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Hindlimb ischaemia–reperfusion (IR) is among the most prominent pathophysiological conditions observed in peripheral artery disease (PAD). An exaggerated arterial blood pressure (BP) response during exercise is associated with an elevated risk of cardiovascular events in individuals with PAD. However, the precise mechanisms leading to this exaggerated BP response are poorly elucidated. The P2X3 signalling pathway, which plays a key role in modifying the exercise pressor reflex (EPR), is the focus of the present study. We determined the regulatory role of P2X3 on the EPR in a rat model of hindlimb IR. In vivo and in vitro approaches were used to determine the expression and functions of P2X3 in muscle afferent nerves and EPR in IR rats. We found that in IR rats there was (1) upregulation of P2X3 protein expression in the L4–6 dorsal root ganglia (DRG); (2) amplified P2X currents in isolated isolectin B4 (IB4)‐positive muscle DRG neurons; and (3) amplification of the P2X‐mediated BP response. We further verified that both A‐317491 and siRNA knockdown of P2X3 significantly decreased the activity of P2X currents in isolated muscle DRG neurons. Moreover, inhibition of muscle afferents' P2X3 receptor using A‐317491 was observed to alleviate the exaggerated BP response induced by static muscle contraction and P2X‐induced BP response by α,β‐methylene ATP injection. P2X3 signalling pathway activity is amplified in muscle afferent DRG neurons in regulating the EPR following hindlimb IR. What is the central question of this study?Is the P2X3 signal pathway engaged in the exaggerated exercise pressor reflex (EPR) response in the ischaemia–reperfusion (IR) injury of peripheral artery disease (PAD)?What is the main finding and its importance?IR upregulates expression of the P2X3 receptor and increases the P2X currents in muscle afferent DRG neurons. Pharmacological inhibition using A‐317491 (P2X3 antagonist) and the genetic knockdown of P2X3 reduce the P2X currents in the muscle afferent DRG neurons. A‐317491 also attenuates the exacerbated EPR response following IR.The findings provide evidence that interventions attenuating the P2X3 signalling pathway may enhance tolerance of and adherence to exercise rehabilitation for PAD patients. [ABSTRACT FROM AUTHOR]

This work aims to rapidly detect toxic alkaloids in traditional Chinese medicines (TCM) using laser desorption ionization mass spectrometry (LDI-MS). We systematically investigated twelve nanomaterials (NMs) as matrices and found that MoS2 and defect-rich-WO3 (D-WO3) were the best NMs for alkaloid detection. MoS2 and D-WO3 can be used directly as matrices dipped onto conventional ground steel target plates. Additionally, they can be conveniently fabricated as three-dimensional (3D) NM plates, where the MoS2 or D-WO3 NM is doped into resin and formed using a 3D printing process. We obtained good quantification of alkaloids using a chemothermal compound as an internal standard and detected related alkaloids in TCM extracts, Fuzi (Aconiti Lateralis Radix Praeparata), Caowu (Aconiti Kusnezoffii Radix), Chuanwu (Aconiti Radix), and Houpo (Magnoliae Officinalis Cortex). The work enabled the advantageous "dip and measure" method, demonstrating a simple and fast LDI-MS approach that achieves clean backgrounds for alkaloid detection. The 3D NM plates also facilitated mass spectrometry imaging of alkaloids in TCMs. This method has potential practical applications in medicine and food safety. Doped nanomaterial facilitates 3D printing target plate for rapid detection of alkaloids in laser desorption/ionization mass spectrometry [ABSTRACT FROM AUTHOR]

Proteins and peptides-based therapeutics are making substantial access to the market due to their obvious advantages of strong potency, high specificity and desirable safety profile. However, most clinical products are mainly delivered via parenteral route with inferior convenience. Lung is an attractive non-invasive alternative passage for systemic administration of biologics with numerous outstanding features, as examples of large absorptive surface area, extensive vascularization and mild local microenvironment. Even so, mucociliary clearance, alveolar macrophage phagocytosis, enzymatic metabolism, pulmonary surfactant adsorption and limited epithelium permeability constitute major obstacles affecting the systemic absorption of inhaled proteins and peptides. This article begins by giving a brief overview of challenges for the systemic absorption of inhaled proteins and peptides, and then goes on to a comprehensive review of possible strategies for enhanced pulmonary absorption, including chemical modification, addition of protease inhibitors, incorporation of absorption enhancers, modification with fusion proteins and development of particulate-based drug delivery systems. These strategies can provide enhanced transmembrane absorption capacity while avoiding pulmonary clearance, offering a valuable reference for designing pulmonary delivery systems of protein and peptide drugs. [ABSTRACT FROM AUTHOR]

This study aimed to determine the relationship between bilirubin levels and carotid atherosclerosis (CAS) in the health screening population. After propensity score matching, this retrospective cohort study included 4360 subjects who underwent health examinations regularly in Hebei General Hospital between January 2010 and December 2019 and had no carotid plaque at baseline. After an average follow-up of 26.76 months, the main endpoint Cox regression analysis of carotid plaques was performed. After adjusting the confounding factors, Cox regression analysis showed that when serum total bilirubin (TBIL) and unconjugated bilirubin (UCB) increased by 1 standard deviation (SD), the risk of carotid plaque decreased by 7.30% (95% confidence interval (CI): 2.80–11.60%) and 15.70% (95% CI: 11.40–19.80%), respectively. When conjugated bilirubin (CB) increased by 1 SD, the risk of carotid plaques increased by 24.3% (95% CI: 19.7–29.0%). TBIL and UCB levels were negatively associated with CAS, and CB levels were positively associated with CAS. [ABSTRACT FROM AUTHOR]

Peripheral artery diseases (PAD) increases muscle afferent nerve‐activated reflex sympathetic nervous and blood pressure responses during exercise (termed as exercise pressor reflex). However, the precise signaling pathways leading to the exaggerated autonomic responses in PAD are undetermined. Considering that limb ischemia/reperfusion (I/R) is a feature of PAD, we determined the characteristics of acid‐sensing ion channel (ASIC) currents in muscle dorsal root ganglion (DRG) neurons under the conditions of hindlimb I/R and ischemia of PAD. In particular, we examined ASIC currents in two distinct subpopulations, isolectin B4‐positive, and B4‐negative (IB4+ and IB4−) muscle DRG neurons, linking to glial cell line‐derived neurotrophic factor and nerve growth factor. In results, ASIC1a‐ and ASIC3‐like currents were observed in IB4− muscle DRG neurons with a greater percentage of ASIC3‐like currents. Hindimb I/R and ischemia did not alter the distribution of ASIC1a and ASIC3 currents with activation of pH 6.7 in IB4+ and IB4− muscle DRG neurons; however, I/R altered the distribution of ASIC3 currents in IB4+ muscle DRG neurons with pH 5.5, but not in IB4− neurons. In addition, I/R and ischemia amplified the density of ASIC3‐like currents in IB4− muscle DRG neurons. Our results suggest that a selective subpopulation of muscle afferent nerves should be taken into consideration when ASIC signaling pathways are studied to determine the exercise pressor reflex in PAD. [ABSTRACT FROM AUTHOR]

With the rapid development of biopharmaceuticals and the outbreak of COVID-19, the world has ushered in a frenzy to develop gene therapy. Therefore, therapeutic genes have received enormous attention. However, due to the extreme instability and low intracellular gene expression of naked genes, specific vectors are required. Viral vectors are widely used attributed to their high transfection efficiency. However, due to the safety concerns of viral vectors, nanotechnology-based non-viral vectors have attracted extensive investigation. Still, issues of low transfection efficiency and poor tissue targeting of non-viral vectors need to be addressed. Especially, pulmonary gene delivery has obvious advantages for the treatment of inherited lung diseases, lung cancer, and viral pneumonia, which can not only enhance lung targeting and but also reduce enzymatic degradation. For systemic diseases therapy, pulmonary gene delivery can enhance vaccine efficacy via inducing not only cellular, humoral immunity but also mucosal immunity. This review provides a comprehensive overview of nanocarriers as non-viral vectors of therapeutic genes for enhanced pulmonary delivery. First of all, the characteristics and therapeutic mechanism of DNA, mRNA, and siRNA are provided. Thereafter, the advantages and challenges of pulmonary gene delivery in exerting local and systemic effects are discussed. Then, the inhalation dosage forms for nanoparticle-based drug delivery systems are introduced. Moreover, a series of materials used as nanocarriers for pulmonary gene delivery are presented, and the endosomal escape mechanisms of nanocarriers based on different materials are explored. The application of various non-viral vectors for pulmonary gene delivery are summarized in detail, with the perspectives of nano-vectors for pulmonary gene delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

