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MicroRNAs (miRNAs) are involved in a series of pathology of spinal cord injury (SCI). Although, locally expressed miRNAs have advantages in studying the pathological mechanism, they cannot be used as biomarkers. The "free circulation" miRNAs can be used as biomarkers, but they have low concentration and poor stability in body fluids. Exosomal miRNAs in body fluids have many advantages comparing with free miRNAs. Therefore, we hypothesized that the specific miRNAs in the central nervous system might be transported to the peripheral circulation and concentrated in exosomes after injury. Using next-generation sequencing, miRNA profiles in serum exosomes of sham and subactue SCI rats were analyzed. The results showed that SCI can lead to changes of serum exosomal miRNAs. These changed miRNAs and their associated signaling pathways may explain the pathological mechanism of suacute SCI. More importantly, we found some valuable serum exosomal miRNAs for diagnosis and prognosis of SCI. • Serum exosomes of sham and subactue SCI rats were isolated and identified. • Serum exosomal microRNA transcriptome profiling in subacute spinal cord injured rats is investigated. • The changed miRNAs and their associated signaling pathways have been systematically determined. • Our results will provide a basis for the pathological mechanism, diagnosis and prognosis of SCI. [ABSTRACT FROM AUTHOR]

Previous studies have shown that caspase-1 plays an important role in the acute inflammatory response of spinal cord injury (SCI). VX-765, a novel and irreversible caspase-1 inhibitor, has been reported to effectively intervene in inflammation. However, the effect of VX-765 on genome-wide transcription in acutely injured spinal cords remains unknown. Therefore, in the present study, RNA-sequencing (RNA-Seq) was used to analyze the effect of VX-765 on the local expression of gene transcription 8 h following injury. The differentially expressed genes (DEGs) underwent enrichment analysis of functions and pathways by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively. Parallel analysis of western blot confirmed that VX-765 can effectively inhibit the expression and activation of caspase-1. RNA-Seq showed that VX-765 treatment resulted in 1,137 upregulated and 1,762 downregulated DEGs. These downregulated DEGs and their associated signaling pathways, such as focal adhesion, cytokine-cytokine receptor interaction, leukocyte transendothelial migration, extracellular matrix-receptor interaction, phosphatidylinositol 3-kinase-protein kinase B, Rap1 and hypoxia inducible factor-1 signaling pathway, are mainly associated with inflammatory response, local hypoxia, macrophage differentiation, adhesion migration and apoptosis of local cells. This suggests that the application of VX-765 in the acute phase can improve the local microenvironment of SCI by inhibiting caspase-1. However, whether VX-765 can be used as a therapeutic drug for SCI requires further exploration. The sequence data have been deposited into the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra/PRJNA548970). [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are involved in a series of pathology of spinal cord injury (SCI). Although, locally expressed miRNAs have advantages in studying the pathological mechanism, they cannot be used as biomarkers. The "free circulation" miRNAs can be used as biomarkers, but they have low concentration and poor stability in body fluids. Exosomal miRNAs in body fluids have many advantages comparing with free miRNAs. Therefore, we hypothesized that the specific miRNAs in the central nervous system might be transported to the peripheral circulation and concentrated in exosomes after injury. Using next-generation sequencing, miRNA profiles in serum exosomes of sham and subactue SCI rats were analyzed. The results showed that SCI can lead to changes of serum exosomal miRNAs. These changed miRNAs and their associated signaling pathways may explain the pathological mechanism of suacute SCI. More importantly, we found some valuable serum exosomal miRNAs for diagnosis and prognosis of SCI. [ABSTRACT FROM AUTHOR]

A graph Γ is G -symmetric if G is a group of automorphisms of Γ which is transitive on the set of ordered pairs of adjacent vertices of Γ. If V (Γ) admits a nontrivial G -invariant partition B such that for blocks B , C ∈ B adjacent in the quotient graph Γ B of Γ relative to B , exactly one vertex of B has no neighbour in C , then Γ is called an almost multicover of Γ B. In this case an incidence structure with point set B arises naturally, and it is a (G , 2) -point-transitive and G -block-transitive 2-design if in addition Γ B is a complete graph. In this paper we classify all G -symmetric graphs Γ such that (i) B has block size | B | ≥ 3 ; (ii) Γ B is complete and almost multi-covered by Γ ; (iii) the incidence structure involved is a linear space; and (iv) G contains a regular normal subgroup which is elementary abelian. This classification together with earlier results in Gardiner and Praeger (2018), Giulietti et al. (2013) and Fang et al. (2016) completes the classification of symmetric graphs satisfying (i) and (ii). [ABSTRACT FROM AUTHOR]

We report on a molecular dynamics study of the swelling patterns of an Na-rich/Cs-poor montomorillonite and a Csmontomorillonite. The recently developed CLAYFF force field is used to predict the basal spacing as a function of the water content in the interlayer. The simulations reproduce the swelling patterns of the Na and Cs-montomorillonite, suggesting a mechanism of its hydration different from that of the montomorillonite. In addition, we find that the differences in size and hydration energy of Na and Cs ions have strong implications for the structure and the internal energy of interlayer water. In particular, our results indicate that the hydrate difference in the presence of coexistent Na and Cs has a larger influence on the behavior of a clay-water system. For Na-rich/Cs-poor montomorillonite, the hydration energy values of Na ions and water molecules each have a dramatic increase compared with those in Na-montomorillonite on the interlayer spacing, and the hydration energy values of Cs ions and water molecules decrease somewhat compared with those in Cs-montomorillonite. [ABSTRACT FROM AUTHOR]

Abstract: Additive Hadamard cocycles are a natural generalization of presemifields. In this paper, we study divisible designs and semi-regular relative difference sets obtained from additive Hadamard cocycles. We show that the designs obtained from additive Hadamard cocycles are flag transitive. We introduce a new product construction of Hadamard cocycles. We also study additive Hadamard cocycles whose divisible designs admit a polarity in which all points are absolute. Our main results include generalizations of a theorem of Albert and a theorem of Hiramine from presemifields to additive Hadamard cocycles. At the end, we generalize Maiorana–McFarlandʼs construction of bent functions to additive Hadamard cocycles. [Copyright &y& Elsevier]

