolution of human eyes.

ObjectivesPlaque vulnerability and rupture rather than plaque size are the major cause of clinical events in patients with intermediate coronary lesions. Therefore, the present study was aimed to explore potential markers associated with plaque rupture in acute coronary syndrome (ACS) patients with intermediate coronary lesions.MethodsA total of 82 ACS patients presenting with only intermediate coronary lesions (40–70% stenosis demonstrated by quantitative coronary angiography) and no severe stenosis in other main coronary arteries [median age 63 years, 53 male and 29 female] were enrolled. Plaque morphology were assessed by optical coherence tomography (OCT). Hematological indices were assayed by automated hematological analyzer.ResultsPlaque rupture was identified in 14 patients by OCT. Neutrophil to lymphocyte ratio (NLR) in patients with plaque rupture (n = 14) was significantly higher than that in patients with non-plaque rupture (n = 68) [3.85 (3.28, 4.77) vs. 2.13 (1.40, 2.81), p < 0.001]. Multivariate logistic regression analysis revealed that NLR was one of the independent risk factors for plaque rupture in intermediate coronary artery lesions (odds ratio 1.64, 95% confidence intervals 1.18–2.29, p = 0.003). ROC curve analysis found a cutoff point of NLR > 2.94 for plaque rupture with 93.8% sensitivity and 77.9% specificity.ConclusionNLR, an inflammatory biomarker, is closely associated with plaque rupture in intermediate coronary artery lesions. Monitoring NLR may be useful in risk stratification and management for intermediate coronary artery lesions.

Objective: We aimed to find crucial microRNAs (miRNAs) associated with the development of atrial fibrillation (AF), and then try to elucidate the possible molecular mechanisms of miRNAs in AF. Methods: The miRNA microarray, GSE68475, which included 10 right atrial appendage samples from patients with persistent AF and 11 samples from patients with normal sinus rhythm, was used for the analysis. After data preprocessing, differentially expressed miRNAs were screened using limma. Target genes of miRNAs were predicted using miRWalk2.0. We then conducted functional enrichment analyses for miRNA and target genes. Protein-protein interaction (PPI) network and module analyses for target genes were performed. Finally, transcription factors (TFs)-target genes regulatory network was predicted and constructed. Results: Seven genes, including CAMK2D, IGF2R, PPP2R2A, PAX6, POU3F2, YWHAE, and AP2A2, were targeted by TFs. Among these seven genes, CAMK2D (targeted by miR-31-5p), IGF2R (targeted by miR-204-5p), PAX6 (targeted by miR-223-3p), POU3F2 (targeted by miR-204-5p), YWHAE (targeted by miR-31-5p), and AP2A2 (targeted by miR-204-5p) belonged to the top 10 degree genes in the PPI network. Notably, MiR-204-5p, miR-31-5p, and miR-223-3p had more target genes. Besides, CAMK2D was enriched in some pathways, such as adrenergic signaling in cardiomyocytes pathway and cAMP signaling pathway. YWHAE was enriched in the Hippo signaling pathway. Conclusion: miR-31-5p played a crucial role in cardiomyocytes by targeting CAMK2D and YWHAE via cAMP and Hippo signaling pathways. miR-204 was involved in the progression of AF by regulating its target genes IGF2R, POU3F2, and AP2A2. On the other hand, miR-223-3p functioned in AF by targeting PAX6, which was associated with the regulation of apoptosis in AF. This study would provide a theoretical basis and potential therapeutic targets for the treatment of AF. (Anatol J Cardiol 2020; 23: 324-33)

Compared with low-yield extraction from plants and environmentally unfriendly chemical synthesis, biocatalysis by asparagine synthetase (AS) for preparation of L-asparagine (L-Asn) has become a potential synthetic method. However, low enzyme activity of AS and high cost of ATP in this reaction restricts the large-scale preparation of L-Asn by biocatalysis. In this study, gene mining strategy was used to search for novel AS with high enzyme activity by expressing them in Escherichia coli BL21 (DE3) or Bacillus subtilis WB600. The obtained LsaAS-A was determined for its enzymatic properties and used for subsequent preparation of L-Asn. In order to reduce the use of ATP, a class III polyphosphate kinase 2 from Deinococcus ficus (DfiPPK2-Ⅲ) was cloned and expressed in E. coli BL21 (DE3), Rosetta (DE3) or RosettagamiB (DE3) for ATP regeneration. A coupling reaction system including whole cells expressing LsaAS-A and DfiPPK2-Ⅲ was constructed to prepare L-Asn from L-aspartic acid (L-Asp). Batch catalytic experiments showed that sodium hexametaphosphate (>60 mmol L−1) and L-Asp (>100 mmol L−1) could inhibit the synthesis of L-Asn. Under fed-batch mode, L-Asn yield reached 90.15% with twice feeding of sodium hexametaphosphate. A final concentration of 218.26 mmol L−1 L-Asn with a yield of 64.19% was obtained when L-Asp and sodium hexametaphosphate were fed simultaneously.