Bound states of solitons, alias soliton molecules (SMs), are well known in 1D systems, while making stable bound states of multidimensional solitons is a challenging problem because of the underlying instabilities. Here, a scheme for the creation of stable (2+1)D and (3+1)D optical SMs in a gas of cold Rydberg atoms is proposed, in which electromagnetically induced transparency (EIT) is induced by a control laser field. It is shown that, through the interplay of the EIT and the strong long‐range interaction between the Rydberg atoms, the system gives rise to giant nonlocal Kerr nonlinearity, which in turn supports stable (2+1)D spatial optical SMs, as well as ring‐shaped soliton necklaces, including rotating ones. They feature a large size, low generation power, and can be efficiently manipulated by tuning the nonlocality degree of the Kerr nonlinearity. Stable (3+1)D spatiotemporal optical SMs, composed of fundamental or vortex solitons, with low power and ultraslow propagation velocity, can also be generated in the system. These SMs can be stored and retrieved through the switching off and on of the control laser field. The findings reported here suggest applications to data processing and transmission in optical systems. [ABSTRACT FROM AUTHOR]

Background: Medical imaging reports play an important role in communication of diagnostic information between radiologists and clinicians. Head magnetic resonance imaging (MRI) reports can provide evidence that is widely used in the diagnosis and treatment of ischaemic stroke. The high-signal regions of diffusion-weighted imaging (DWI) images in MRI reports are key evidence. Correctly identifying high-signal regions of DWI images is helpful for the treatment of ischaemic stroke patients. Since most of the multiple signals recorded in head MRI reports appear in the same part, it is challenging to identify high-signal regions of DWI images from MRI reports.Methods: We developed a deep learning model to automatically identify high-signal regions of DWI images from head MRI reports. We proposed a fine-grained entity typing model based on machine reading comprehension that transformed the traditional two-step fine-grained entity typing task into a question-answering task.Results: To prove the validity of the model proposed, we compared it with the fine-grained entity typing model, of which the F1 measure was 5.9% and 3.2% higher than the F1 measures of the models based on LSTM and BERT, respectively.Conclusion: In this study, we explore the automatic identification of high-signal regions of DWI images from the description part of a head MRI report. We transformed the identification of high-signal regions of DWI images to an FET task and proposed an MRC-FET model. Compared with the traditional two-step FET method, the model we proposed not only simplifies the task but also has better performance. The comparable result shows that the work in this study can contribute to improving the clinical decision support system. [ABSTRACT FROM AUTHOR]

National music is a treasure of Chinese traditional culture. It contains the cultural characteristics of various regions and reflects the core value of Chinese traditional culture. Classification technology classifies a large number of unorganized drama documents, which are not labeled, and to some extent, it helps folk music better enter the lives of ordinary people. Simulate folk music of different spectrum and record corresponding music audio under laboratory conditions Through Fourier transform and other methods, music audio is converted into spectrogram, and a total of 2608 two-dimensional spectrogram images are obtained as datasets. The sonogram dataset is imported into the deep convolution neural network GoogLeNet for music type recognition, and the test accuracy is 99.6%. In addition, the parallel GoogLeNet technology based on inverse autoregressive flow is used. The unique improvement is that acoustic features can be quickly converted into corresponding speech time-domain waveforms, reaching the real-time level, improving the efficiency of model training and loading, and outputting speech with higher naturalness. In order to further prove the reliability of the experimental results, the spectrogram datasets are imported into Resnet18 and Shufflenet for training, and the test accuracy of 99.2% is obtained. The results show that this method can effectively classify and recognize music. The experimental results show that this scheme can achieve more accurate classification. The research realizes the recognition of national music through deep learning spectrogram classification for the first time, which is an intelligent and fast new method of classification and recognition. [ABSTRACT FROM AUTHOR]

Sympathetic nerve activity (SNA) regulates the contraction of vascular smooth muscle and leads to a change in arterial blood pressure (BP). It was observed that SNA, vascular contractility, and BP are heightened in patients with peripheral artery disease (PAD) during exercise. The exercise pressor reflex (EPR), a neural mechanism responsible for BP response to activation of muscle afferent nerve, is a determinant of the exaggerated exercise-induced BP rise in PAD. Based on recent results obtained from a series of studies in PAD patients and a rat model of PAD, this review will shed light on SNA-driven BP response and the underlying mechanisms by which receptors and molecular mediators in muscle afferent nerves mediate the abnormalities in autonomic activities of PAD. Intervention strategies, particularly non-pharmacological strategies, improving the deleterious exercise-induced SNA and BP in PAD, and enhancing tolerance and performance during exercise will also be discussed. [ABSTRACT FROM AUTHOR]

We propose and numerically investigate an angle-tuned polarization-independent multi-narrowband perfect absorber, which comprises a simple gold nanocube array on SiO2/oxidized aluminum mirror layers. The oxidized aluminum mirror is able to support the surface plasmon polariton mode on the SiO2/Al2O3 interface. The multi-narrowband absorption contributes to the simultaneously excited quasi-metalâ€"insulatorâ€"metal guided modes and standing wave cavity mode in the thick insulator layer by the incident light normal to the structure in the wavelength range 1400â€"2400 nm. Moreover, the absorption can be actively modulated by adjusting the incidence angle, and it is polarization independent. The perfect absorber is also suitable for sensing, with the figure of merit reaching 102 RIUâˆ'1 within the refractive index range from 1.3 to 1.36. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of 68 Ga-PSMA-11 positron emission tomography/computerized tomography (PET/CT) in evaluating lacrimal and salivary glands function. Methods: Ten patients with pSS and 18 healthy volunteers were recruited in this study. All participants underwent 68 Ga-PSMA-11 PET/CT, and the patients with pSS performed salivary gland scintigraphy the next day. The maximum standardized uptake value (SUVmax), average of the standard uptake value (SUVavg), the average CT value (CTavg), and volume (V) in the region of interest (ROI) of each lacrimal and salivary gland were analyzed in68Ga-PSMA-11 PET/CT. The uptake ratio (UR) of the bilateral parotid gland and submandibular gland was calculated in salivary gland scintigraphy (SGS). Statistical analysis was processed by the SPSS software and the MedCalc software. A p-value of < 0.05 was considered as statistically significant. Results: Almost all the parameters of pSS were significantly lower than those of the control group (p < 0.05). The left parotid gland (PG) UR was positive correlation with left PG SUVmax (r = 0.758, p = 0.011) and left PG SUVavg (r = 0.770, p = 0.009); the right PGUR was positive correlation with right PG SUVmax (r = 0.721, p = 0.019) and right PG SUVavg (r = 0.721, p = 0.019). The SUVmax and SUVavg of both sides of acrimal and salivary glands had area under the receiver operating curve values greater than 0.5. Conclusions: 68 Ga-PSMA-11 PET/CT can simultaneously enable the visualization of lacrimal glands and salivary glands and be used to evaluate the lacrimal and salivary glands function. Key Points • We have firstly investigated the value of 68 Ga-PSMA-11 PET/CT in evaluating lacrimal and salivary glands function in patients with pSS 68 Ga-PSMA-11 PET/CT can simultaneously allow the visualization of lacrimal glands and salivary glands. • The results of the present study imply that 68 Ga-PSMA-11 PET/CT can be used to evaluate the lacrimal and salivary glands function in patients with pSS meanwhile. [ABSTRACT FROM AUTHOR]

Objectives: To compare the predictive ability of six pre-endoscopic scoring systems (ABC, AIMS65, GBS, MAP(ASH), pRS, and T-score) for outcomes of upper gastrointestinal bleeding (UGIB) in elderly and younger patients.Methods: A retrospective study of 1260 patients, including 530 elderly patients (age [Formula: see text] 65) and 730 younger patients (age < 65) presenting with UGIB, was performed at Zhongda Hospital Southeast University, from January 2015 to December 2020. Six scoring systems were used.Results: ABC had the largest areas under the curve (AUCs) of 0.827 (0.792-0.858), and 0.958 (0.929-0.987) for elderly and younger groups for predicting mortality respectively. The differences of the AUCs for predicting the outcome of mortality and rebleeding between the two groups were significant for ABC and pRS (p < 0.01). For intervention prediction, significant differences were observed only for pRS [AUC 0.623 (0.578-0.669) vs. 0.699 (0.646-0.752)] (p < 0.05) between the two groups. For intensive care unit (ICU) admission, the AUC for MAP (ASH) [0.791 (0.718-0.865) vs. 0.891 (0.831-0.950)] and pRS [0.610 (0.514-0.706) vs. 0.891 (0.699-0.865)] were more effective for the younger group (p < 0.05 and p < 0.01, respectively). For comparison of scoring systems in the same cohort, ABC was significantly higher than pRS: AUC 0.710 (0.699-0.853, p < 0.05) and T-score 0.670 (0.628-0.710, p < 0.01) for predicting mortality in the elderly group. In the younger group, ABC was significantly higher than GBS and T-score (p < 0.01). MAP(ASH) performs the best in predicting intervention in both groups.Conclusions: ABC and pRS are more accurate for predicting mortality and rebleeding in the younger cohort, and pRS may not be suitable for elderly patients. There was no difference between the two study populations for GBS, AIMS65, and T-score. Except for ICU admission, MAP(ASH) showed fair accuracy for both cohorts. [ABSTRACT FROM AUTHOR]