Abstract: In this paper we give some necessary and sufficient conditions for Dembowski–Ostrom polynomials to be planar. These conditions give a simple explanation of the Coulter–Matthews and Ding–Yin commutative semifields and enable us to obtain permutation polynomials from some of the Zha–Kyureghyan–Wang commutative semifields. We then give a generalization of Feng’s construction of Paley type group schemes in extra-special -groups of exponent and construct a family of Paley type group schemes in what we call the flag groups of finite fields. We also determine the strong multiplier groups of these group schemes. In the last section of this paper, we give a straightforward generalization of the twin prime power construction of difference sets to a construction of Hadamard designs from twin Paley type association schemes. [Copyright &y& Elsevier]

Abstract: Some cationic antibacterial peptides exhibit a broad spectrum of cytotoxic activity against cancer cells, which could provide a new class of anticancer drugs. In the present study, the anticancer activity of ABP-CM4, an antibacterial peptide from Bombyx mori, against leukemic cell lines THP-1, K562 and U937 was evaluated, and the cytotoxicity compared with the effects on non-cancerous mammalian cells, including peripheral blood mononuclear cells (PBMCs), HEK-293 and erythrocytes. ABP-CM4 reduced the number of viable cells of the leukemic cell lines after exposure for 24h. The reduction was concentration dependent, and the IC50 values ranged from 14 to 18μM. Conversely, ABP-CM4, even at 120μM, exhibited no cytotoxicity toward HEK-293 or PBMCs, indicating that there was no significant effect on these two types of non-cancer cells. ABP-CM4 at a concentration of 200μM had no hemolytic activity on mammalian erythrocytes. Together, these results suggested a selective cytotoxicity in leukemia cells. Flow cytometry demonstrated that the binding activity of ABP-CM4 to leukemia cells was much higher than that to HEK-293 or PBMCs, and there was almost no binding to erythrocytes. FITC-labeled ABP-CM4 molecules were examined under a confocal microscope and found to be concentrated at the surface of leukemia cells and changes of the cell membrane were determined by a cell permeability assay, which led us to the conclusion that ABP-CM4 could act at the cell membrane for its anticancer activity on leukemia cells. Collectively, our results indicated that ABP-CM4 has the potential for development as a novel antileukemic agent. [Copyright &y& Elsevier]

2,5-Dihydroxymethyl-3,6-dimethylpyrazine (liguzinediol) has been recently discovered as a potential agent for treatment of heart failure with low safety risk. In the present study, four main metabolites of liguzinediol were synthesized and their positive inotropic activities were evaluated. Synthetic compounds were identical with the isolated metabolites of liguzinediol. Pharmacological examinations showed that the four major metabolites were not observed positive inotropic activity, and revealed that the positive inotropic activity of liguzinediol was essentially attributed to the parent agent. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we give a characterization of a group G which contains a semiregular relative difference set R relative to a central subgroup N containing the commutator subgroup of G such that and for all . In particular, these relative difference sets are fixed by inversion and inner automorphisms of the group are multipliers. We also present a construction of such relative difference sets. [Copyright &y& Elsevier]

Abstract: It has been reported that it is difficult to express cationic antibacterial peptides in engineered bacteria because such peptides are highly toxic to the host bacteria cells and sensitive to intracellular proteases. Antibacterial peptide CM4 (ABP-CM4) is a small cationic peptide with broad-spectrum activities against bacteria, fungi and tumor cells, which may possibly be used as an antimicrobial agent. Here we tried to express ABP-CM4 in Escherichia coli cells using either the GST fusion system or the intein-mediated fusion expression system. In order to investigate the possible use of these two fusion partners in cationic small peptide expression and purification, a mutant ABP-CMt, which is a highly positively charged peptide with +9 charges at neutral pH, was designed. In the present study, we have shown that both ABP-CM4 and ABP-CMt peptides can be expressed and purified by the intein-mediated expression system but not by the GST fusion expression system. Thus the intein-mediated peptide expression and purification system potentially could be employed for the production of recombinant protease-sensitive and cytotoxic peptides. [Copyright &y& Elsevier]

Abstract: In this paper we prove that an abelian group contains -difference sets with if and only if it contains an elementary abelian 2-group of order . Our proof shows that the method of constructing such difference sets is essentially unique. [Copyright &y& Elsevier]

Abstract: In this paper, we continue our investigation of relative difference sets fixed by inversion. We exclusively focus our attention on abelian groups. New necessary conditions are obtained and a new family of such relative difference sets with forbidden subgroup is constructed. The methods we use are character theory of abelian groups and Galois rings over . [Copyright &y& Elsevier]

Abstract: In this paper, we study the following operator equation: in a Banach space , where is an accretive mapping, is a nonlinear mapping and . Various existence results of solutions of nonlinear operator equations in Banach spaces are obtained under a countably condensing type condition. [Copyright &y& Elsevier]

Abstract: Using graph theoretical technique, we present a construction of a -relative difference set fixed by inversion in the smallest finite simple group—the alternating group . To our knowledge this is the first example known of relative difference sets in the finite simple groups with a non-trivial forbidden subgroup. A connection is then established between some relative difference sets fixed by inversion and certain antipodal distance-regular Cayley graphs. With the connection, several families of antipodal distance-regular Cayley graphs which are coverings of complete graphs are presented. [Copyright &y& Elsevier]

In this paper, we study the existence problem of periodic solutions for the following first-order nonlinear evolution equation u′(t)+A(t)u(t)+Ft,u(t)∋0,t∈R,u(t+T)=u(t),t∈R, in a Hilbert space H, where A is a monotone type operator and F is a nonlinear operator. Existence results are obtained without assuming the coercivity condition. [Copyright &y& Elsevier]