This study is oriented towards machine autonomous mapping and the need to improve the efficiency of map point symbol recognition and configuration. Therefore, an intelligent recognition method for point symbols was developed using the You Only Look Once Version 3 (YOLOv3) algorithm along with the Convolutional Block Attention Module (CBAM). Then, the recognition results of point symbols were associated with the point of interest (POI) to achieve automatic configuration. To quantitatively analyze the recognition effectiveness of this study algorithm and the comparison algorithm for map point symbols, the recall, precision and mean average precision (mAP) were employed as evaluation metrics. The experimental results indicate that the recognition efficiency of point symbols is enhanced compared to the original YOLOv3 algorithm, and that the mAP is increased by 0.55%. Compared to the Single Shot MultiBox Detector (SSD) algorithm and Faster Region-based Convolutional Neural Network (Faster RCNN) algorithm, the precision, recall rate, and mAP all performed well, achieving 97.06%, 99.72% and 99.50%, respectively. On this basis, the recognized point symbols are associated with POI, and the coordinate of point symbols are assigned through keyword matching and enrich their attribute information. This enables automatic configuration of point symbols and achieves a relatively good effect of map configuration.

The community is the basic spatial unit for urban residents to live and rest. It is a crucial direction of city image research to explore people’s cognitive characteristics of community space image. Aiming at the lack of cognitive quantification of community spatial images, a new method that can quantify community spatial data into cognitive results is proposed. By employing spatial analysis tools, eleven spatial indicators from the perspective of community spatial form and spatial services are selected, and an image structure is constructed based on the characteristics of the indicator results. The results of multiple indicators are organized through the improved technique for order preference by similarity to ideal solution (TOPSIS) and overlay analysis method to produce a spatial image map of the community. The study displays that the spatial image characteristics of the community scale can be comprehensively expressed through three types of elements: district, path (edge), and node (landmark). These three types of elements constitute the image structure at the community scale and present apparent elements’ characteristics. This scrutiny is also aimed to demonstrate the construction and use process of the methodology and to provide new ideas for the cognitive research of urban spatial image at the community scale.

The problem of corruption in socio-economic development has long been a focus of academics and practitioners. To address this concern in China, the 18th National Congress of the Communist Party of China instituted a new anti-corruption policy. In this paper, we examine the impact of this recently enacted anti-corruption policy on the investment efficiency of subsidized enterprises from the perspective of government subsidies. We conclude that government subsidies have a significant positive impact on the overinvestment behavior of enterprises and that the anti-corruption work done by the government has effectively restrained the excessive investment behavior of government-subsidized enterprises. Further, we find that the anti-corruption policy is more effective in restricting overinvestment in subsidized state-owned enterprises than in non-state-owned enterprises. We examine the impact of the anti-corruption policy on excessive investment caused by government subsidies and enrich the body of research related to investment efficiency. We also provide empirical support for further research on the anti-corruption policy at the macro-market and micro-enterprise levels. The findings highlight the need to establish new cooperation between government and enterprises, to rationalize the distribution of administrative resources, and to promote the sustained and healthy development of the national economy. Keywords: Anti-corruption, Government subsidies, Investment efficiency, Type of controlling shareholders