The heterogeneous Fenton-like reaction has been receiving increasing attention for its inexpensiveness and high efficiency in water treatment. In this study, a novel strategy was proposed for preparing spherical ZVI/Mn-C bimetallic catalysts with a high activity for a Fenton-like reaction by using the ammonium alginate assisted sol–gel method coupled with a carbothermic reduction. The results showed that the obtained ZVI/Mn-C spheres had a uniform size, smooth surface and good sphericity, and the particle size of ZVI was limited to about 30 nm by the carbon layer. Among all catalysts, the ZVI/Mn-C-31 catalyst exhibited the highest phenol degradation efficiency in the Fenton-like process, and almost 100% phenol degradation efficiency was achieved under neutral pH at room temperature within 5 min. Moreover, the ZVI/Mn-C-31/H2O2 system showed a 100% degradation efficiency for removing a wide range of aromatic pollutants, including catechol, resorcinol and o-nitrophenol. Moreover, the radicals-scavenging experiment illustrated that the ·OH played a key factor in mineralizing the organic matters, and the ·O2− generated from the MnO-H2O2 system accelerated the conversion rate of ferric iron to ferrous iron. Due to the synergistic effects between ZVI and MnO, the ZVI/Mn-C-31 catalyst performed excellently in the Fenton-like reaction at an extended pH range. [ABSTRACT FROM AUTHOR]

In this work, the corrosion behaviors of as-plasma sprayed Yb 2 SiO 5 and LaMgAl 11 O 19 coatings under an environment with a volumetric ratio of 90% H 2 O-10% O 2 were investigated at 1300 °C. The results showed that Yb 2 SiO 5 and LaMgAl 11 O 19 coatings had good water vapor corrosion resistance. Therefore, Si/Yb 2 SiO 5 /LaMgAl 11 O 19 tri-layer EBCs were designed and prepared to completely cover the surface of SiC f /SiC by using atmospheric plasma spraying (APS). The water vapor corrosion behaviors of SiC f /SiC with and without EBCs at 1300 °C were investigated. The results showed that tri-layer coating can provide better corrosion resistance for SiC f /SiC at a high-temperature steam environment at 1300 °C. By comparing the water vapor corrosion behaviors of single-layer coatings and the tri-layer EBCs under same corrosion environment, it was found that the thermal mismatch stress and the formation of TGO is the main causes of tri-layer coating failure. [ABSTRACT FROM AUTHOR]

Thyroid cancer (TC) is one of the widely diagnosed carcinomas in women before the age of 30. Nevertheless, there is currently a lack of specific biomarkers for predicting the prognosis of TC. Long noncoding RNAs (lncRNAs) were important regulators in human cancer progression as previously described. Unfortunately, there is little known on these lncRNAs' functions and molecular mechanisms in TC. In our literature, we found that LOC554202 (MIR31HG) was upregulated in TC samples and correlated with clinicopathological features, including M stage, N stage, and lymph nodes examined status in TC. In addition, we found that LOC554202 overexpression was evidently correlated with high immune infiltrate levels of CD8+ T cells, macrophage, neutrophil, myeloid dendritic cells, and B cells in TC. Knockdown of LOC554202 impeded TC cell proliferation and cycle progression. We found that LOC554202 had an association with metabolic pathways, vesicle-mediated transport, tricarboxylic acid cycle, Hedgehog signaling pathway, and Hippo signaling pathway in TC. Reducing LOC554202 hindered TC cell proliferation and cycle progression. Finally, we found that LOC554202 participated in modulating the expression of the regulators of Hippo signaling and TCA pathway, such as CCND2, CCND3, SDHC, SDHD, SUCLA2, and SUCLG1. We thought that this study would largely enhance our understanding of LOC554202's functional roles in human TC progression and immune response. [ABSTRACT FROM AUTHOR]

Objective: This study aims to prepare candidate vaccines for cervical cancer immunotherapy by inserting the fused genes of human papillomavirus (HPV)16/18/58 mE6E7 lacking transforming activity into an adenovirus vector and to verify its efficiency in model mice with tumor expressing the associated HPV genes. Methods: The E6/E7 genes of HPV16/18/58 were point-mutated to abolish their transforming activity, and adenovirus (AD)-HPV16/18/58 mE6E7 adenovirus vaccine was constructed. The immune effect of the adenovirus vaccine against HPV16/18/58-type tumors was analyzed by tumor morphology, enzyme linked immunosorbent assay, enzyme-linked immunospot and specific cytotoxic T lymphocyte (CTL) and T lymphocyte subsets. Results: The HPV16/18/58 mE6E7 plasmid containing point mutations was verified by quantitative real-time polymerase chain reaction (qRT-PCR), enzyme digestion and electrophoresis, and gene sequencing. qRT-PCR and Western blots verified that AD-HPV16/18/58 mE6E7 could express the HPV16 mE6E7, HPV18 mE6E7 and HPV58 mE6E7 fusion genes and proteins in cells. The results of animal experiments were as follows: In the vaccine group, the tumors formed later, the incubation period was longer, the growth was slower, growth was inhibited, and the survival period was significantly prolonged. The immunological results all showed that the vaccine could induce effective humoral and cellular immunity in mice with three types of tumors, compared with the phosphate buffered saline (PBS) group and the adenovirus-negative control (AD-NC) group, the differences were statistically significant (P < 0.05). Conclusion: We successfully constructed the HPV16/18/58 trivalent therapeutic adenovirus vaccine AD-HPV16/18/58 mE6E7. The AD-HPV16/18/58 mE6E7 adenovirus vaccine can protect immunized mice to a certain extent from TC-1, U14/LV-HPV18 E6E7 and U14/LV-HPV58 E6E7 cells, which contain HPV16, 18 and 58 E6 and/or E7 genes, respectively. [ABSTRACT FROM AUTHOR]

Nesfatin-1 is a neuropeptide produced in the hypothalamus. It is known that Nesfatin-1 is involved in food uptake, fat storage, and other metabolic regulation. We hypothesized that Nesfatin-1 may play a role in cardiovascular tissue. Free fatty acids (FFAs) are known to be the risk factor for cardiovascular diseases. FFA-mediated endothelial dysfunction is the critical mechanism of many cardiovascular disorders. The present study explores the protective effects of Nesfatin-1 on FFA-induced endothelial inflammation and the underlying mechanism. We found that significantly increased lactate dehydrogenase release and production of inflammatory factors were observed in FFA-treated human aortic endothelial cells (HAECs), accompanied by the enhanced attachment of U937 monocytes to HAECs and upregulated cell adhesion molecule vascular cell adhesion molecule-1, which were dramatically reversed by the treatment with Nesfatin-1. In addition, the promoted level of nuclear regulator NF-κB p65 and transcriptional function of NF-κB in FFA-treated HAECs were greatly suppressed by HAECs. Growth Factor Independent 1 Transcriptional Repressor 1 (Gfi1), an important negative regulator of NF-κB activity, was significantly downregulated in HAECs by FFAs and was upregulated by Nesfatin-1. Lastly, the inhibitory effects of Nesfatin-1 against FFA-induced NF-κB activation and adhesion of U937 monocytes to HAECs were abolished by the knockdown of Gfi1. In conclusion, our data reveal that Nesfatin-1 inhibited FFA-induced endothelial inflammation mediated by the Gfi1/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

C-type lectins (CTLs) are important immune molecules in innate immune, which participate in non-self recognition and clearance of pathogens. Here, a new CTL with two distinct C-type lectin domains (CTLDs) from Pacific white shrimp Penaeus vannamei , designated as PvMR1 was identified. The obtained PvMR1 coding sequence (CDS) was 1044 bp long encoding a protein with 347 amino acids. PvMR1 had two CTLD, a conserved mannose-specific EPN motif and a galactose-specific QPD motif, clustering into the same branch as the crustacean CTLs. PvMR1 was widely distributed in shrimp tissues with the highest transcription level in the hepatopancreas, with significantly induced mRNA expression on the hepatopancreas and intestines after immune challenge with Vibrio anguillarum. In vitro assays with recombinant PvMR1 (rPvMR1) protein revealed that it exhibited a wide range of antimicrobial activity, bacterial binding ability, and bacterial agglutination activity in a Ca2+-independent manner. Moreover, PvMR1 promoted bacterial phagocytosis in hemocytes. Furthermore, rPvMR1 treatment could significantly enhance the bacterial clearance in hemolymph and greatly improved the survival of shrimp under V. anguillarum infection in vivo. These results collectively suggest that PvMR1 plays an important role in antibacterial immune response of P. vannamei. • In this study, a new CTL with two distinct C-type lectin domains (CTLDs) from Penaeus vannamei , designated as PvMR1 was identified. • The observations indicated that PvMR1 plays an important role in innate immune responses of Penaeus vannamei. • Considering that PvMR1 functioned as a pattern recognition receptor that participates in innate immunity, we suggest that consideration for the strategies used to control Penaeus vannamei aquaculture disease. [ABSTRACT FROM AUTHOR]