• The pollinia of Anoectochilus roxburghii occurs at the sporogenous cell stage. • A callose wall forms on the pollinium surface, but not inside the pollinium. • A exine forms on the pollinium surface, but not inside the pollinium. The pollen grains of Anoectochilus roxburghii aggregate in pollinia. The aim of this study was to analyse the structural characteristics of pollinium development in A. roxburghii. Features of the pollinia begin to form in the sporogenous cells, in which some cell walls begin to differentiate to form the outline of the pollinia. During development of the microspore mother cells (MMCs), the nucleus and organelles penetrate the cell walls (cytomixis) between MMCs within a pollinium, but not between the MMCs among different pollinia. A thick callose wall forms on the surface of the pollinia, but not between MMCs inside the pollinium. After meiosis, a sporopollenin exine forms on the surface of the pollinia, but not on the surface of pollen grains inside the pollinium. The mature pollen of A. roxburghii is bicellular and consists of a vegetative cell and a generative cell. [ABSTRACT FROM AUTHOR]

This article discusses a study that examines the genetic and molecular characteristics of lung cancer patients who have transformed from one type of lung cancer to another. The study identifies two distinct subtypes based on the RB1 gene status of the patients. The findings suggest that RB1 and SMAD4 alterations are important factors in this transformation, and patients with RB1 mutations tend to have a longer time before the transformation occurs. The article highlights the importance of understanding the heterogeneity within this patient population in order to develop new treatments and improve outcomes. Additionally, the study develops a predictive model to assess the risk of transformation in patients with specific gene mutations. Overall, this research provides valuable insights into the biology of transformed lung cancer and potential targets for therapy. [Extracted from the article]

By evaporating the MoSe 2 compounds using an electron gun evaporator, three layers of MoSe 2 was vertically stacked on graphene via van der Waals epitaxy. • MoSe 2 /graphene vertical heterostructure film with wafer-scale continuous was realized by a new method involving PVD. • Three layers of MoSe 2 grown on graphene via van der Waals epitaxy was identified. • The interface interaction between graphene and the MoSe 2 epilayer was inspected by Raman spectroscopy. Two-dimensional MoSe 2 /graphene heterostructure in a wafer-scale was realized by a new method involves physical vapor deposition (PVD), in which the MoSe 2 film was vertically stacked on graphene by evaporating the MoSe 2 compounds using an electron gun evaporator. A preferred lattice orientation with the underlying graphene was identified by transmission electron microscopy, revealing the van der Waals epitaxy (VdWs) of MoSe 2. The interface interaction between the graphene substrate and the MoSe 2 epilayer was investigated via Raman spectroscopy. The growth technique provides a facile route to create large area VdWs heterostructures, which can be developed for future mass production of nano-devices. [ABSTRACT FROM AUTHOR]

Background: After spinal cord injury (SCI), destructive immune cell subsets are dominant in the local microenvironment, which are the important mechanism of injury. Studies have shown that inflammasomes play an important role in the inflammation following SCI, and apoptosis-associated speck-like protein containing a card (ASC) is the adaptor protein shared by inflammasomes. Therefore, we speculated that inhibiting ASC may improve the local microenvironment of injured spinal cord. Here, CRID3, a blocker of ASC oligomerization, was used to study its effect on the local microenvironment and the possible role in neuroprotection following SCI.Methods: Murine SCI model was created using an Infinite Horizon impactor at T9 vertebral level with a force of 50 kdynes and CRID3 (50 mg/kg) was intraperitoneally injected following injury. ASC and its downstream molecules in inflammasome signaling pathway were measured by western blot. The immune cell subsets were detected by immunohistofluorescence (IHF) and flow cytometry (FCM). The spinal cord fibrosis area, neuron survival, myelin preservation, and functional recovery were assessed.Results: Following SCI, CRID3 administration inhibited inflammasome-related ASC and caspase-1, IL-1β, and IL-18 activation, which consequently suppressed M1 microglia, Th1 and Th1Th17 differentiation, and increased M2 microglia and Th2 differentiation. Accordingly, the improved histology and behavior have also been found.Conclusions: CRID3 may ameliorate murine SCI by inhibiting inflammasome activation, reducing proinflammatory factor production, restoring immune cell subset balance, and improving local immune microenvironment, and early administration may be a promising therapeutic strategy for SCI. [ABSTRACT FROM AUTHOR]

In this paper, we consider regular automorphism groups of graphs in the RT2 family and the Davis‐Xiang family and amorphic abelian Cayley schemes from these graphs. We derive general results on the existence of non‐abelian regular automorphism groups from abelian regular automorphism groups and apply them to the RT2 family and Davis‐Xiang family and their amorphic abelian Cayley schemes to produce amorphic non‐abelian Cayley schemes. [ABSTRACT FROM AUTHOR]

In this paper, the dispersion properties of three-dimensional function magnetized plasma photonic crystals (FMPPCs) are theoretically studied by a modified plane wave expansion method, when the magneto-optical Faraday effect is considered, and the directions of the electromagnetic wave vector and the extrinsic magnetic field are always parallel to each other. The arrangement of these FMPPCs is that the function dielectric square columns are embedded into the plasma background, and the inserted dielectric columns are arranged by woodpile lattices with face-centered-tetragonal symmetry. The relative permittivity of function square columns depends on the space coordinates. The relationships between the parameters of FMPPCs and the photonic bandgaps (PBGs) for the right and left circular polarization waves also are investigated. The calculated results demonstrate that those PBGs can be tailored by those parameters, and the right and left circular polarization waves can be split when the extrinsic magnetic field is large enough. [ABSTRACT FROM AUTHOR]

Farmers' participation in food safety governance is an important part of food safety social co-governance, and the accurate identification of its influencing factors and their related paths is of guiding significance to the scientific decision-making of food safety governance. The system of influencing factors of farmers' participation in food safety governance was constructed from four dimensions, and the influence network of each dimension was revealed by decision laboratory analysis (DEMATEL). The hierarchical structure and correlation path of influencing factors were determined by interpretive structural model (ISM), and the attributes of influencing factors were further classified by cross influence matrix multiplication (MICMAC). The results show that the influencing factors of farmers' participation in food safety governance can be divided into seven levels, among which the level of education and the status of village cadres are the fundamental characteristic factors. The degree of rural informatization, the intensity of government supervision, the promotion of village committees, the response of the government and the degree of disclosure of government information are the deep core factors, and risk cognition, political trust and family eating habits are special factors. Taking the importance and attribute status of farmers' participation in food safety governance into decision-making considerations is of great significance to improve the efficiency of food safety governance. [ABSTRACT FROM AUTHOR]