Objective: Dysferlin deficiency causes dysferlinopathy. This study aimed to expand the mutational spectrum of dysferlinopathies, to further study one case with diagnostic ambiguity, and to identify the diagnostic value of dysferlin expression in total peripheral blood mononuclear cells (PBMC).Methods: The clinical and molecular profiles of dysferlinopathies in eight Chinese patients were evaluated. We also conducted magnetic resonance imaging (6/8) and determined dysferlin protein expression in muscle (7/8) and PBMC (3/8).Results: Nine of the 13 DYSF mutations identified were novel. One patient was homozygous for the Gln111Ter mutation by genomic DNA sequencing but was found to be heterozygous by sequencing of cDNA from total PBMC. A daughter of this patient did not carry any Gln111Ter mutation. Abnormal muscle MRI with predominant involvement of the medial gastrocnemius and soleus muscle was observed in 5/6 patients. Dysferlin levels were significantly reduced (immunohistochemistry/immunoblot) or absent (immunohistochemistry) in muscle and total PBMC (26–39%) for most patients. Sarcoplasmic accumulation of dysferlin was detected in one patient.Conclusion: Genomic DNA sequencing detects frequent homozygous mutations, while fewer heterozygous mutations in cDNA are detected after posttranscription. Total PBMC may serve as an alternative to confirm diagnosis and to guide further testing in dysferlinopathies. Our results contribute to the mutational spectrum of dysferlinopathies.

BackgroundWith the widespread use of broad-spectrum antibiotics, the problem of bacterial resistance has become a global crisis. To monitor bacterial resistance in our hospital, the distribution of specimens, the detection of pathogens and their drug resistance from July 2005 to June 2007 (13 years ago) and July 2018 to June 2020 were compared and analyzed.MethodsOrdinary specimens (such as sputum, urine, feces, and secretion) were inoculated in blood AGAR media, MacConkey medium, chocolate medium, double SS medium and selective culture medium. Blood, cerebrospinal fluid, pleural effusion, joint cavity effusion and other sterile body fluid samples were inoculated in aerobic and anaerobic blood culture flasks. Automatic microbial identification, drug sensitivity analysis and mass spectrometry analysis were used to determine their drug sensitivity.ResultsCompared with the results obtained 13 years ago, the number of specimens submitted for inspection in the past two years has increased significantly, exhibiting a growth rate of 283%. The changes in the pathogen species were obvious. Gram-positive cocci were the dominant bacteria 13 years ago, and Gram-negative bacilli were the dominant bacteria in the past two years. In addition, the resistance of several major Gram-negative bacilli to piperacillin/tazobactam, cefoperazone/sulbactam, meropenem and imipenem all showed an increasing trend.ConclusionThe variety of pathogenic bacteria in our hospital has changed significantly in the past two years compared with that 13 years ago, and the clinical isolates of Gram-negative bacilli have increased significantly compared with Gram-positive cocci. In the clinical treatment of anti-infective diseases, antimicrobial agents should be selected according to the bacterial distribution characteristics and drug resistance in each hospital.

The second-order elastic constants, third-order elastic constants, and the generalized-stacking-fault energy for semiconductor GaAs are investigated using the first-principles calculations. The predictions of elastic constants are obtained from the coefficients of the fitted polynomials of the energy-strain functions. It is found that the nonlinear elastic effects must be considered when the applied deformations are larger than approximately 1.5%. With the Lagrangian strains up to 6.4%, the terms included up to third order in energy expansion functions are sufficient. The elastic constants given in this work agree well with the previous results and experimental data except for C144. C144 given by the present paper is a positive value, and the estimated 3 GPa agrees well with the experimental result of 2 GPa. The research results can provide a reference for understanding the elasticity of GaAs. The generalized-stacking-fault energy has been calculated without and with structural relaxation, respectively. The unstable stacking fault energy with structural relaxation is about two-thirds of that without relaxation. The dislocation width and Peierls stress for 30° partial in GaAs have been investigated based on the improved P-N theory. The dislocation width is very narrow (only about one-fifth of Burgers vector b), which is reasonable for covalent materials. The Peierls stress is about 4 GPa, in good agreement with the experimental result of 2∼3 GPa.

Background: Duchenne muscular dystrophy (DMD) is a fatal, X-linked recessive muscle disorder characterized by heterogeneous progression and severity. We aimed to study the effects of single nucleotide polymorphisms (SNPs) in SPP1 and LTBP4 on DMD progression in Chinese patients.Methods: We genotyped LTBP4 haplotypes and the SPP1 promoter SNPs rs28357094, rs11730582, and rs17524488 in 326 patients registered in the neuromuscular database of The First Affiliated Hospital of Sun Yat-sen University. Kaplan-Meier curves and log-rank tests were used to estimate and compare median age at loss of ambulation, while Cox proportional hazard regression models were used as to analyze the effects of glucocorticoids treatments, DMD genotype, and SPP1/LTBP4 SNPs on loss of ambulation.Results: The CC/CT genotype at rs11730582 was associated with a 1.33-year delay in ambulation loss (p = 0.006), with hazard ratio 0.63 (p = 0.008), in patients with truncated DMD genotype and undergoing steroid treatment. On the other hand, rs17524488 in SPP1 and the IAAM/IAAM haplotype in LTBP4 were not associated with time to ambulation loss.Conclusions:SPP1 rs11730582 is a genetic modifier of the long-term effects of steroid treatment in Chinese DMD patients. Thus, any future clinical study in DMD should adjust for glucocorticoids use, DMD genotype, and SPP1 polymorphisms.