Key points: During exercise, bradykinin (BK), a muscle metabolite in ischaemic muscles, exaggerates autonomic responses to activation of muscle afferent nerves in peripheral artery disease (PAD).We examined whether BK inhibits activity of KV4 channels in muscle afferent neurons of PAD rats induced by femoral artery occlusion.We demonstrated that: 1) femoral occlusion attenuates KV4 currents in dorsal root ganglion (DRG) neurons innervating the hindlimb muscles and decreases the threshold of action potential firing; 2) BK has a greater inhibitory effect on KV4 currents in muscle DRG neurons of PAD rats; and 3) expression of KV4.3 is downregulated in DRGs of PAD rats and inhibition of KV4.3 significantly decreases activity of KV4 currents in muscle DRG neurons.Femoral artery occlusion‐induced limb ischaemia and/or ischaemia‐induced metabolites (i.e. BK) inhibit activity of KV4 channels in muscle afferent neurons and this is likely involved in the exaggerated exercise pressor reflex in PAD. Muscle afferent nerve‐activated reflex sympathetic nervous and blood pressure responses are exaggerated during exercise in patients with peripheral artery diseases (PAD) and in PAD rats induced by femoral artery occlusion. However, the precise signalling pathways and molecular mediators responsible for these abnormal autonomic responses in PAD are poorly understood. A‐type voltage‐gated K+ (KV) channels are quintessential regulators of cellular excitability in the various tissues. Among KV channels, KV4 (i.e. KV4.1 and KV4.3) in primary sensory neurons mainly participate in physiological functions in regulation of mechanical and chemical sensation. However, little is known about the role of KV4 in regulating neuronal activity in muscle afferent neurons of PAD. In addition, bradykinin (BK) is considered as a muscle metabolite contributing to the exaggerated exercise pressor reflex in PAD rats with femoral artery occlusion. Our data demonstrated that: 1) KV4 currents are attenuated in dorsal root ganglion (DRG) neurons innervating the hindlimb muscles of PAD rats, along with a decreasing threshold of action potential firing; 2) KV4 currents are inhibited by application of BK onto muscle DRG neurons of PAD rats to a greater degree; and 3) expression of KV4.3 is downregulated in the DRGs of PAD rats and KV4.3 channel is a major contributor to the activity of KV4 currents in muscle DRG neurons. In conclusion, data suggest that femoral artery occlusion‐induced limb ischaemia and/or ischaemia‐induced metabolites (i.e. BK) inhibit the activity of KV4 channels in muscle afferent neurons likely leading to the exaggerated exercise pressor reflex observed in PAD. Key points: During exercise, bradykinin (BK), a muscle metabolite in ischaemic muscles, exaggerates autonomic responses to activation of muscle afferent nerves in peripheral artery disease (PAD).We examined whether BK inhibits activity of KV4 channels in muscle afferent neurons of PAD rats induced by femoral artery occlusion.We demonstrated that: 1) femoral occlusion attenuates KV4 currents in dorsal root ganglion (DRG) neurons innervating the hindlimb muscles and decreases the threshold of action potential firing; 2) BK has a greater inhibitory effect on KV4 currents in muscle DRG neurons of PAD rats; and 3) expression of KV4.3 is downregulated in DRGs of PAD rats and inhibition of KV4.3 significantly decreases activity of KV4 currents in muscle DRG neurons.Femoral artery occlusion‐induced limb ischaemia and/or ischaemia‐induced metabolites (i.e. BK) inhibit activity of KV4 channels in muscle afferent neurons and this is likely involved in the exaggerated exercise pressor reflex in PAD. [ABSTRACT FROM AUTHOR]

Interleukin‐6 (IL‐6) via trans‐signaling pathway plays a role in modifying muscle sensory nerve‐exaggerated exercise pressor reflex in rats with ligated femoral arteries, but the underlying mechanisms are poorly understood. It is known that voltage‐gated potassium channel subfamily member Kv4 channels contribute to the excitabilities of sensory neurons and neuronal signaling transduction. Thus, in this study, we determined that 1) IL‐6 regulates the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD) induced by femoral artery ligation and 2) Kv4 channels in muscle dorsal root ganglion (DRG) neurons are engaged in the role played by IL‐6 trans‐signaling pathway. We found that the protein levels of IL‐6 and its receptor IL‐6R expression were increased in the DRGs of PAD rats with 3‐day of femoral artery occlusion. Inhibition of muscle afferents' IL‐6 trans‐signaling pathway (gp130) by intra‐arterial administration of SC144, a gp130 inhibitor, into the hindlimb muscles of PAD rats alleviated blood pressure response to static muscle contraction. On the other hand, we found that 3‐day femoral occlusion decreased amplitude of Kv4 currents in rat muscle DRG neurons. The homo IL‐6/IL‐6Rα fusion protein (H. IL‐6/6Rα), but not IL‐6 alone significantly inhibited Kv4 currents in muscle DRG neurons; and the effect of H. IL‐6/6Rα was largely reverted by SC144. In conclusion, our data suggest that via trans‐signaling pathway upregulated IL‐6 in muscle afferent nerves by ischemic hindlimb muscles inhibits the activity of Kv4 channels and thus likely leads to adjustments of the exercise pressor reflex in PAD. [ABSTRACT FROM AUTHOR]

Hypoxia‐inducible factor 1α (HIF‐1α) is a transcription factor mediating adaptive responses to hypoxia and ischemia. Our previous work showed that HIF‐1α is increased in muscle sensory nerves of rats with peripheral artery disease (PAD) induced by femoral artery occlusion. The present study was further to examine the role played by HIF‐1α in regulating the response of arterial blood pressure (BP) to the activation of muscle afferent nerve during static muscle contraction in rats with femoral artery occlusion. A rat model of femoral artery ligation was used to study PAD in this study. Western blot analysis was employed to examine the protein levels of HIF‐1α in the dorsal root ganglion (DRG) tissues. BAY87, a synthesized compound with the characteristics of highly potent and specific suppressive effects on expression and activity of HIF‐1α, was given into the arterial blood supply of the ischemic hindlimb muscles before the exercise pressor reflex was evoked by static muscle contraction. First, HIF‐1α was increased in the DRG of occluded limbs (optical density: 0.89 ± 0.13 in control versus 1.5 ± 0.05 in occlusion; p < 0.05, n = 6 in each group). Arterial injection of BAY87 (0.2 mg/kg) then inhibited expression of HIF‐1α in the DRG of occluded limbs 3 hr following its injection (optical density: 1.02 ± 0.09 in occluded limbs with BAY87 versus 1.06 ± 0.1 in control limbs; p > 0.05, n = 5 in each group). In addition, muscle contraction evoked a greater increase in BP in occluded rats. BAY87 attenuated the enhanced BP response in occluded rats to a greater degree than in control rats. Our data suggest that the inhibition of HIF‐1α alleviates the exaggeration of the exercise pressor reflex in rats under ischemic circumstances of the hindlimbs in PAD induced by femoral artery occlusion. [ABSTRACT FROM AUTHOR]

Depression is a complex psychiatric disorder. Previous studies have shown that running exercise reverses depression-like behavior faster and more effectively than fluoxetine therapy. GABAergic interneurons, including the PV+ interneuron subtype, in the medial prefrontal cortex (MPFC) are involved in pathological changes of depression. It was unknown whether running exercise and fluoxetine therapy reverse depression-like behavior via GABAergic interneurons or the PV+ interneurons subtype in MPFC. To address this issue, we subjected mice with chronic unpredictable stress (CUS) to a 4-week running exercise or fluoxetine therapy. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that running exercise enriched GABAergic synaptic pathways in the MPFC of CUS-exposed mice. However, the number of PV+ interneurons but not the total number of GABAergic interneurons in the MPFC of CUS-exposed mice reversed by running exercise, not fluoxetine therapy. Running exercise increased the relative gene expression levels of the PV gene in the MPFC of CUS-exposed mice without altering other subtypes of GABAergic interneurons. Moreover, running exercise and fluoxetine therapy both significantly improved the length, area and volume of dendrites and the spine morphology of PV+ interneurons in the MPFC of mice exposed to CUS. However, running exercise but not fluoxetine therapy improved the dendritic complexity level of PV+ interneurons in the MPFC of CUS-exposed mice. In summary, the number and dendritic complexity level of PV+ interneurons may be important therapeutic targets for the mechanism by which running exercise reverses depression-like behavior faster and more effectively than fluoxetine therapy. • Runing exercise improved depression-like behavior faster and more comprehensively in CUS-exposed mice than fluoxetine therapy. • The number of PV+ interneurons rather than the total number of GABAergic neurons in the MPFC was increased by running exercise but not fluoxetine therapy. • Runing exercise, but not fluoxetine therapy, reversed the complexity levels of PV+ interneuron dendrites in the MPFC of CUS-exposed mice. [ABSTRACT FROM AUTHOR]