Background:Limb-girdle muscular dystrophy type 2I (LGMD2I) is an autosomal recessive hereditary disorder caused by mutations in the fukutin-related protein (FKRP) gene. Although the features of the disorder in European patients have been summarized, Asian patients with LGMD2I have rarely been reported. Thus, the clinical differences in LGMD2I between Asian and European patients and the associated genetic changes remain unclear. Methods:We reported detailed clinical data as well as results from muscle biopsy, muscle MRI and genetic analysis of theFKRPgene in two unrelated Chinese families with LGMD2I. Additionally, a review of the literature focusing on the clinical and mutational features of LGMD2I in Asian patients was performed. Results:The muscle biopsy results showed dystrophic features. Immunohistochemical staining revealed decreased glycosylations on α-dystroglycan. The muscle MRI results showed that the gluteus maximus, adductor, biceps femoris, vastus intermedius and vastus lateralis were severely affected. The patients in the two families harbored the same compound heterozygous mutations (c.545A>G and c.948delC). One patient showed significant clinical improvement after corticosteroid treatment. Conclusion:Our study expanded the reported spectrum of Asian LGMD2I patients. Our literature review revealed that pathogenic mutations in theFKRPgene in Asian LGMD2I patients are compound heterozygous rather than homozygous. Compound heterozygous Asian patients have a mild phenotype but frequently show respiratory and cardiac impairments. Corticosteroids may be beneficial for the treatment of LGMD2I and should be further investigated. [ABSTRACT FROM AUTHOR]

• The ORR of ABCP/ECT for T -SCLC exceeds 70 %, with a mPFS of 5.1 m. • PD-L1 inhibitor-based combination therapy significantly prolonged pOS of T -SCLC. • Combination immunotherapy could serve as a potential treatment option for T -SCLC. • Upregulation of SFTPA1, EGFR L858R, or PD-L1 ≥ 1 % may benefit these patients. Transformed small-cell lung cancer (T -SCLC) has an extremely poor prognosis, and no remedies based on immunotherapy have been evaluated among T -SCLC patients. We retrospectively analysed the efficacy and safety of combining atezolizumab with chemotherapy for T -SCLC. Forty-seven patients harbouring EGFR mutations who developed T -SCLC were enrolled. Eleven patients who used immunotherapy were defined as the I/O group, and the remaining 36 were defined as the Non-I/O group. Clinical characteristics, pathological data, and survival outcomes were collected. RNA sequencing and whole-exome sequencing (WES) were performed for in-depth analysis. All patients received at least one line of EGFR-TKI before rebiopsy to confirm T -SCLC. Nine patients received atezolizumab-bevacizumab-carboplatin-paclitaxel (albumin-bound) (ABCP), and the remaining 2 received atezolizumab-etoposide-carboplatin (ECT) in the I/O group. The objective response rate was 73 % (8/11). The median progression-free survival (mPFS) of T -SCLC on post-transformation therapy with I/O group and Non-I/O group was 5.1 m and 4.1 m, respectively. The median post- T -SCLC overall survival of the I/O group was significantly longer than that Non-I/O group (20.2 m vs 7.9 m, P ＜ 0.01). T -SCLC harbouring EGFR L858R tended to be longer than EGFR 19del (mPFS: not reached vs 3.7 m, P = 0.11). Positive PD-L1 status was also associated with PFS benefits (mPFS: 6.0 m vs 3.7 m, P = 0.20). Furthermore, RNA sequencing revealed that expression of SFTPA1 is significantly higher in the durable clinical benefit group. WES showed that STC2 mutation is more frequently observed at the time-point immunotherapy acquired resistance. Combination therapy based on a PD-L1 inhibitor was well tolerated, and the safety profile was consistent with previously reported studies. Our study first demonstrated that a PD-L1 inhibitor combined with chemotherapy ± bevacizumab could be a potential safe option for specific SCLC-transformed patients. Subsequent studies with more patients are essential to verify the efficacy and potential biomarkers. [ABSTRACT FROM AUTHOR]

A simple liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI/MS) method has been developed to analyze oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (ox-PAPC) products on the lipoproteins of uremic patients. The native PAPC standard was in vitro oxidized by the Fenton reaction, and the ox-PAPC products were analyzed by LC- ESI/MS. For LC, a C8 column and a mobile phase (acetonitrile-isopropanol containing 0.1% formic acid (70:30, v/v)) were selected. For ESI/MS, the optimal conditions included sheath gas pressure (10 psi), capillary temperature (270 °C), and injection time (1000 ms). The identification of ox-PAPC products on human lipoproteins was based on the extracted ion chromatograms (EICs) and the ESI-MS spectra of the in vitro oxidation products of PAPC standard. The EICs and ESI-MS spectra showed good repeatability and sensitivity. A total of 21 ox-PAPC products was determined. Linear analysis has been performed for the phospholipid standard, 1, 2-Di-O-hexadecyl-sn-glycero-3-phosphocholine (PC(O-16:0/O-16:0)). The linear range was 5.0–100.0 µg/mL, and the coefficient of determination (R2) was 0.989. The concentration limit of detection (LOD) was 1.50 µg/mL, and the concentration limit of quantitation (LOQ) was 4.54 µg/mL. The selected 21 ox-PAPC products have been identified and quantified in very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) of uremic and healthy subjects. Interestingly, the results showed that the levels of 18 products in VLDL, one product in LDL, and 19 products in HDL were significantly higher for uremic patients than healthy controls. This simple LC-ESI/MS method might accelerate the searching for biomarkers of uremia in the future. [ABSTRACT FROM AUTHOR]

