Tuneable Efficient White Emission of Sb3+/Mn2+ Co-Doped Lead-Free Perovskites for Single-Component White Light-Emitting Diodes.

Inorganic lead-free perovskite nanocrystals (NCs) with broadband self-trapped exciton (STEs) emission and low toxicity have shown enormous application prospects in the field of display and lighting. However, white light-emitting diodes (WLEDs) based on a single-component material with high photoluminescence quantum yield (PLQY) remain challenging. Here, we demonstrate a novel codoping strategy by introducing Sb3+/Mn2+ ions to achieve the tuneable dual emission in lead-free perovskite Cs3InCl6 NCs. The PLQY increases to 59.64% after doping with Sb3+. The codoped Cs3InCl6 NCs exhibit efficient white light emission due to the energy transfer channel from STEs to Mn2+ ions with PLQY of 51.38%. Density functional theory (DFT) calculations have been used to verify deeply the effects of Sb3+/Mn2+ doping. WLEDs based on Sb3+/Mn2+-codoped Cs3InCl6 NCs are explored with color rendering index of 85.5 and color coordinate of (0.398, 0.445), which have been successfully applied as photodetector lighting sources. This work provides a new perspective for designing novel lead-free perovskites to achieve single-component WLEDs.

Thermal stability and interfacial rheology of whey protein-corn oil emulsions: The effect of l-arginine fortification.

The effect of l-arginine (Arg) on the thermal stability of whey protein-corn oil emulsions was investigated to determine its role in improving emulsion stability. The results indicated that with an increase in Arg concentration, the emulsion stability index, emulsification activity index, and absolute ζ-potential increased initially and decreased after high-temperature sterilization. However, the mean particle size, apparent viscosity, creaming indices, and dynamic interfacial pressure of the emulsions first decreased and then increased, and the performance of samples that only showed an increase in pH could also improve the emulsification stability. These results clarify the mechanism by which Arg increases the thermal stability of emulsions.

A hybrid method of frequency-weighted energy operator and power spectrum fusion to detect bearing faults.

The difficulties in early fault diagnosis of bearings mainly include two aspects: first, the initial damage size of the bearing is small, and the abnormal vibration caused by slight damage to the bearing is very weak. Second, vibration signals collected in actual industrial environments always contain strong noise interference. Therefore, traditional diagnostic procedures are not satisfactory. To address these challenges, this work provides a hybrid model combining frequency-weighted energy operator (FWEO) with power spectrum fusion (PSF) to identify weak fault features of bearings and detect different fault types. Different from traditional time-domain signal filtering, PSF is first used to reduce the interference of noise components in the power spectrum, which will not weaken the fault signal components during denoising. Second, the filtered signal is transformed into the time domain and FWEO is employed to further enhance the cyclic fault signal caused by the weak defect of the bearing. Finally, the existence of a fault is identified by observing the squared envelope spectrum of the signal. The effectiveness of the proposed hybrid model is demonstrated through two simulated fault signals and three different experimental fault signals. The results show that the proposed model has high anti-noise performance and robustness and can extract the fault frequency well.

Evaluation of left ventricular myocardial work in patients with hyperthyroidism with different heart rates with noninvasive pressure-strain loop based on two-dimensional speck tracking imaging.