Sustained drug delivery is considered as an effective strategy to improve the treatment of local lung diseases. In this context, inhalation administration of large porous microparticles (LPPs) represents promising prospects. However, one major challenge with said delivery technology is to control the drug release pattern (especially to decrease the burst release) while maintaining a low mass density/high porosity, which is of high significance for the aerodynamic behavior of LPP systems. Here, we show how to engineer drug-loaded, biodegradable LPPs with varying microstructure by means of a premix membrane emulsification-solvent evaporation (PME-SE) method using poly(vinyl pyrrolidone) (PVP) as the pore former. The influence of PVP concentration on the physicochemical properties, in-vitro drug release behavior and in-vitro aerodynamic performance of the drug-loaded microparticles was tested. We demonstrated that the PME-SE technique led to LPPs with favorable pore distribution characteristics (i.e., low external but high internal porosity) as a function of the PVP concentration. In general, more PVP conditioned a larger discrepancy of the internal vs. external porosity. When the external porosity of the LPP formulation (15% of PVP during the manufacturing process) was less than 3%, the burst release of the embedded drug was significantly reduced compared to LPPs prepared by a "conventional" emulsification solvent evaporation method. All the formulations prepared by the PME-SE method had aerodynamic properties suitable for inhalation. This is the first report indicating that the microstructure of LPPs can be tailored using the PME-SE technology with PVP as a suitable pore former. Doing so, we designed LPP formulations having full control over the drug release kinetics and aerodynamic behavior. [ABSTRACT FROM AUTHOR]

Na0.5Bi4.5‐xCexTi4O15 (x = 0, 0.02, 0.04, 0.06, 0.08, 0.10) lead‐free piezoelectric ceramics with high Curie temperatures are fabricated using the conventional solid‐phase method. The effects of the Ce content on the phase structures, morphologies, and electrical properties of the Na0.5Bi4.5‐xCexTi4O15 ceramics are systematically investigated. The appropriate content of Ce increases b/a and c/a and induces the distortion of the crystal structure. The increased b/a leads to a transverse asymmetry of the Na0.5Bi4.5‐xCexTi4O15 ceramics, which facilitates the dipole flipping, thus enhancing the piezoelectric properties (d33 = 20 pC/N). Although the improved c/a increases the degree of tetragonality of the Na0.5Bi4.5‐xCexTi4O15 ceramic, which decreases the Curie temperature (TC), the TC values of all samples are higher than 600°C, considerably higher than the practical application temperature. The Ce doping significantly reduces the dielectric loss of the sample and increases its dielectric performance. The improvements in electric properties by the cerium doping can expand its use in high‐temperature environments for oilfield logging, aerospace, and military applications. [ABSTRACT FROM AUTHOR]

Searching similar graphs in graph databases for a query graph has attracted extensive attention recently. Existing works on graph similarity queries are threshold based approaches which return graphs with distances to the query smaller than a given threshold. However, in many applications the number of answer graphs for the same threshold can vary significantly for different queries. In this paper, we study the problem of finding top- $k$ k most similar graphs for a query under the distance measure based on maximum common subgraph (MCS). Since computing MCS is NP-hard, we devise a novel framework to prune unqualified graphs based on the lower bounds of graph distance, and accordingly derive four lower bounds with different tightness and computational cost for pruning. To further reduce the number of MCS computations, we also propose an improved framework based on both lower and upper bounds, and derive three new upper bounds. To support efficient pruning, we design three indexes with different tradeoffs between pruning power and construction cost. To accelerate the index construction, we explore bound relaxation techniques, based on which approximate indexes can be efficiently built. We conducted extensive performance studies on real-life graph datasets to validate the effectiveness and efficiency of our approaches. [ABSTRACT FROM AUTHOR]

Background: Cardiogenic stroke has increasing morbidity in China and brought economic burden to patient families. In cardiogenic stroke diagnosis, echocardiograph examination is one of the most important examinations. Sonographers will investigate patients' heart via echocardiograph, and describe them in the echocardiograph reports. In this study, we developed a machine learning model to automatically identify diagnosis evidences of cardiogenic stroke providing to neurologist for clinical decision making.Methods: We collected 4188 Chinese echocardiograph reports of 4018 patients, with average length 177 Chinese characters in free-text style. Collaborating with neurologists and sonographers, we summarized 149 phrases on diagnosis evidence of cardiogenic stroke such as "" (severe mitral stenosis), "" (aortic valve degeneration) and so on. Furthermore, we developed an annotated corpus via mapping 149 phrases to the 4188 reports. We selected 11 most frequent diagnosis evidence types such as "" (mitral stenosis) for further identifying. The generated corpus is divided into training set and testing set in the ratio of 8:2, which is used to train and validate a machine learning model to identify the evidence of cardiogenic stroke using BiLSTM-CRF algorithm.Results: Our machine learning method achieved the average performance on the diagnosis evidence identification is 98.03, 90.17 and 93.94% respectively. In addition, our method is capable to identify the novel diagnosis evidence of cardiogenic stroke description such as "-" (mitral stenosis), "" (aortic valve calcification) et al. CONCLUSIONS: In this study, we analyze the structure of the echocardiograph reports and summarized 149 phrases on diagnosis evidence of cardiogenic stroke. We use the phrases to generate an annotated corpus automatically, which greatly reduces the cost of manual annotation. The model trained based on the corpus also has a good performance on the testing set. The method of automatically identifying diagnosis evidence of cardiogenic stroke proposed in this study will be further refined in the practice. [ABSTRACT FROM AUTHOR]

Faced with the threat of lung cancer-related deaths worldwide, small interfering RNA (siRNA) can silence tumor related messenger RNA (mRNA) to tackle the issue of drug resistance with enhanced anti-tumor effects. However, how to increase lung tumor targeting and penetration with enhanced gene silencing are the issues to be addressed. Thus, the objective of this study is to explore the feasibility of designing non-viral siRNA vectors for enhanced lung tumor therapy via inhalation. Here, shell-core based polymer-lipid hybrid nanoparticles (HNPs) were prepared via microfluidics by coating PLGA on siRNA-loaded cationic liposomes (Lipoplexes). Transmission electron microscopy and energy dispersive spectroscopy study demonstrated that HNP consists of a PLGA shell and a lipid core. Atomic force microscopy study indicated that the rigidity of HNPs could be well tuned by changing thickness of the PLGA shell. The designed HNPs were muco-inert with increased stability in mucus and BALF, good safety, enhanced mucus penetration and cellular uptake. Crucially, HNP1 with the thinnest PLGA shell exhibited superior transfection efficiency (84.83%) in A549 cells, which was comparable to that of lipoplexes and Lipofectamine 2000, and its tumor permeability was 1.88 times that of lipoplexes in A549-3T3 tumor spheroids. After internalization of the HNPs, not only endosomal escape but also lysosomal exocytosis was observed. The transfection efficiency of HNP1 (39.33%) was 2.26 times that of lipoplexes in A549-3T3 tumor spheroids. Moreover, HNPs exhibited excellent stability during nebulization via soft mist inhaler. In conclusion, our study reveals the great potential of HNP1 in siRNA delivery for lung cancer therapy via inhalation. [Display omitted] [ABSTRACT FROM AUTHOR]

For time immemorial, Chinese herbal medicines (CHMs) have been widely used in China for disease treatment and promotion of general well-being. However, in recent years, many studies have shown that mycotoxins produced by fungi could contaminate CHMs due to unfavourable pre- or post-harvest conditions, raising major concern for consumer safety. At present, there is a significant focus on developing novel mycotoxin detection methods for analysing CHMs, and numerous studies have aimed to determine which kinds of raw herbal materials are most susceptible to mycotoxin contamination. In this review, we focus on recent advances in understanding and detection of mycotoxins in domestic raw herbal materials and related products from 2000 to 2018. Aspects of mycotoxin contamination of CHMs covered in this review include common mycotoxin contaminants in CHMs, maximum mycotoxin residue limits, analytical methods for mycotoxin detection and their applications and limitations, as well as a brief discussion of the trends in ongoing research. [ABSTRACT FROM AUTHOR]

Housefly larvae are widely used in livestock breeding industry as a functional feed additive with immunostimulant properties, but their effects as dietary additive are poorly understood in aquatic animals. We conducted an eight‐week rearing experiment to determine the effects of housefly larvae (complete) on growth performance, immunity and intestinal microbiota in swamp eel (Monopterus albus). Dietary treatments were as follows: BD (control group, fed a basal diet), FL7 (fly larvae supplemented once weekly, i.e., 6‐day basal diet, 1‐day larvae) and FL3 (larvae supplemented every third day, i.e., 2‐day basal diet, 1‐day larvae). The final body weight (FBW) and weight gain (WG) of the FL3 group significantly (p <.05) increased. Hepatosomatic index (HSI) and malondialdehyde (MDA) concentration significantly decreased in FL3 and FL7 groups. The expression of immune‐related genes was also influenced by the fly larvae. Aeromonas hydrophila challenge experiment produced higher survival rates in the FL3 (75%) and FL7 (37.5%) groups. Fly larvae also affected the composition of gut microbiota: the abundance of Bacteroides increased, and Pseudomonas decreased, in the treatment groups. Dietary supplementation of housefly larvae has positive effects on the growth and immunity of swamp eel, and we suggest supplementing housefly larvae every third day. [ABSTRACT FROM AUTHOR]