Lung cancer is the most malignant form of cancer and has the highest morbidity and mortality worldwide. Due to drug resistance, the current chemotherapy for lung cancer is not effective and has poor therapeutic effects. Tripchlorolide (T4), a natural extract from the plant Tripterygium wilfordii, has powerful immunosuppressive and antitumour effects and may become a potential therapeutic agent for lung cancer. Therefore, this study aimed to investigate the effect of T4 on reducing chemoresistance in lung cancer cells and to explore the mechanism. 1. A549 and A549/DDP cells were separately transfected with AEG-1 overexpression and AEG-1 knockdown plasmids. A549/DDP cells were divided into the A549/DDP empty group, T4 group, and T4 + AEG-1 overexpression group. A CCK-8 assay was used to evaluate the proliferation of cells in each group. RT–qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1. Expression of AEG-1 in A549 and A549/DDP cells was positively correlated with cisplatin resistance. When the AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P < 0.05). After the AEG-1 protein was knocked down in A549/DDP cells, cisplatin was applied. The lethal effect was significantly increased compared to that in the corresponding control cells (all P < 0.05). AEG-1 protein expression gradually decreased with increasing T4 concentration in A549 and A549/DDP cells. Resistance to cisplatin was reduced after the addition of T4 to A549/DDP cells (P < 0.05), and this effect was enhanced after transfection with the AEG-1 knockdown plasmid. T4 plays an important role in increasing the sensitivity of lung cancer cells to cisplatin. [ABSTRACT FROM AUTHOR]

Lung cancer is the most malignant form of cancer and has the highest morbidity and mortality worldwide. Due to drug resistance, the current chemotherapy for lung cancer is not effective and has poor therapeutic effects. Tripchlorolide (T4), a natural extract from the plant Tripterygium wilfordii, has powerful immunosuppressive and antitumour effects and may become a potential therapeutic agent for lung cancer. Therefore, this study aimed to investigate the effect of T4 on reducing chemoresistance in lung cancer cells and to explore the mechanism. 1. A549 and A549/DDP cells were separately transfected with AEG-1 overexpression and AEG-1 knockdown plasmids. A549/DDP cells were divided into the A549/DDP empty group, T4 group, and T4 + AEG-1 overexpression group. A CCK-8 assay was used to evaluate the proliferation of cells in each group. RT–qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1. Expression of AEG-1 in A549 and A549/DDP cells was positively correlated with cisplatin resistance. When the AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P < 0.05). After the AEG-1 protein was knocked down in A549/DDP cells, cisplatin was applied. The lethal effect was significantly increased compared to that in the corresponding control cells (all P < 0.05). AEG-1 protein expression gradually decreased with increasing T4 concentration in A549 and A549/DDP cells. Resistance to cisplatin was reduced after the addition of T4 to A549/DDP cells (P < 0.05), and this effect was enhanced after transfection with the AEG-1 knockdown plasmid. T4 plays an important role in increasing the sensitivity of lung cancer cells to cisplatin. [ABSTRACT FROM AUTHOR]

Background: MET dysregulation has been implicated in the development of primary and secondary resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. However, the clinicopathological characteristics and outcomes of patients harboring EGFR‐sensitive mutations and de novo MET amplifications still need to be explored. Methods: A total of 54 patients from our hospital with non‐small cell lung cancer harboring EGFR‐sensitive mutations and/or de novo MET amplifications were included in this study. Survival rates were estimated by the Kaplan–Meier method with log‐rank statistics. Lung cancer organoids (LCOs) were generated from patient‐derived malignant pleural effusion to perform drug sensitivity assays. Results: Fifty‐four patients with the appropriate clinicopathological characteristics were enrolled. MET FISH was performed in 40 patients who were stratified accordingly into two groups: EGFR+/METamp‐ (n = 22) and EGFR+/METamp + (n = 18). Survival rates for EGFR+/METamp‐ and EGFR+/METamp + patients respectively, were as follows: the median progression‐free survival (PFS) was 12.1 and 1.9 months (p<0.001); the median post‐progression overall survival (pOS) was 25.6 and 11.6 months (p = 0.023); the median overall survival (OS) was 33.2 and 12.7 months (p = 0.013). Drug testing conducted in LCOs derived from malignant pleural effusion from EGFR+/METamp + patients showed that dual targeted therapy was more effective than TKI monotherapy. Conclusion: EGFR+/METamp + patients treated with first‐line TKI monotherapy had poor clinical outcomes. Dual targeted therapy showed potent anticancer activity in the LCO drug testing assay, suggesting that it is a promising first‐line treatment for EGFR+/METamp + patients. Randomized controlled trials are needed to further validate these results. [ABSTRACT FROM AUTHOR]

Apoptosis associated speck like protein containing a card (ASC), the key adaptor protein of the assembly and activation of canonical inflammasomes, has been found to play a significant role in neuroinflammation after spinal cord injury (SCI). The previous studies indicated that widely block or knockout ASC can ameliorate SCI. However, ASC is ubiquitously expressed in infiltrated macrophages and local microglia, so further exploration is needed on which type of cell playing the key role. In this study, using the LysMcre;Ascflox/flox mice with macrophage-specifc ASC conditional knockout (CKO) and contusive SCI model, we focus on evaluating the specific role of ASC in lysozyme 2 (LysM)+ myeloid cells (mainly infiltrated macrophages) in this pathology. The results revealed that macrophage-specifc Asc CKO exhibited the follow effects: (1) A significant reduction in the numbers of infiltrated macrophages in the all phases of SCI, and activated microglia in the acute and subacute phases. (2) A significant reduction in ASC, caspase-1, interleukin (IL)-1β, and IL-18 compared to control mice. (3) In the acute and subacute phases of SCI, M1 subset differentiation was inhibited, and M2 differentiation was increased. (4) Histology and hindlimb motor recoveries were improved. In conclusion, this study elucidates that macrophage-specific ASC CKO can improve nerve function recovery after SCI by regulating M1/M2 polarization through inhibiting ASC-dependent inflammasome signaling axis. This indicates that ASC in peripheral infiltrated macrophages may play an important role in SCI pathology, at least in mice, could be a potential target for treatment. [Display omitted] • Asc CKO can reduce the infiltration of macrophages after SCI in mice. • Asc CKO can reduce the activated microglia in the acute and subacute phases of SCI. • Asc CKO can inhibit ASC-dependent inflammasome signaling axis. • Asc CKO can inhibit M1 polarization, and increase M2 polarization. • Asc CKO can improve histology and hindlimb motor recoveries after SCI. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, an omnidirectional photonic band gap (OBG) which originates from Bragg gap compared to gap or single negative (negative permittivity or negative permeability) gap, is realized by one-dimensional (1D) superconductor-dielectric photonic crystals (SDPCs) with ternary Thue–Mores aperiodic structure, which is composed of superconductor and two kinds of homogeneous, isotropic dielectric is theoretically investigated by the transfer matrix method (TMM) in detail. Such OBG is insensitive to the incident angle and the polarization of electromagnetic wave (EM wave). From the numerical results, the bandwidth and central frequency of OBG can be notably enlarged by tuning the thickness of superconductor and dielectric layers but cease to change with increasing Thue–Mores order. The OBG also can be manipulated by the ambient temperature of system especially close to the critical temperature. Moreover, the damping coefficient of superconductor has no effect on the bandwidth of OBG under low-temperature condition. These results may provide theoretical instructions to design the future optoelectronic devices based on superconductor. [Copyright &y& Elsevier]