Background: We investigated the application value of no-invasive myocardial work in evaluating left ventricular (LV) function in patients with hyperthyroidism. Methods: Sixty-five patients with an initial hyperthyroidism diagnosis were sorted into tachycardia (group TH1, n=31) and without tachycardia (group TH2, n=34) groups. Thirty healthy participants served as the control group (group CON). LV strain parameters and LV myocardial work parameters were evaluated at rest. Each parameter's value in identifying myocardial damage was analyzed using receiver operating characteristic curves. The correlation of myocardial work parameters with global longitudinal strain (GLS), longitudinal peak strain dispersion (normalized by heart rate, PSDN), and systolic blood pressure (SBP) was analyzed. Results: There was no difference in classic echocardiographic parameters between the groups. Compared with that in group CON, GLS decreased in groups TH1 and TH2 (TH1 17.99%±2.21% and TH2: 19.00%±2.85% vs. 20.27%±1.49%; both P<0.05); there was no significant difference between groups TH1 and TH2. PSDN increased in groups TH1 and TH2 (TH1 73.13±19.51 ms and TH2 55.06±17.03 vs. 44.13±8.65 ms; both P<0.05); it was higher in group TH1 than in group TH2 (P<0.05). Myocardial global work efficiency (GWE) decreased in groups TH1 and TH2 {TH1 95% [interquartile range (IQR), 94-95%] and TH2 96% (IQR, 95-97%) vs. 97% (IQR, 96-97%); both P<0.05}; it was lower in group TH1 than in group TH2 (P<0.05). Global constructive work (GCW) decreased in group TH1 (1,865.29±284.13 vs. 2,030.33±252.52 mmHg%; P<0.05), but was not different from that in group TH2; there was no difference between groups TH2 and CON. Global wasted work (GWW) increased in groups TH1 and TH2 [TH1 83.00 (IQR, 74.00-97.00) mmHg% and TH2 69.50 (IQR, 51.25-84.25) vs. 50.50 (IQR, 40.75-65.25) mmHg%; both P<0.05]; it was higher in group TH1 than in group TH2 (P<0.05). The area under the GWE curve was the largest (area under the curve =0.835), and the optimal cutoff point was 96.5%, with a sensitivity of 0.83 and a specificity of 0.70. GWE and GCW were positively correlated with GLS and negatively correlated with PSDN. GWW was negatively correlated with GLS and positively correlated with PSDN. In group CON, GCW and GWW were positively correlated with SBP; GWE was not correlated with SBP. In groups TH1 and TH2, GCW was positively correlated with SBP, but not with GWW or GWE. Conclusions: Hyperthyroidism can significantly decrease the GWE and increase GWW of the left ventricle. This change is more pronounced in patients with tachycardia. Myocardial work could be a novel method for the evaluation of LV myocardial function in patients with hyperthyroidism.

Prediction of Surgical Approach in Mitral Valve Disease by XGBoost Algorithm Based on Echocardiographic Features.

In this study, we aimed to develop a prediction model to assist surgeons in choosing an appropriate surgical approach for mitral valve disease patients. We retrospectively analyzed a total of 143 patients who underwent surgery for mitral valve disease. The XGBoost algorithm was used to establish a predictive model to decide a surgical approach (mitral valve repair or replacement) based on the echocardiographic features of the mitral valve apparatus, such as leaflets, the annulus, and sub-valvular structures. The results showed that the accuracy of the predictive model was 81.09% in predicting the appropriate surgical approach based on the patient's preoperative echocardiography. The result of the predictive model was superior to the traditional complexity score (81.09% vs. 75%). Additionally, the predictive model showed that the three main factors affecting the choice of surgical approach were leaflet restriction, calcification of the leaflet, and perforation or cleft of the leaflet. We developed a novel predictive model using the XGBoost algorithm based on echocardiographic features to assist surgeons in choosing an appropriate surgical approach for patients with mitral valve disease.

Left atrial reservoir and pump function after catheter ablation with persistent atrial fibrillation: a two-dimensional speckle tracking imaging study.