Background: Immune cell infiltration in the tumor microenvironment (TME) affects tumor initiation, patients' prognosis and immunotherapy strategies. However, their roles and interactions with genomics and molecular processes in hepatocellular carcinoma (HCC) still have not been systematically evaluated. Methods: We performed unsupervised clustering of total 1000 HCC samples including discovery and validation group from available public datasets. Immune heterogeneity of each subtype was explored by multi-dimension analysis. And a support vector machine (SVM) model based on multi-omics signatures was trained and tested. Finally, we performed immunohistochemistry to verify the immune role of signatures. Results: We defined three immune subtypes in HCC, with diverse clinical, molecular, and genomic characteristics. Cluster1 had worse prognosis, better anti-tumor characteristics and highest immune scores, but also accompanied by immunosuppression and T cell dysfunction. Meanwhile, a better anti-PD1/CTLA4 immunotherapeutic response was predicted in cluster1. Cluster2 was enriched in TAM-M2 and stromal cells, indicating immunosuppression. Cluster3, with better prognosis, had lowest CD8 T cell but highest immune resting cells. Further, based on genomic signatures, we developed an SVM classifier to identify the patient's immunological status, which was divided into Type A and Type B, in which Type A had poorer prognosis, higher T cell dysfunction despite higher T cell infiltration, and had better immunotherapeutic response. At the same time, MMP9 may be a potential predictor of the immune characteristics and immunotherapeutic response in HCC. Conclusions: Our work demonstrated 3 immune clusters with different features. More importantly, multi-omics signatures, such as MMP9 was identified based on three clusters to help us recognize patients with different prognosis and responses to immunotherapy in HCC. This study could further reveal the immune status of HCC and provide potential predictors for immune checkpoint treatment response. [ABSTRACT FROM AUTHOR]

Key points: During exercise, the blood pressure (BP) response is exaggerated in peripheral artery disease (PAD).We examined whether heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in PAD rats.With HT (increase in basal muscle temperature of ∼1.5°C for 30 min, twice daily for three continuous days), the amplified BP response to muscle contraction is alleviated in PAD.We demonstrated that HT attenuates the enhancement of the BP response induced by stimulation of P2X in muscle afferent nerves of PAD rats. HT also attenuates the upregulation of the P2X3 and the increase in P2X currents in the muscle afferent neurons of PAD rats.Previous heat exposure plays a beneficial role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction in the activity of the P2X receptor pathway is probably a part of the mechanism mediating this improvement. The current study was performed to examine if heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD). We further determined if the temperature‐sensitive P2X receptor is involved in the effects of HT. The pressor response to static muscle contraction and α,β‐methylene ATP (αβ‐me ATP, a P2X agonist) was examined. Western blot analysis was used to determine the protein levels of P2X3 in the dorsal root ganglion (DRG), and the whole cell patch clamp was used to examine the amplitude of P2X currents in the DRG neurons. The basal muscle temperature (Tm) was lower in PAD rats than in control rats. Tm was increased by ∼1.5°C and this increase was maintained for 30 min. This HT protocol was performed tweice daily for three continuous days. A greater blood pressure (BP) response to contraction was observed in PAD rats. HT attenuated the amplification of the BP response in PAD rats. HT also attenuated the enhancement of the BP response induced by the arterial injection of αβ‐me ATP in PAD rats. In addition, HT attenuated the upregulation of the P2X3 and increased P2X currents in the DRG neurons of PAD rats. In conclusion, previous heat exposure plays an inhibitory role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction of the activity of the P2X receptor pathway is probably a part of mechanisms leading to the beneficial effects of HT. Key points: During exercise, the blood pressure (BP) response is exaggerated in peripheral artery disease (PAD).We examined whether heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in PAD rats.With HT (increase in basal muscle temperature of ∼1.5°C for 30 min, twice daily for three continuous days), the amplified BP response to muscle contraction is alleviated in PAD.We demonstrated that HT attenuates the enhancement of the BP response induced by stimulation of P2X in muscle afferent nerves of PAD rats. HT also attenuates the upregulation of the P2X3 and the increase in P2X currents in the muscle afferent neurons of PAD rats.Previous heat exposure plays a beneficial role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction in the activity of the P2X receptor pathway is probably a part of the mechanism mediating this improvement. [ABSTRACT FROM AUTHOR]

Background: Emerging studies have found inconsistent results on the potential relationship between cigarette smoking and dysmenorrhea. Therefore, the aim of this study was to quantitatively synthesize the previous findings on the preceding relationship using meta-analysis. Methods: Previous studies on the association between cigarette smoking and dysmenorrhea, published not later than November 2019, were systematically searched, using MeSH heading and/or relevant terms, in the electronic databases of PubMed, Medline, Web of Science and EMBASE. The I2 statistic was used to assess heterogeneity, whose source was explored using subgroup analysis. A pooled effect size was obtained using random effects model, and sensitivity analysis was performed to assess the consistency of the pooled effect size. Results: After a rigorous screening process, 24 studies involving 27,091 participants were included in this meta-analysis. The results indicated that smokers were 1.45 times more likely to develop dysmenorrhea than non-smokers (odds ratio (OR) = 1.45, 95% confidence interval (CI): 1.30–1.61). In addition, individuals classified as currently smoking were 1.50 times more likely to develop dysmenorrhea than those who were classified as never smoking (OR = 1.50, 95% CI: 1.33–1.70), whereas being a former smoker was 1.31 times more likely to develop dysmenorrhea than being a never smoker (OR = 1.31, 95% CI: 1.18–1.46). Sensitivity analysis showed that exclusion of any single study did not materially alter the overall combined effect. Conclusion: The evidence from this meta-analysis indicated a significant association between cigarette smoking (both current and former smoking) and dysmenorrhea. The adverse effects of smoking provide further support for prevention of dysmenorrhea and emphasize the need to target women. [ABSTRACT FROM AUTHOR]

Background. Emerging studies have explored the association between the famine exposure during early life and the risk of the metabolic syndrome, and the results remain controversial. This meta-analysis was performed to summarize the famine effects on the prevalence of metabolic syndrome (MetS) in adulthood. Materials and Methods. We searched the PubMed, Web of Science, Embase, ScienceDirect, and Chinese National Knowledge Infrastructure for relevant studies up to December 2019. Pooled odd ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the effect exposure to famine on MetS using a random-effects model, and the I 2 was used to evaluate the heterogeneity. Results. The analyses included 39 studies from 10 articles with a total of 81504 participants. Fourteen studies from 10 articles for fetal famine exposure, 20 studies from 7 articles for childhood famine exposure, and 5 studies from 3 articles for adolescence/adult famine exposure were included in this meta-analysis. Compared with a nonexposed group, famine exposure significantly increased the risk of MetS for early life famine exposure (OR = 1.27 , 95% CI: 1.18-1.38), fetal famine exposure (OR = 1.27 , 95% CI: 1.14-1.43), and childhood famine exposure (OR = 1.29 , 95% CI: 1.16-1.44). Subgroup analyses showed that the result was consistent regardless of the study designs, definitions of MetS, and causes of famine, with or without adjustment for age, smoking, drinking, and physical activity. Conclusions. This meta-analysis suggests that exposure to famine during early life may increase the risk of MetS in adulthood. [ABSTRACT FROM AUTHOR]

To study the effect of dietary supplementation of Bacillus licheniformis FA6 on the growth, survival and intestinal health of grass carp, we assessed the antioxidant capacity, intestinal barrier, expression levels of immune genes, and the resistance to Aeromonas hydrophila AH-1 infection. Experimental setup comprised three groups (90 specimens each; average initial weight = 16.5 g): the control group was fed the basal diet without B. licheniformis , the low-dose (LD) group was supplemented with B. licheniformis at the concentration of 1 × 105 cfu/g, and the high-dose (HD) group with 1 × 106 cfu/g. After 56 days of growth trial, the challenge test with A. hydrophila AH-1 was conducted for 14 days. The results revealed that the grass carp in LD group and HD group had significantly (p < 0.05) improved percent weight gain (PWG) and specific growth rate (SGR) parameters. Additionally, the antioxidant status was improved, which included increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) levels in the serum, and upregulated mRNA levels of antioxidant enzymes MnSOD and catalase (CAT) in the intestine. Meanwhile, B. licheniformis FA6 supplementation groups exhibited a decreased mRNA expression of proinflammatory cytokines (such as IL-1β and TNF-α) and increased the expression of anti-inflammatory cytokine IL-10. Histological (villi length was increased) and gene expression (qPCR: upregulated ZO-1 , occludin , and claudin-c) analyses suggested improved functioning of the intestinal barrier. Post-challenge mortality rates in LD and HD groups were significantly lower (56.6% and 70% respectively) than in the control group (100%). Overall, these results indicated that dietary supplementation of B. licheniformis FA6 can improve growth, antioxidant capacity, intestinal barrier functions and disease resistance of grass carp. • Supplementing Bacillus licheniformis FA6 enhanced growth performance of grass carp. • ...increased the antioxidant capacity of grass carp. • ...strengthened the tight junctions and down-regulated pro-inflammatory cytokines in the intestine. • ...and enhanced its resistance against Aeromonas hydrophila. [ABSTRACT FROM AUTHOR]