Inflammation is one of the key injury factors for spinal cord injury (SCI). Exosomes (Exos) derived from M2 macrophages have been shown to inhibit inflammation and be beneficial in SCI animal models. However, lacking targetability restricts their application prospects. Considering that chemokine receptors increase dramatically after SCI, viral macrophage inflammatory protein II (vMIP-II) is a broad-spectrum chemokine receptor binding peptide, and lysosomal associated membrane protein 2b (Lamp2b) is the key membrane component of Exos, we speculated that vMIP-II-Lamp2b gene-modified M2 macrophage-derived Exos (vMIP-II-Lamp2b-M2-Exo) not only have anti-inflammatory properties, but also can target the injured area by vMIP-II. In this study, using a murine contusive SCI model, we revealed that vMIP-II-Lamp2b-M2-Exo could target the chemokine receptors which highly expressed in the injured spinal cords, inhibit some key chemokine receptor signaling pathways (such as MAPK and Akt), further inhibit proinflammatory factors (such as IL-1β, IL-6, IL-17, IL-18, TNF-α, and iNOS), and promote anti-inflammatory factors (such as IL-4 and Arg1) productions, and the transformation of microglia/macrophages from M1 into M2. Moreover, the improved histological and functional recoveries were also found. Collectively, our results suggest that vMIP-II-Lamp2b-M2-Exo may provide neuroprotection by targeting the injured spinal cord, inhibiting some chemokine signals, reducing proinflammatory factor production and modulating microglia/macrophage polarization. [Display omitted] • vMIP-II-Lamp2b-M2-Exo can target the injured spinal cord by vMIP-II. • vMIP-II-Lamp2b-M2-Exo can inhibit MAPK and AKT signaling pathways. • vMIP-II-Lamp2b-M2-Exo can reduce proinflammatory factor production. • vMIP-II-Lamp2b-M2-Exo can inhibit M1 microglia/macrophage polarization. • The early administration of vMIP-II-Lamp2b-M2-Exo is a promising strategy for SCI. [ABSTRACT FROM AUTHOR]

Aim: Hydroxychloroquine (HCQ) is used to control proteinuria in IgA Nephropathy (IgAN) However, its efficacy and safety in pregnant IgAN patients remains unknown. This study aimed to verify the safety of HCQ in pregnant IgAN patients and compare renal function and pregnancy outcomes with those of patients not treated with HCQ. Methods: We retrospectively reviewed medical records of all pregnant IgAN patients and singleton gestations at Peking University First Hospital from 2003–2021. Patients who did and did not receive HCQ treatment during pregnancy were compared. Results: We found no significant pre‐ or post‐pregnancy differences in proteinuria or renal function between the two groups. However, the HCQ (+) group had higher proteinuria at the time of kidney biopsy (2.04 [1.26, 2.56] g/d vs. 0.80 [0.44, 1.11] g/d, P <.001); the proteinuria level at HCQ therapy initiation was also higher than that at the beginning of pregnancy (1.87 [1.30, 2.59] g/d vs. 1.08 [0.75, 1.50] g/d, P =.001). Despite no difference in preterm birth, birth weight, preeclampsia or postpartum haemorrhage, the proportion of patients with a previous history of spontaneous abortion was higher in the HCQ (+) group than in the HCQ (−) group (48.0% vs. 20.6%, P =.010). The eGFR (regression coefficient, 0.981; 95%CI 0.964–0.998) was a predictive factor for obstetrical complications. Conclusion: HCQ is safe for IgAN treatment during pregnancy with effective reduction of proteinuria. HCQ might also be helpful in patients with a history of spontaneous abortion. SUMMARY AT A GLANCE: In this retrospective comparison of 25 pregnant patients with IgA nephropathy treated with hydroxychloroquine (HCQ) versus 65 other pregnant IgAN patients who were not given HCQ, it was found that HCQ is safe and effective in reducing proteinuria. Multivariate regression shows that baseline eGFR is a predictor of obstetric complications. [ABSTRACT FROM AUTHOR]

The properties of the reflectance for a superconductor multilayer structure with periodically varying ambient temperature have been theoretically investigated by the transfer matrix method (TMM). From the numerical results, it has been shown that such system has the photonic band gap (PBG) properties of photonic crystals (PCs), so it can also be called superconductor photonic crystals (SPCs). It is found that the locations and bandwidths of PBGs can be modulated by the incident angle. The frequency ranges and central frequencies of PBGs can be tuned by the temperature and thickness of superconductor layer A (higher temperature superconductor layer), respectively. The bandwidths of PBGs can be notably enlarged with increasing the temperature of superconductor layer A. The frequency ranges of PBGs can be controlled by increasing the thickness of superconductor layer A, and the more PBGs appear. The damping coefficient of superconductor and the number of periods have little effect on the bandwidths of PBGs under low-temperature conditions. It is shown that this kind of SPCs has potential applications in filters, microcavities, and fibers, etc. [ABSTRACT FROM AUTHOR]