OBJECTIVE: By using ultrasound strain rate (SR) imaging to evaluate the left atrial (LA) reservoir and pump function after catheter ablation (CA) with persistent atrial fibrillation (PAF). METHODS: A total of 45 patients with PAF underwent echocardiography examination before and after ablation as well as during 6 months of follow-up. Peak SR was measured at each LA segment (septal, lateral, anterior, inferior and posterior) during systole (LAs) and late diastole (LAa). RESULTS: During 6 months after CA, 30 patients were free of atrial fibrillation recurrence (AFR). left atrial area index (LAAI), left atrial maximum volume index (LAVImax), and E/Ea were obviously higher in patients with before CA, left atrial ejection fraction (LAEF), SR-LAs were lower than in normal cases, the SR-LAa was disappeared. Shortly after ablation, SR-LAa was recovered, and SR-LAs was reduced compared to those at baseline. At midterm follow-up, LAEF and SR-LAs were still lower than the control group, and LAAI and LAVImax were higher. SR-LAa was recovered slowly over time, but still lower. CONCLUSION: LA reservoir function was seriously damaged and LA pump function disappeared in patients with PAF. LA reservoir function impairment appeared shortly after ablation, it showed improvement at midterm follow-up, but some degree of damage to the LA reservoir and pump function was still present. Speckle tracking imaging is a feasible technique for the assessment of LA function in patients with PAF, which is a potentially valuable clinical tool to assist in the early detection of atrial remodelling and reverse remodelling.

Construction and validation of a progression prediction model for locally advanced rectal cancer patients received neoadjuvant chemoradiotherapy followed by total mesorectal excision based on machine learning.

Background: We attempted to develop a progression prediction model for local advanced rectal cancer(LARC) patients who received preoperative neoadjuvant chemoradiotherapy(NCRT) and operative treatment to identify high-risk patients in advance. Methods: Data from 272 LARC patients who received NCRT and total mesorectal excision(TME) from 2011 to 2018 at the Fourth Hospital of Hebei Medical University were collected. Data from 161 patients with rectal cancer (each sample with one target variable (progression) and 145 characteristic variables) were included. One Hot Encoding was applied to numerically represent some characteristics. The K-Nearest Neighbor (KNN) filling method was used to determine the missing values, and SmoteTomek comprehensive sampling was used to solve the data imbalance. Eventually, data from 135 patients with 45 characteristic clinical variables were obtained. Random forest, decision tree, support vector machine (SVM), and XGBoost were used to predict whether patients with rectal cancer will exhibit progression. LASSO regression was used to further filter the variables and narrow down the list of variables using a Venn diagram. Eventually, the prediction model was constructed by multivariate logistic regression, and the performance of the model was confirmed in the validation set. Results: Eventually, data from 135 patients including 45 clinical characteristic variables were included in the study. Data were randomly divided in an 8:2 ratio into a data set and a validation set, respectively. Area Under Curve (AUC) values of 0.72 for the decision tree, 0.97 for the random forest, 0.89 for SVM, and 0.94 for XGBoost were obtained from the data set. Similar results were obtained from the validation set. Twenty-three variables were obtained from LASSO regression, and eight variables were obtained by considering the intersection of the variables obtained using the previous four machine learning methods. Furthermore, a multivariate logistic regression model was constructed using the data set; the ROC indicated its good performance. The ROC curve also verified the good predictive performance in the validation set. Conclusions: We constructed a logistic regression model with good predictive performance, which allowed us to accurately predict whether patients who received NCRT and TME will exhibit disease progression.

Enriched-Bromine Surface State for Stable Sky-Blue Spectrum Perovskite QLEDs With an EQE of 14.6.

Halogen vacancies are of great concern in blue-emitting perovskite quantum-dot light-emitting diodes because they affect their efficiency and spectral shift. Here, an enriched-bromine surface state is realized using a facile strategy that employs a PbBr2 stock solution for anion exchange based on Cd-doped perovskite quantum dots. It is found that the doped Cd ions are expected to reduce the formation energy of halogen vacancies filled by the external bromine ions, and the excess free bromine ions in solution are enriched in the surface by anchoring with halogen vacancies as sites, accompanied with the shedding of surface long-chain ligands during the anion exchange process, resulting in a Br-rich and "neat" surface. Moreover, the surface state exhibits good passivation of the surface defects of the controlled perovskite QDs and simultaneously increases the exciton binding energy, leading to excellent optical properties and stability. Finally, the sky-blue emitting perovskite quantum-dot light-emitting diodes (QLEDs) (490 nm) are conducted with a record external quantum efficiency of 14.6% and current efficiency of 19.9 cd A-1 . Meanwhile, the electroluminescence spectra exhibit great stability with negligible shifts under a constant operating voltage from 3 to 7 V. This strategy paves the way for improving the efficiency and stability of perovskite QLEDs.