Among many genes encoding for amino acid dehydrogenase, a novel leucine dehydrogenase gene from Exiguobacterium sibiricum (EsiLeuDH) was isolated by using genome mining strategy. EsiLeuDH was overexpressed in Escherichia coli BL21 (DE3), followed by purification and characterization. The high thermostability of the enzyme confers its half-life up to 14.7 h at 50°C. Furthermore, the substrate specificity shows a broad spectrum, including many L-amino acids and aliphatic α-keto acids, especially some aryl α-keto acids. This enzyme coupled with recombinant formate dehydrogenase (FDH) was used to catalyze trimethylpyruvic acid (TMP) through reductive amination to generate enantiopure L-tert-leucine (L-Tle). In order to overcome the substrate inhibition effect, a fed-batch feeding strategy was adopted to transform up to 0.8 M of TMP to L-Tle, with an average conversion rate of 81% and L-Tle concentration of 65.6 g⋅L–1. This study provides a highly efficient biocatalyst for the synthesis of L-Tle and lays the foundation for large-scale production and application of chiral non-natural amino acids.

The elastic constants, core width and Peierls stress of 30° partial dislocation in germanium has been investigated based on the first-principles calculations and the improved Peierls–Nabarro model. Our results suggest that the predictions of lattice constant and elastic constants given by LDA are in better agreement with experiment results. While the lattice constant is overestimated at about 2.4% and most elastic constants are underestimated at about 20% by the GGA method. Furthermore, when the applied deformation is larger than 2%, the nonlinear elastic effects should be considered. And with the Lagrangian strains up to 8%, taking into account the third-order terms in the energy expansion is sufficient. Except the original γ—surface generally used before (given by the first-principles calculations directly), the effective γ—surface proposed by Kamimura et al. derived from the original one is also used to study the Peierls stress. The research results show that when the intrinsic−stacking−fault energy (ISFE) is very low relative to the unstable−stacking−fault energy (USFE), the difference between the original γ—surface and the effective γ—surface is inapparent and there is nearly no difference between the results of Peierls stresses calculated from these two kinds of γ—surfaces. As a result, the original γ—surface can be directly used to study the core width and Peierls stress when the ratio of ISFE to the USFE is small. Since the negligence of the discrete effect and the contribution of strain energy to the dislocation energy, the Peierls stress given by the classical Peierls–Nabarro model is about one order of magnitude larger than that given by the improved Peierls–Nabarro model. The result of Peierls stress estimated by the improved Peierls–Nabarro model agrees well with the 2~3 GPa reported in the book of Solid State Physics edited by F. Seitz and D. Turnbull.

Psycholinguistic studies of focus processing have yielded varying results regarding how focus affects language processing. We report the results of an event-related potential (ERP) experiment that used question-answer pairs in a discourse to manipulate whether a target word was contextually focused, contrastively focused, contextually defocused, or contextually neutral. We found a negative-going waveform that was sustained in the time-course (250–800 ms after the target word onset) with a maximum over frontal-central scalp sites. As the structure of the discourse made the target word more focused, the negative-going deflection was systematically reduced. We also observed a frontal positive-going waveform that was larger for the focus-marked words relative to the neutral target word in an earlier time window (150–250 ms, P200), which may reflect increased attention allocated to the focused items. We propose that the reduced negative ERPs for the focused words reflects facilitation of meaning integration when focus functions to establish reference in the discourse representation. This can be attributed to extra attention paid to the focus-marked items that in turn promotes the prominence of focus-marked referent and prompts the contextual priming mechanism that facilitates the access of propositionally relevant items in text memory during reading.

Based on the unique technical characteristics and existing equipment ability of the SDR base station,and the main problems in deploying SDR base station,faced with the network developing environment and operating conditions for operators,the main application scene of SDR base station was put forward,and the new ideas of using GL1800 to construct light-state network in city and county scene were discussed.