The Human Genome Project revealed that >90% of the human genome was found to transcribe non-coding RNAs, including micro RNAs and long non-coding RNAs (lncRNAs). lncRNAs have been identified to play a crucial role in cancer progression. Thyroid cancer (TC) is a common type of endocrine cancer; however, the functional roles of lncRNAs in TC have yet to be fully elucidated. The present study investigated whether LINC01420 was upregulated in TC tissues, compared with normal thyroid tissues, and the results suggested that LINC01420 may play a regulatory role in TC. Bioinformatics analysis demonstrated that LINC01420 was associated with translation, rRNA processing, mRNA splicing, regulation of transcription, DNA repair and double-strand break repair. Furthermore, the exact role of LINC01420 in TC was explored by performing a loss-of-function assay, which revealed that the knockdown of LINC01420 inhibited TC cell proliferation and cell cycle progression. The findings of the present study provide a novel insight into the molecular mechanisms underlying TC development. Moreover, they suggest that LINC01420 may serve as a potential therapeutic target for the treatment of TC, and that increased LINC01420 expression levels show potential as a prognostic marker for the disease. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fourth largest cancer in the world, with a 5‐year survival rate of <30%. Thus, this study intends to investigate the effects of inhibin βA (INHBA) gene silencing on the migration and invasion of GC cells via the transforming growth factor‐β (TGF‐β) signaling pathway. Initially, this study determined the expression of INHBA and the TGF‐β signaling pathway‐related genes in GC tissues. After that, to assess the effect of INHBA silencing on GC progression, GC cells were transfected with short hairpin RNAs that targeted INHBA in order to detect the expression of INHBA and the TGF‐β signaling pathway‐related genes, as well as cell migration, invasion, and proliferation abilities. Finally, a tumor xenograft model in nude mice was constructed to verify the effect that the silencing of INHBA had on tumor growth. Highly expressed INHBA and activated TGF‐β signaling pathways were observed in GC tissues. In response to shINHBA‐1 and shINHBA‐2, the TGF‐β signaling pathway was inhibited in GC cells, whereas the GC cell migration, invasion, proliferation, and tumor growth were significantly dampened. On the basis of the observations and findings of this study, INHBA gene silencing inhibited the progression of GC by inactivating the TGF‐β signaling pathway, which provides a potential target in the treatment of GC. [ABSTRACT FROM AUTHOR]

In this paper we report a series of Al(III) complexes supported by N,O-bidentate β-pyrazyl functionalized enolate ligands HL1–HL5 (L = (6-Me-2,5-C4H2N2)–CH＝C(R)–O–), (R = tBu, Ph, p-tolyl, p-OMePh, o-tolyl) and their exploitation for the ring-opening polymerization of ε-caprolactone (ε-CL) and rac-lactide (rac-LA). The structures of the form LAlMe2 (1a–5a) or L2AlMe (1b–4b) were isolated depending on the ligand or stoichiometry of complexation. The investigation of these complexes toward the ROP of both ε-CL and rac-LA under the same conditions showed that dimethyl-aluminum complexes LAlMe2 (1a–5a) gave a higher activity than monomethyl-aluminum complexes L2AlMe (1b–4b). Meanwhile, monomethyl-aluminum complexes 1b–4b promoted the ring-opening polymerization with a better control over molecular weights and polydispersities than 1a–5a. Moreover, all of the LAlMe2 and L2AlMe produced PLA with strong isotactic bias (Pm up to 0.77) and narrow distributions. Generally, a β-pyrazyl enolate system exhibited significantly higher catalytic activity for the ROP of ε-CL and rac-LA than the analogous β-quinolyl enolate systems reported recently. The results are discussed in terms of electronic and steric properties affected by the substituents on the ligands. [ABSTRACT FROM AUTHOR]

By employment of an aptamer-initiated hybridization chain reaction (HCR) to enhance the enzyme biomineralization of cupric subcarbonate, this work develops a novel colorimetric biosensing method for protein analysis. The HCR product was used to specifically attach a large amount of urease-functionalized gold nanoparticles (Au NPs) for the preparation of a gold nanoprobe. After the sandwich biorecognition reactions, this nanoprobe could be quantitatively captured onto the antibody-functionalized magnetic bead (MB) platform. Then, numerous copper ions would be enriched onto the MB surface through the urease-induced biomineralization of cupric subcarbonate. Based on the complete release of Cu2+ ions for the sensitive copper chromogenic reaction, convenient colorimetric signal transduction was thus achieved for the quantitative analysis of the target analyte of the carcinoembryonic antigen. The HCR product provides a large number of biotin sites for the attachment of Au NP nanotags. The biomineralization reaction of high-content urease loaded onto Au NPs leads to highly efficient Cu2+ enrichment for signal amplification. So this method features excellent performance including a very wide linear range and a low detection limit down to 0.071 pg mL−1. In addition, the satisfactory results of real sample experiments reveal that this method possesses huge potential for practical applications. [ABSTRACT FROM AUTHOR]

Summary: Symbiotic nitrogen (N2) fixation plays a vital role in sustainable agriculture. Efficient N2 fixation requires various materials, including phosphate (Pi); however, the molecular mechanism underlying the transport of Pi into nodules and bacteroids remains largely unknown.A nodule‐localized Pi transporter, GmPT7, was functionally characterized in soybean (Glycine max) and its role in N2 fixation and yield was investigated via composite and whole transgenic plants.GmPT7 protein was localized to the plasma membrane and showed transport activity for Pi in yeast. Altered expression of GmPT7 changed 33Pi uptake from rhizosphere and translocation to bacteroids. GmPT7 was mainly localized to the outer cortex and fixation zones of the nodules. Overexpression of GmPT7 promoted nodulation, and increased plant biomass, shoot nitrogen and phosphorus content, resulting in improved soybean yield by up to 36%. Double suppression of GmPT5 and GmPT7 led to nearly complete elimination of nodulation and over 50% reduction in plant biomass, shoot nitrogen and phosphorus content, indicating that both GmPT7 and GmPT5 contribute to Pi transport for N2 fixation.Taken together, our results indicate that GmPT7 is a transporter responsible for direct Pi entry to nodules and further to fixation zones, which is required for enhancing symbiotic N2 fixation and grain yield of soybean. [ABSTRACT FROM AUTHOR]

Abstract Orthogonal turn-milling is a primary method of turn-milling, which is used for cutting. It is widely used for machining difficult-to-cut materials, slender rods, thin-wall rotary parts, and large rotary parts. As with turning and milling, chatter is generated by orthogonal turn-milling and affects machining productivity, machining accuracy, and tool life. Various methods are available to predict the chatter-stability lobes of orthogonal turn-milling, such as the zero-order analytical, multi-frequency solution, temporal finite-element-analysis, semi-discretization, and full-discretization methods. However, the zero-order analytical method may not be suitable for the actual conditions of orthogonal turn-milling. The multi-frequency solution, temporal finite-element analysis, and semi-discretization methods suffer from poor efficiency, and the full-discretization method involves complex iterative equations and halfway discretization. To overcome these obstacles, we propose herein a different stability model for orthogonal turn-milling. We use this model to investigate a cutting process for orthogonal turn-milling and obtain stability-lobe diagrams using the complete discretization method based on the Eulerian method. The diagrams are verified by comparing them against the experimental results for chatter. Furthermore, we simulate and analyze how feed per revolution of tools affects the cutting stability for orthogonal turn-milling. These models and results can provide theoretical guidance for maximizing the processing efficiency and surface quality of workpiece manufactured by orthogonal turn-milling. Highlights • The dynamical models of cutting process are a foundation for stability modeling of orthogonal turn-milling. • The complete discretization method can be applied to orthogonal turn-milling and correctly forecasted the stability. • f a is a principal cutting parameter of orthogonal turn-milling and strongly influences the chatter stability. • The chatter is less likely to happen during finishing machining for orthogonal turn-milling of TC21. [ABSTRACT FROM AUTHOR]