Early assessment of subclinical myocardial injury in systemic lupus erythematosus by two-dimensional longitudinal layer speckle tracking imaging.

Background: To investigate the feasibility of quantitatively assessing left ventricular function and synchronization and diagnose subclinical myocardial injury in patients with systemic lupus erythematosus (SLE) using two-dimensional (2D) longitudinal layer speckle tracking imaging (STI). Methods: This was a single-center prospective study. A total of 69 patients with SLE were included in the case group and further divided into 2 subgroups, a nonactive and an active group, according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 scoring standard. We selected 30 healthy volunteers as the control group. The global longitudinal strain (GLSglobal), global endocardial longitudinal strain (GLSendo), global epicardial longitudinal strain (GLSepi), and peak strain dispersion (PSD) were obtained. The transmural gradient of longitudinal strain (TGLS) was calculated for the difference in strains between the inner and outer membranes. Results: (I) Compared with the control group, decreased speckle strain parameters and elevated PSD were observed in patients with SLE (GLSglobal: -18.80%±2.41% vs. -21.19%±2.16%, GLSendo: -21.15%±2.47% vs. -24.09±2.49%; GLSepi: -16.58%±2.39% vs. -18.50±1.77%; TGLS: -4.56%±1.24% vs. -5.59%±1.39%; and PSD: 36.61±10.85 vs. 30.00±8.54 ms). More severely impaired layer strains were observed in active-stage patients. Compared with the nonactive group, GLSendo, GLSglobal, GLSepi, TGLS, complement C3, and complement C4 were decreased in the active group, while SLEDAI, erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (Hs-CRP) were elevated. (II) Receiver operating characteristic (ROC) analysis demonstrated that subendocardial myocardial longitudinal strain was the most powerful tool for detecting myocardial insufficiency early in patients with SLE [area under the curve (AUC) =0.809], especially in patients in the active stage (AUC =0.734), and the optimal cut-off point was -21.35%, with a sensitivity of 71.9% and a specificity of 62.2%. (III) Correlation analysis revealed that GLSendo was moderately correlated with PSD, SLEDAI, ERS, Hs-CRP, and complement C3 (correlation coefficients: 0.535, 0.428, 0.659, 0.559, and -0.440, respectively). Conclusions: Subclinical myocardial injury in patients with SLE can be assessed early using 2D longitudinal STI, and the injury is more obvious in active-stage patients. Endocardial longitudinal strain is a more sensitive index than epicardial longitudinal strain for the early detection of subclinical myocardial injury in patients with SLE, which is a potentially valuable clinical tool to assist in the early detection of myocardial damage.

Noninvasive Evaluation of Myocardial Work in Patients with Chronic Kidney Disease Using Left Ventricular Pressure-Strain Loop Analysis.

(1) Objective: To evaluate myocardial injury by observing the different parameters of global myocardial work (MW) by left ventricular pressure-strain loop (PSL) analysis in patients with chronic kidney disease (CKD). (2) Methods: According to the left ventricular mass index, the study patients with CKD were further divided into two groups: the left ventricular normal group (CKDN-LVH, 59) and left ventricular hypertrophy group (CKDLVH, 46). Thirty-three healthy controls (CON) matched in age and sex with the CKD group were recruited. The routine ultrasonic parameters were obtained by routine TTE, and the strain index and different parameters of the left ventricular MW were obtained by dynamic image offline analysis. (3) Results: This study found that (1) compared with the CON group, the CKDN-LVH group had a significantly increased global waste work (GWW) and significantly decreased global work efficiency (GWE), the GWW further increased, and GWE further decreased in the CKDLVH group. There was no significant change in the global work index (GWI) and global constructive work index (GCW) in the CKDN-LVH group, but the GWI and GCW in the CKDLVH group were significantly increased. (2) According to the grouping analysis of systolic blood pressure (SBP), we found that the GWW increased and GWE decreased in CKD patients with an elevated SBP. (3) Correlation analysis showed that the increase of the peak strain dispersion, SBP, and left ventricular mass index and the decrease of the estimated glomerular filtration rate were significantly correlated with the decrease of the GWE and the increase of the GWW. (4) Receiver operating characteristic curve analysis showed that the area under the curve (AUC) of myocardial damage induced by the GWE and GWW in the CKD group and CON group was higher than that of left ventricular global longitudinal strain (AUCs: 0.87 and 0.878 versus 0.72, respectively). (4) Conclusions: Noninvasive left ventricular PSL analysis can be used to evaluate the global MW in patients with CKD. The study justified the role of GWW in the noninvasive assessment of myocardial function in patients with CKD.