The Croatian electricity demand exceeds domestic production and about 30 % of additional power is covered from imports. The Croatian government is planning to add domestic production capacity, using natural gas and coal as the main fuel. Due to the attractive solar irradiation in Croatia, these new projects offer the possibility to build these thermal power plants as hybrid plants by adding solar energy within the production. The present paper will investigate the potential of solar energy in the Southern Croatian region, and its possible contribution in a hybrid set-up. The paper assesses the required input data and presents a hybrid Concentrated Solar Power (CSP)& design. The results demonstrate the potential of adding a CSP in a hybrid power plant in Southern Croatia.

Coal fires are a common and serious problem in most coal-bearing countries. Thus, it is very important to monitor changes in coal fires. Remote sensing provides a useful technique for investigating coal fields at a large scale and for detecting coal fires. In this study, the spreading direction of a coal fire in the Wuda Coal Field (WCF), northwest China, was analyzed using multi-temporal Landsat Thematic Mapper (TM) and Enhanced Thematic Mapper (ETM+) thermal infrared (TIR) data. Using an automated method and based on the land surface temperatures (LST) that were retrieved from these thermal data, coal fires related to thermal anomalies were identified; the locations of these fires were validated using a coal fire map (CFM) that was developed via field surveys; and the cross-validation of the results was also carried out using the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) thermal infrared images. Based on the results from longtime series of satellite TIR data set, the spreading directions of the coal fires were determined and the coal fire development on the scale of the entire coal field was predicted. The study delineated the spreading direction using the results of the coal fire dynamics analysis, and a coal fire spreading direction map was generated. The results showed that the coal fires primarily spread north or northeast in the central part of the WCF and south or southwest in the southern part of the WCF. In the northern part of the WCF, some coal fires were spreading north, perhaps coinciding with the orientation of the coal belt. Certain coal fires scattered in the northern and southern parts of the WCF were extending in bilateral directions. A quantitative analysis of the coal fires was also performed; the results indicate that the area of the coal fires increased an average of approximately 0.101 km2 per year.

Using China’s A-share listed firms from 2007 to 2011, this paper empirically tests how media governance affects firms’ levels of overinvestment and whether external supervision and informal institutional mechanisms reduce these levels. We find that media governance and overinvestment are significantly negatively related. When firms are located in a district with a stronger media governance environment their levels of overinvestment are lower, indicating that media governance significantly restricts overinvestment behavior. When internal corporate governance efficiency is low, the negative relationship between the media environment and overinvestment behavior is significantly enhanced, indicating that when internal governance or formal systems have reduced efficacy, an important complementary role is played by external supervision and the informal institutional environment. After considering endogeneity and different measures of overinvestment and other related variables, the conclusions remain unchanged.

Hydrogen sulfide has been suggested to play an essential role in atherogenesis. There is a paucity of information about the association between H2S and angiotensin converting enzyme 2 (ACE2), a novel homolog of ACE. Therefore, the aim of the study was to explore the role of H2S in atherosclerosis with respect to ACE2 both in vitro and in vivo. Here, a murine model of acutely disturbed flow-induced atherosclerosis by left common carotid artery (LCA) partial ligation was utilized. We found that carotid partial ligation in high-fat fed apoE−/− mice significantly inhibited endogenous H2S synthesis in LCA. Application of NaHS, an H2S donor considerably attenuated the severity of atherosclerosis with upregulating carotid expression of ACE2, thus converting pro-atherosclerotic angiotensin II (Ang II) to anti-atherosclerotic angiotensin 1-7 (Ang-(1-7)). The anti-atherosclerotic effect of NaHS was dramatically abolished by treatment with MLN-4760, an ACE2 inhibitor. In contrast, blockage of H2S formation by DL-propargylglycine exacerbated the burden of atherosclerotic plaques accompanied by inhibiting carotid expression of ACE2. At the cellular level, NaHS dose-dependently promoted the expression of ACE2 and conversion from Ang II to Ang-(1-7) in unstimulated or LPS-stimulated endothelial cells, thus exerting anti-inflammatory properties. The anti-inflammatory effect of NaHS was abrogated by pretreatment with DX600, a selective ACE2 inhibitor. In conclusion, these data provide direct evidences that endogenous H2S insufficiency exists in acute flow disturbance-induced atherosclerosis and that application of H2S may protect against atherosclerosis via upregulating ACE2 expression in endothelial cells.