Abstract: Background: To assess the prognosis value of cyclin E expression in survival of patients with lung cancer (LC), we performed a systematic review of the literature with meta-analysis. Methods: Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95% confidence interval (95% CI) was used to estimate the strength of the association of cyclin E expression with survival of LC patients. Heterogeneity and publication bias were also assessed. Results: Fourteen studies (2606 cases) were eligible and subjected to analysis. Cyclin E over-expression was found to be a strong predictor of poor prognosis in LC patients (HR: 1.38, 95% CI: 1.07–1.79; P=0.014). When only non-small cell lung cancer (NSCLC) was considered, the combined HR was 1.53 (95% CI: 1.19–1.97, P=0.001). A significant association was also evident when the analysis was limited to studies involving adenocarcinoma (AD), but not squamous cell carcinoma (SQ). Publication bias was absent. Sensitivity analyses suggested that the summary statistics obtained should approximate the actual average. [Copyright &y& Elsevier]

This research applies experimental measurements and NUBEAM, ONETWO and TRANSP modules to investigate the shine-through (ST) loss ratio and beam heating percentage of neutral beam injection on EAST. Measurements and simulations confirm that the ST loss ratio increases linearly with beam energy, and decreases exponentially with plasma density. Moreover, using the multi-step fitting method, we present analytical quantitative expressions of ST loss ratio and beam heating percentage, which are valuable for the high parameter long-pulse experiments of EAST. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to investigate the influence of diagnosis, body weight, sex, age, smoking, formulations, and concomitant drugs on steady‐state dose‐corrected serum concentrations (C/D) of venlafaxine (VEN) and O‐desmethylvenlafaxine (ODV). Methods: A retrospective analysis of therapeutic drug monitoring (TDM) was carried out. Patients' demographic data, therapeutic regimens, and concentrations were collected. Results: We included 91 verified samples from 80 patients. Females had by average 13% smaller body weight, 50% higher C/D of VEN, and VEN + ODV and 25% smaller ODV/VEN than males. Patients >60 years had by average 33–59% higher C/D levels of ODV and VEN + ODV than younger patients. The concomitant use of valproic acid caused an average 51% higher C/D of ODV and a 2.2‐fold larger ODV/VEN, while clozapine was related with 40% smaller ratio of ODV/VEN and 38% lower C/D levels of ODV. Positive correlations were detected between valproic acid concentrations and the C/D of VEN and VEN + ODV. In a multiple linear regression analysis, variance in the C/D of VEN + ODV was partly attributed to the daily dose of VEN, sex, age and valproic acid concentration. Conclusion: Our results suggested daily dose of VEN, sex, age, and valproic acid as indicators for the C/D of VEN + ODV in Chinese patients. TDM as a valuable tool was suggested in elderly female patients and patients receiving polypharmacy. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, the cDNA of Père David’s deer APRIL (miAPRIL) was successfully amplified, and nucleotide sequence analysis showed that the open reading frame (ORF) of miAPRIL consists of 753 bases encoding 250-amino acids. Phylogenetic analysis exhibited high homology with the even-toed ungulates (artiodactyla). The extracellular soluble domain of the miAPRIL (misAPRIL) fragment was cloned into the expression vector pET43.1a and transformed into Escherichia coli BL21 (DE3) for recombinant expression. SDS–PAGE and western blotting analysis indicated that misAPRIL protein expression was successfully achieved. Indirect immunofluorescence staining demonstrated that misAPRIL has the ability to bind to the surface of Père David’s deer lymphocytes. Flow cytometry analysis revealed that misAPRIL was able to enhance lymphocytes survival in a dose-dependent manner. [Copyright &y& Elsevier]

Background/Aims: Cognitive impairment and abnormal structural neuroimaging is common in chronic kidney disease patients. We aimed to explore its association with dialysis modality and the relationship between cognitive impairment and abnormal structural neuroimaging. Methods: Sixty peritoneal dialysis patients and 30 hemodialysis and 30 non-dialyzed stage 3-5 chronic kidney disease patients without history of stroke were enrolled for the study. Participants were matched for age, gender, education, diabetes status, and dialysis duration (if appropriate). Cognitive functions were measured using a battery of recognized instruments. Brain features were examined with 3-dimensional magnetic resonance imaging. Results: Cognitive impairment was significantly more severe in dialysis patients than in non-dialyzed patients. The global and specific cognitive function were not significantly different between patients on peritoneal dialysis and hemodialysis. Hemodialysis patients had more severe white matter hyperintensity, sulcal and ventricular atrophy, and SVIs than other patients. In all groups, higher white matter grade, ventricular grade, and hippocampal atrophy were significantly associated with global cognitive impairment, with hazard ratios of 1.80 (1.22-2.64), 1.67 (1.09-2.57), and 2.49 (1.07-5.77), respectively. White matter grade was also significantly associated with delayed memory (hazard ratio 1.63; 1.12-2.39). Conclusion: Dialysis modality showed no association with cognitive impairment, although hemodialysis patients had more severe neuroimaging abnormalities. For the whole group, white matter hyperintensity, and ventricular and hippocampal atrophy, were independently associated with global cognitive impairment in chronic kidney disease patients. [ABSTRACT FROM AUTHOR]

Background: To investigate the role of CD138 immunohistochemistry in the diagnosis of chronic endometritis (CE) and the risk factors for assisted conception patients having CE complications.Methods: Ninety-three patients, with normal uterine shape confirmed by examination and who were planning to undergo assisted conception treatments, were selected as research subjects. Endometrial tissue was isolated for routine hematoxylin and eosin (HE) and CD138 immunohistochemical staining. Additionally, the disease histories of patients were collected, and the reproductive prognosis was followed up.Results: ① CE detection rate: The rate of CD138 immunohistochemical staining was greater than that of HE staining (27.96 % vs. 26.89 %, P <0.05); ② Pregnancy rate: the pregnancy rate of CD138-positive patients (7.7 %) was lower than the pregnancy rate of CD138-negative patients (31.3 %) (p = 0.017 < 0.05); ③ The results from univariate analysis showed that a previous history of prolonged menstrual bleeding episodes, an abortion history, and complications of fallopian tube obstruction were associated with CE (P <0.05). The results of logistic regression analysis confirmed that prolonged menstrual bleeding episodes (P = 0.014, OR = 5.394, 95 % CI 1.405-20.699), a previous abortion history (P = 0.029, OR = 3.194, 95 % CI 1.125-9.073), and fallopian tube obstruction (P = 0.028, OR = 3.274, 95 % CI 1.139-9.415) were independent risk factors for positive CD138 results.Conclusions: CD138 immunohistochemistry can improve the CE diagnosis rate. A previous history of prolonged menstrual bleeding episodes, an abortion history, and a history of fallopian tube obstruction are risk factors for chronic endometritis, and a CD138 immunohistochemical examination should be advised among them. [ABSTRACT FROM AUTHOR]