Aortic Root Downward Movement as a Novel Method for Identification of an Adequately Performed Valsalva Maneuver to Detect Patent Foramen Ovale during Transesophageal Echocardiograph.

The Valsalva maneuver (VM) is the most sensitive auxiliary method for the detection of patent foramen ovale (PFO), but it is difficult to assess whether the maneuver is adequately performed during transesophageal echocardiography (TEE). In this study, we tried to use aortic root downward movement as a novel method for judging whether VM was adequate or not, and to evaluate whether this novel method can increase the sensitivity of detecting PFO. A total of 224 patients with clinically suspected PFO were enrolled in this study. These patients were injected with activated normal saline to detect the right-to-left shunt (RLS), in the following three conditions: contrast-enhanced transthoracic echocardiography under adequate VM (AVM cTTE), contrast-enhanced TEE under non-adequate VM (non-AVM cTEE), and cTEE under adequate VM (AVM cTEE). A novel method in which the aorta root moves downward (movement range ≥16 mm) in the cTEE judged whether AVM was performed. The PFO detection rate and sensitivity of AVM cTEE were better than that of non-AVM cTEE (detection rate: 108 PFOs [48.2%] vs. 86 PFOs [38.4%], p = 0.036; sensitivity: 100% vs. 79.6%). Among AVM cTTE, non-AVM cTEE, and AVM cTEE, the RLS grade evaluation results were inconsistent, with significant differences (p < 0.05). Non-AVM cTEE had RLS underestimation or false negatives. Compared with non-AVM cTEE, AVM cTEE and AVM cTTE had better consistency in evaluating PFO RLS (kappa value = 0.675). Aortic root downward movement could be used as a novel method for judging the effectiveness of VM, which is critical for the detection of PFO in cTEE. Concerning effectiveness and convenience, this method should be promoted during the clinical detection of PFO.

Mechanism of Lycopodii herba for RA-ILD using integrated metabolomics and network pharmacology.

Interstitial lung disease (ILD) is the most common complication of rheumatoid arthritis (RA), which highly increases the morbidity and mortality of RA. Lycopodii herba (SJC) has been used as a widespread traditional Chinese medicine to treat RA and the related complications for more than 500 years. However, its therapeutic effect on RA-ILD and related mechanisms are not clear. The purpose of this work was to confirm the efficacy of SJC for RA-ILD and clarify its mechanism. In this study, we first determined the efficacy of SJC on RA-ILD. Then, 15 potential biomarkers of SJC were identified by metabolomics in rat serum, which were mainly associated with ether lipid metabolism and arachidonic acid metabolism. 21 pathways were related to SJC by network pharmacology. Combined with the results of metabolomics and network pharmacology and real-time PCR (RT-PCR) validation, the mechanism of SJC for RA-ILD may be related to the Ras signaling pathway and PI3K-Akt signaling pathway by regulating the expression of PLA2G1B and PI3KCA. This work preliminary confirmed the preventive and therapeutic effects of SJC on RA-ILD and elucidated the mechanism from the metabolic perspective.

Left ventricular and atrial remodelling in hypertensive patients using thresholds from international guidelines and EMINCA data.