Supergraph search is a fundamental problem in graph databases that is widely applied in many application scenarios. Given a graph database and a query-graph, supergraph search retrieves all data-graphs contained in the query-graph from the graph database. Most existing solutions for supergraph search follow the pruning-and-verification framework, which prune false answers based on features in the pruning phase and perform subgraph isomorphism testings on the remaining graphs in the verification phase. However, they are not scalable to handle large-sized data-graphs and query-graphs due to three drawbacks. First, they rely on a frequent subgraph mining algorithm to select features which is expensive and cannot generate large features. Second, they require a costly verification phase. Third, they process features in a fixed order without considering their relationships to the query-graph. In this paper, we address the three drawbacks and propose new indexing and query processing algorithms. In indexing, we select features directly from the data-graphs without expensive frequent subgraph mining. The features form a feature-tree that contains all-sized features and both the cost sharing and pruning power of the features are considered. In query processing, we propose a new algorithm, where the order to process features is query-dependent by considering both the cost sharing and the pruning power. We explore two optimization strategies to further improve the algorithm efficiency. The first strategy applies a lightweight graph compression technique and the second strategy optimizes the inclusion of answers. We further introduce how to efficiently maintain the index incrementally when the graph database is updated dynamically. Moreover, we propose an approximation approach to significantly reduce the computational cost for large data-graphs and/or query-graphs while preserving a high result quality. Finally, we conduct extensive performance studies on two real large datasets to demonstrate the efficiency and effectiveness of our algorithms. [ABSTRACT FROM AUTHOR]

Core decomposition is a fundamental graph problem with a large number of applications. Most existing approaches for core decomposition assume that the graph is kept in memory of a machine. Nevertheless, many real-world graphs are too big to reside in memory. In this paper, we study I/O efficient core decomposition following a semi-external model, which only allows node information to be loaded in memory. We propose a semi-external algorithm and an optimized algorithm for I/O efficient core decomposition. To handle dynamic graph updates, we firstly show that our algorithm can be naturally extended to handle edge deletion. Then, we propose an I/O efficient core maintenance algorithm to handle edge insertion, and an improved algorithm to further reduce I/O and CPU cost. In addition, based on our core decomposition algorithms, we further propose an I/O efficient semi-external algorithm for degeneracy ordering, which is an important graph problem that is highly related to core decomposition. We also consider how to maintain the degeneracy order. We conduct extensive experiments on 12 real large graphs. Our optimal core decomposition algorithm significantly outperforms the existing I/O efficient algorithm in terms of both processing time and memory consumption. They are very scalable to handle web-scale graphs. As an example, we are the first to handle a web graph with 978.5 million nodes and 42.6 billion edges using less than 4.2 GB memory. We also show that our proposed algorithms for degeneracy order computation and maintenance can handle big graphs efficiently with small memory overhead. [ABSTRACT FROM AUTHOR]

The synthesis of mono-nuclear β-pyridylenolate zinc complexes L 1 2 Zn ( 1 ) (L 1 = (2-C 5 H 4 N)–CH=C(CH 3 )–O–) and L 2 2 Zn ( 2 ) (L 2 = (2-C 5 H 4 N)–CH=C (2-CH 3 C 6 H 5 )–O–) were performed by the protonolysis of the corresponding β-pyridylenol bidentate ligands 1-(2-pyridinyl)-2-propanone (L 1 H) and 1-(2-methylphenyl)-2-(2-pyridinyl)-ethanone (L 2 H) with diethylzinc in a 2:1 M ratio, respectively. The unanticipated tetra-nuclear β-pyridylenolate zinc complex [L 1 2 Zn- μ -O (Et)ZnEt] 2 ( 3 ) was isolated by the reaction of L 1 H with an equiv. of ZnEt 2 and oxygenation with air. All the complexes were well characterized by single crystal X-ray crystallography. Complexes 1 – 3 were tested as an initiator for the ring opening polymerization (ROP) of ε-caprolactone and l -lactide. In the same conditions, 1 and 2 are shown inefficient for ROP due to the lack of suitable initiating group for polymerization, however, tetra-nuclear complex 3 is a highly active single-component initiator in the ROP of ε-caprolactone and l -lactide. Complex 3 was also researched for its catalytic activity in block (PCL- b -PLLA) and gradient (LA- grad -CL) copolymerization of ε-caprolactone and l -lactide. [ABSTRACT FROM AUTHOR]

The peroxisome proliferator-activated receptor-α (PPAR-α) agonist fenofibrate ameliorates cardiac hypertrophy; however, its mechanism of action has not been completely determined.Our previous study indicated that a disintegrin andmetalloproteinase-17 (ADAM17) is required for angiotensin II-induced cardiac hypertrophy. This study aimed to determinewhetherADAM17 is involved in the protective action of fenofibrate against cardiac hypertrophy. Abdominal artery constriction- (AAC-) induced hypertensive rats were used to observe the effects of fenofibrate on cardiac hypertrophy and ADAM17 expression. Primary cardiomyocytes were pretreatedwith fenofibrate (10 μM) for 1 hour before being stimulatedwith angiotensin II (100 nM) for another 24 hours. Fenofibrate reduced the ratios of left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW), left ventricular anterior wall thickness (LVAW), left ventricular posterior wall thickness (LVPW), and ADAM17 mRNA and protein levels in left ventricle in AAC-induced hypertensive rats. Similarly, in vitro experiments showed that fenofibrate significantly attenuated angiotensin II-induced cardiac hypertrophy and diminished ADAM17 mRNA and protein levels in primary cardiomyocytes stimulated with angiotensin II. In summary, a reduction in ADAM17 expression is associated with the protective action of PPAR-α agonists against pressure overload-induced cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Exceptional points (EPs) in non-Hermitian systems have attracted enormous attention and spawned intriguing prospects for the manipulation of waves. Despite many efforts focusing on the exotic behaviors about EPs, there are only a few studies of phase transitions involving multiple EPs. Here, by employing staggered couplings as well as two pairs of on-site gain/loss, we propose a one-dimensional parity-time (P T)-symmetric Lieb photonic lattice and demonstrate diverse phase transitions of such a multiband structure. Owing to the non-Hermitian chiral symmetry, symmetry-protected higher-order EPs are constructed, and the system exhibits P T symmetry breaking beyond a certain threshold. More importantly, both the relative couplings and the on-site gain/loss can be flexibly reconfigured on demand, which yields the degeneracy of different bands, i.e., the emergence of multiple EPs. We also unveil that the EPs will no longer exist in the presence of a non-Hermitian diagonal disorder. In contrast, the spectrum remains symmetric and the EPs, along with the flatband, are robust against the off diagonal disorder due to the preserved non-Hermitian particle-hole symmetry. Our work not only provides a controllable platform for studying EPs but also sheds light on the exciting non-Hermitian physics based on exceptional degeneracies. [ABSTRACT FROM AUTHOR]

Community search is important in graph analysis and can be used in many real applications. In the literature, various community models have been proposed. However, most of them cannot well identify the overlaps between communities which is an essential feature of real graphs. To address this issue, the k -clique percolation community model was proposed and has been proven effective in many applications. Motivated by this, in this paper, we adopt the k -clique percolation community model and study the densest clique percolation community search problem which aims to find the k -clique percolation community with the maximum k value that contains a given set of query nodes. We adopt an index-based approach to solve this problem. Based on the observation that a k - \mathsf Index , to preserve the maximal cliques and their connectivity information of the input graph. With \mathsf DCPC- \mathsf Index , we can answer the densest clique percolation community query efficiently. Besides, we also propose an index construction algorithm based on the definition of \mathsf DCPC - \mathsf Index and further improve the algorithm in terms of efficiency and memory consumption. We conduct extensive performance studies on real graphs and the experimental results demonstrate the efficiency of our index-based query processing algorithm and index construction algorithm. [ABSTRACT FROM AUTHOR]

This work investigated the reactivity of 2-benzylpyridyl lithium (2-Pyr)C(Ph)(R)Li (R = SiMe 3 , Li1 ; R = H, Li2 ) toward benzonitrile derivatives. Based on the different products, the reaction between lithium salts and nitriles might involve in addition, elimination and bimolecular coupling pathways, respectively. Treatment of Li1 with ArCN (Ar = Ph, p -Tolyl, o -Tolyl, p -OMePh) yielded an addition intermediate pyridyl-1-aza-allyl-lithium [{(2-Pyr)C(Ph)C(Ar)N(SiMe 3 )}Li] 2 ( 1, Ar = Ph) and its corresponding hydrolysis product 2-benzylpyridyl-ketone 2 – 5 , respectively, in which the reaction involved in a 1,3-shift of -SiMe 3 group to form a dimeric pyridyl-1-aza-allyl-lithium then followed by acidic hydrolysis. The MeOLi elimination reaction between Li2 and p -MeO(C 6 H 4 )CN resulted in formation of 4-(2-benzylpyridyl)benzonitrile 6 . The reaction of Li2 with p -Me(C 6 H 4 )CN in the presence of TMEDA generated a 1:2 hydrolysis adduct 2-benzylpyridyl-enaminone 7 , however, in the absence of TMEDA it afforded a coupling product of bimolecular nitriles, 1-(4-methylphenyl)-2-cyanophenyl-ethanone 8 . We speculated the reaction mechanisms in sequence. The crystal structures of 1 and 5 – 8 were analyzed. [ABSTRACT FROM AUTHOR]