Abstract: Antibacterial peptides (ABPs) with cancer-selective toxicity have received much more attention as alternative chemotherapeutic agents in recent years. However, the basis of their anticancer activity remains unclear. The modification of cell surface glycosylation is a characteristic of cancer cells. The present study investigated the effect of glycosylation, in particular sialic acid, on the anticancer activity of ABPs. We showed that aurein 1.2, buforin IIb and BMAP-28m exhibited selective cytotoxicity toward MX-1 and MCF-7 breast cancer cells. The binding activity, cytotoxicity and apoptotic activity of ABPs were enhanced by the presence of O-, N-glycoproteins, gangliosides and sialic acid on the surface of breast cancer cells. Among N-, O-glycoproteins and ganglioside, O-glycoproteins almost had the strongest effect on the binding and cytotoxicity of the three peptides. Further, up-regulation of hST6Gal1 in CHO-K1 cells enhanced the susceptibility of cells to these peptides. Finally, the growth of MX-1 xenograft tumors in mice was significantly suppressed by buforin IIb treatment, which was associated with induction of apoptosis and inhibition of vascularization. These data demonstrate that the three peptides bind to breast cancer cells via an interaction with surface O-, N-glycoproteins and gangliosides. Sialic acids act as key glycan binding sites for cationic ABP binding to glycoproteins and gangliosides. Therefore, glycosylation in breast cancer cells plays an important role in the anticancer activity of ABPs, which may partly explain their cancer-selective toxicity. Anticancer ABPs with cancer-selective cytotoxicity will be promising candidates for anticancer therapy in the future. [Copyright &y& Elsevier]

We report a 41-year-old Chinese female with Fabry disease and diffuse thinning of the glomerular basement membrane (GBM). The patient presented with peripheral edema, mild proteinuria, microscopic hematuria, normal renal function, hypertension and tinnitus. Family screening showed that her daughter had microscopic hematuria, tinnitus and neuropathic pain. Renal biopsy of the proband showed focal segmental glomerulosclerosis with cytoplasmic vacuolization of the glomerular visceral epithelial cells by light microscopy. Laminated myelin inclusions in some of the glomerular podocytes, parietal epithelia, distal tubular epithelial cells and vascular endothelial cells along with diffuse thinning of the GBM (mean thickness of GBM: 216 ± 31 nm) were identified by electron microscopy. Genetic analysis detected a de novo novel GLA mutation, 1208 ins 21 bp, while a new variant of COL4A3 SNP M1209I was carried by mother and daughter as well as the proband’s father (I-1) and one sister (II-4). The coexistence of thinned GBM should be considered in patients with Fabry disease-manifested familial hematuria. [ABSTRACT FROM AUTHOR]

Abstract: Lipopolysaccharide (LPS) is a major constituent of the outer membrane of Gram-negative bacteria. Binding of LPS to the CD14+ murine macrophage cell line RAW264.7 results in pro-inflammatory cytokine secretion. In extreme cases, it leads to septic shock in vivo. Therefore, the pursuit for molecules with antiendotoxin properties is urgent. In this study, we investigated the efficacy of antibacterial peptide CM4 in binding Escherichia coli LPS in vitro. CM4 avidly bound to E. coli LPS, as proven by the limulus amoebocyte lysate assay. Furthermore, the killing activity of CM4 against E. coli was progressively inhibited by increasing concentrations of LPS added to the medium, further confirming the peptide''s affinity for endotoxin. Flow cytometric analysis revealed that CM4 inhibited the binding of FITC-conjugated LPS to RAW264.7 cells. Likewise, the inhibition of peptide to LPS-dependent cytokine induction was analyzed. CM4 suppressed LPS-induced TNF-α and IL-6 mRNA expression and blocked release of TNF-α and NO following LPS challenge in RAW264.7 cells. Together these observations indicate that antibacterial peptide CM4 probably exerts protective actions against endotoxin shock by blocking the binding of LPS to CD14+ cells. [Copyright &y& Elsevier]

Abstract: Antibacterial peptides CM4 (ABP-CM4) is a linear cationic peptide that has antimicrobial properties. To explore a new approach of expression of ABP-CM4 in methylotrophic yeast Pichia pastoris, the gene of ABP-CM4 was obtained by recursive PCR (rPCR) and cloned into the vector pPICZaA. The SacI-linearized plasmid pPICZaA-CM4 was transformed into P. pastoris GS115 by electroporation. The expression was induced about 72h with 0.5% methanol at 20°C, supplied with 2% casamino acids to avoid proteolysis, and approximately 40mg ABP-CM4 was secreted into 1L of medium. Recombinant ABP-CM4 was purified through size-exclusion chromatography and 15mg pure active ABP-CM4 was obtained from 1L culture. Tricine–SDS–PAGE indicated that recombinant ABP-CM4 was secreted as a protein of around 3.8kDa. The recombinant ABP-CM4 appears to be successfully expressed, as it displays antibacterial and antifungal activity (antibacterial assay, polyarylamide gel electrophoresis, and antifungal assay) indistinguishable from those of natural protein. [Copyright &y& Elsevier]

In this article, a multilayer dielectric antenna with an air layer is used to realize a strain sensor, which can be utilized to measure the pressure. The springs are sandwiched between a parasitic plate and the designed antenna, where an air layer exists. The pressure can be measured by the relationship between the thickness of the air layer and the S‐parameter of the designed antenna. When the springs are deformed within a certain range, the center frequency of the designed antenna (S‐parameter is less than −10 dB) is correlated with the length of deformation, which can be marked by the thickness of the air layer between the parasitic patch and the antenna. The influence of the air layer thickness on the S‐parameter of this antenna is investigated. The results show that the deformation of the springs has an approximate linear relationship with the center frequency of return loss. The design provides a new idea about stress measurement. [ABSTRACT FROM AUTHOR]