AIMS: To investigate differences in the prevalence of left ventricular (LV) and left atrial (LA) remodelling in hypertensive patients using various thresholds defined by international guidelines and data from the Echocardiographic Measurements in Normal Chinese Adults (EMINCA) study and different indexation methods. METHODS AND RESULTS: LV mass (LVM), relative ventricular wall thickness, and LA volume (LAV) were measured using 2D echocardiography in 612 healthy volunteers selected from the EMINCA study population and 306 adult Chinese patients with hypertension who were age- and gender-matched using propensity score-matched analysis. LVM and LAV values were indexed to body surface area (BSA), height2.7, height1.7, and height2 recommended by guidelines or investigators. Using a previously reported method, LV geometry was divided into normal geometry, concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. The prevalence of LV hypertrophy (LVH) and LV geometric patterns in hypertensive patients were compared using different thresholds and indexation methods. Echocardiographic thresholds from guidelines and healthy volunteers exhibited notable differences, particularly for LAV indexed to height2 and for LVM indexed to height1.7, which resulted in a significantly lower prevalence of LA dilatation and LVH in healthy volunteers. The total proportion of abnormal LV geometric patterns was significantly lower with thresholds from healthy volunteers than from guidelines when LVM was indexed to BSA, height1.7, and height2,7. CONCLUSION: Using current echocardiographic thresholds and indexing methods recommended by guidelines may lead to significant misdiagnosis of LA dilatation, and abnormal LV geometry in Chinese patients with hypertension, and thresholds based on ethnic-specific normal echocardiographic reference values and an accurate indexing algorithm are warranted.

Ethanol organosolv lignin from different agricultural residues: Toward basic structural units and antioxidant activity.

The growing interest in the substitution of synthetic food antioxidants by natural ones has fostered research on vegetable sources and the screening of raw materials for identifying new antioxidants. Special attention is focused on their extraction from inexpensive or residual sources from agricultural industries. Herein, the antioxidant activities of lignin obtained from 4 residual sources were investigated. The obtained lignin samples were characterized by different analytical techniques evaluating their chemical structure, phenolic content, thermal behavior and molecular weight. The antioxidant activity of the analyzed lignins was evaluated by the DPPH assay, the radical ABTS assay, and trivalent iron reduction method. It was found t that lignin antioxidants could scavenge free radicals and reduce oxidants. The high correlation between antioxidant capacity and its total phenol content indicated that phenolic hydroxyl groups were the main contributors to these lignins' antioxidant activity.

Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3.

Intercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

Phototropin2-mediated hypocotyl phototropism is negatively regulated by JAC1 and RPT2 in Arabidopsis.

Hypocotyl phototropism is redundantly mediated by phot1 and phot2, two blue light receptor phototropins, under the intensity of blue light>1 µmol m-2 s-1. As light intensity increases, phot1 inhibits the phot2-mediated response. To date, only Arabidopsis Root Phototropism2 (RPT2) has been shown to participate in phot1-mediated inhibition of phototropism. To dissect the signaling network that underlies phot1-mediated inhibition, we carried out a yeast two-hybrid (Y2H) screening assay for RPT2 interacting proteins and identified J-domain protein required for chloroplast accumulation response 1 (JAC1). The interaction between JAC1 and RPT2 was verified by bimolecular fluorescence complementation and Co-IP assays. JAC1 is expressed mainly in cotyledons and hypocotyls. Like RPT2, JAC1 can be induced by blue light, suggesting that it may function similarly to RPT2 in the inhibition of phototropism. Genetic analysis showed that jac1 mutation significantly enhanced the hypocotyl bending of phot1 mutants towards intermediate-intensity blue light, and this effect was inhibited by the constitutive expression of JAC1 in the phot1 jac1 mutant. The phot1 rpt2 double mutant also exhibited enhanced phototropism compared with the phot1 mutant. Taken together, our data clearly demonstrate that JAC1 cooperates with RPT2 to negatively regulate hypocotyl phototropism in plants and may act either downstream of or in parallel with phot1.

Screen the Effective Components of Lycopodii herba on Rheumatoid Arthritis with the Aid of Spectrum-Effect Relationship and Uncover its Potential Mechanism.

Lycopodii herba (SJC), a traditional Chinese medicine, has the effect of dispelling wind and eliminating dampness (a therapeutic principle and method of traditional Chinese medicine for rheumatoid arthritis), relaxing tendon and activating collaterals. However, the major effective components and its therapeutic mechanism were unclear. In this study, different SJC samples with slightly different compositions were prepared by extracting with different concentrations of ethanol. Then, the therapeutic effects on rheumatoid arthritis (RA) of different SJC samples were evaluated. Finally, the spectrum-effect relationship between UPLC-Q-TOF/MS fingerprints and the effect of RA was explored to screen the effective components. Western blotting was used to study the potential mechanism. The volume of hind paw and the level of RF, TNF-α, and IL-1ß were lower after administrating with different SJC samples, compared with the model group. Histopathological findings also confirmed that SJC could relieve the symptoms of RA. Combined with identification of the components in plasm from SJC, lycojaponicumin C, des-N-methyl-α-obscurine, 8ß-acetoxy-12ß-hydroxy-lycopodine or 8ß-acetoxy-11α-hydroxy-lycopodine or 8ß-hydroxy-11α-acetoxylycopodine were considered to be the major effective components. The mechanism may be related to AChE/NF-κB signaling pathway. This work provides a general method to screen the potential effective components of herb medicines and would be benefit to understand the mechanism of SJC for the treatment of RA.

Bidirectional Brain-gut-microbiota Axis in increased intestinal permeability induced by central nervous system injury.

Central nervous system injuries may lead to the disorders of the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and enteric nervous system. These effects then cause the changes in the intestinal microenvironment, such as a disordered intestinal immune system as well as alterations of intestinal bacteria. Ultimately, this leads to an increase in intestinal permeability. Inflammatory factors produced by the interactions between intestinal neurons and immune cells as well as the secretions and metabolites of intestinal flora can then migrate through the intestinal barrier, which will aggravate any peripheral inflammation and the central nervous system injury. The brain-gut-microbiota axis is a complex system that plays a crucial role in the occurrence and development of central nervous system diseases. It may also increase the consequences of preventative treatment. In this context, here we have summarized the factors that can lead to the increased intestinal permeability and some of the possible outcomes.

Tailor-made ternary nanopolyplexes of thiolated trimethylated chitosan with pDNA and folate conjugated cis-aconitic amide-polyethylenimine for efficient gene delivery.

To overcome the different extra-/intracellular barriers in gene delivery, tumor-targeted and pH/redox-responsive ternary polyplexes with charge-conversional properties were prepared through a modular self-assembly strategy. Firstly, the thiolated trimethylated chitosan (TMC-SH) was synthesized to crosslink and condense pDNA through electrostatic interaction and disulfide formation, which obtained the TMC-SS/pDNA binary polyplexes with redox-responsive gene release. To further endow the binary polyplexes with tumor targeting and endo/lysosomal pH-triggered charge-reversal properties, a folate conjugated cis-aconitic amide-polyethylenimine (FA-PEI-AcO) was synthesized to shield the positive TMC-SS/pDNA, generating the FA-PEI-AcO/TMC-SS/pDNA ternary polyplexes with a size of ~190 nm and negative surface-charges. The ζ-potential of the polyplexes was stable at physiological pH and increased rapidly from -14 mV to + 20 mV at pH 5.5 (endo/lysosomal pH) due to the breakages of acid-liable amide bonds and the subsequent de-shielding of FA-PEI-AcO layers, which might benefit the endo/lysosomal escape of the polyplexes. Afterward, the polyplexes could redox-responsively release gene at higher intracellular concentrations of glutathione. By taking advantage of such multi-responses, significantly enhanced transfection efficiency was achieved in vitro in Hela cells for the ternary polyplexes. These results suggested that the newly developed polyplexes had potential application for gene delivery.