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Background and aims: The effect of dapagliflozin (DAPA) on the prognosis of patients with acute myocardial infarction (AMI) is unclear. The present study was conducted to evaluate the association between DAPA administration and adverse events in patients with AMI undergoing percutaneous coronary intervention (PCI). Methods: This single-center retrospective analysis study included a total of 786 patients with AMI from January 2019 to August 2021 who were or were not administered DAPA at discharge. The primary endpoint was the composite of major adverse cardiovascular events (MACE), including overall deaths, heart failure, nonfatal MI, nonfatal stroke, and unplanned repeat revascularization (URR). Differences in the triglyceride glucose (TyG) index and the atherogenic index of plasma (AIP) both during hospitalization and 12 months after discharge (if achievable) were also compared. Results: During a median follow-up of 23 months, 130 patients had MACE (118 in the DAPA-free group and 12 in the DAPA group). Kaplan–Meier survival analyses revealed that the cumulative incidence of MACE (log-rank test, p = 0.009), heart failure (p = 0.003), nonfatal MI (p = 0.005), and URR (p = 0.031) was higher in the DAPA-free group. In addition, the multivariate Cox analysis showed that DAPA was significantly associated with the reduced risk of MACE (hazard ratio = 0.170, 95% confidence interval = 0.078–0.373, p < 0.001). Considering each specific adverse event, the DAPA-free group was associated with heart failure, nonfatal MI, and URR in multivariate Cox regression analyses. Stratification analyses suggested that DAPA has a strong protective effect in patients with AMI of advanced age with concomitant diabetes or those who are not on angiotensin receptor enkephalinase inhibitors. Furthermore, the TyG index and AIP of the patients 12 months after DAPA administration at discharge were significantly lower than those during hospitalization. Conclusions: DAPA is an independent protective factor against MACE and may provide incremental prognostic information in patients with AMI undergoing PCI. [ABSTRACT FROM AUTHOR]

In this paper, a fast finite volume method is proposed for the initial and boundary value problems of spatial fractional diffusion equations on nonuniform meshes. The discretizations of the Riemann-Liouville fractional derivatives lead to unstructured dense coefficient matrices, differing from the Toeplitz-like structure under the uniform mesh. The fast algorithm is proposed by using the sum-of-exponentials (SOE) technique to the spatial kernel x α − 1 , α ∈ (0 , 1). Then, the matrix-vector multiplications of the resulting coefficient matrices could be implemented in O (m log 2 ⁡ m) operations, where m denotes the size of matrices. Iterative solvers are preferably applied to obtain the numerical solution. The proposed fast scheme is proved to be unconditionally stable for sufficiently accurate SOE approximation. Meanwhile, a banded preconditioner is exploited to accelerate the Krylov subspace method. Numerical experiments are provided to demonstrate the efficiency of the proposed fast algorithm. [ABSTRACT FROM AUTHOR]

A family of new TbIII and 3d–TbIII cluster complexes, namely [Tb(L)(CH3COCH3)] (1), [Tb2(μ-H2O)(L)2] (2), [Zn2Tb(L)2]·ClO4 (3) and [Ni2Tb(L)2]·ClO4 (4) (H3L = N,N′,N′′-tris(3,5-dimethyl-2-hydroxybenzyl)-1,4,7-triazacyclononane), have been synthesized through the reaction of H3L and metal salts. Structural analysis reveals that 1 and 2 exhibit mononuclear and binuclear structures, respectively, and both 3 and 4 exhibit trinuclear 3d–4f–3d structures. Interestingly, complex 1 could undergo reversible transformation to complex 2 by adjusting the reaction solvents. The alternating current (ac) magnetic susceptibilities of 3 reveal that out-of-phase (χ′′) is frequency- and temperature-dependent, which is a typical feature of field-induced slow magnetic relaxation with an energy barrier of 35.71 K. Moreover, complexes 1–3 show strong oxygen-sensitive luminescence, with typical narrow emission bands of lanthanide ions. The luminescence intensity and lifetime (5D4 of TbIII) of 3 are obviously stronger than those of 1 and 2. Therefore, complex 3 can be considered as a good candidate as a bi-functional magneto-luminescent molecular material. [ABSTRACT FROM AUTHOR]

Two multifunctional lanthanide complexes, namely [Dy(HL)]·CH3OH (1) and [Er(HL)]·CH3OH (2), [H4L = N,N′,N′′,N′′′‐tetra(3,5‐dimethyl‐2‐Hydroxybenzyl)‐1,4,7,10‐tetraazacyclododecane] were synthesized and structurally characterized. Complexes 1 and 2 are isomorphic and crystallize in the non‐centrosymmetric orthorhombic space group Pca21. Their structure consists of one seven‐coordinated LnIII ion with the coordination geometry of trigonal prism, one HL3– ligand and one lattice methanol molecule. They exhibit second‐harmonic generation (SHG) effect. Complex 1 displays strong fluorescent emissions, which are typical narrow emission bands of lanthanide ions. In addition, complex 1 features field‐induced slow magnetic relaxation behavior. Therefore, complex 1 may be a potential multifunctional molecular material. Two lanthanide (Dy and Er) complexes have been synthesized and the Dy complex may be a potential multifunctional molecular material with field‐induced slow magnetic relaxation, luminescent and SHG properties. [ABSTRACT FROM AUTHOR]

Based on two-band isotropic Ginzburg-Landau theory, we study the temperature dependence of upper critical field and London penetration depth for non-centrosymmetric superconductor LaNiC2. All the theoretical calculations fit the experimental data very well, especially the upward curvature of upper critical field near the critical temperature. Our results thus indicate that the two-gap scenario is better to account for the superconductivity of LaNiC2, and the Cooper pairs of this superconductor are in the conventional s-wave state. [ABSTRACT FROM AUTHOR]

Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait., is a traditional Chinese medicine that has been used for tonifying the kidney and liver for decades. This study aimed to explore and identify polysaccharides from FLL and elucidate its protective effect against renal fibrosis. Polysaccharides were extracted and isolated from FLL. The purified fraction was identified by serial phytochemical work, such as gel-permeation chromatography, ion chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance. Mice with unilateral ureteral obstruction (UUO) were applied as a renal fibrosis model. The male UUO mice were pretreated with heteropolysaccharide (Poly) 1 week prior to surgery and continuously treated for 7 days after the operation. Renal fibrosis was assessed by Periodic Acid-Schiff (PAS) staining and Masson's trichrome staining in paraffin-embedded slides. The murine mesangial cells SV40-MES13 upon angiotensin II (Ang II) treatment were developed as an in vitro fibrotic model. The cells were treated by Poly in the presence of Ang II. Molecular expression was detected by RT-PCR, immunoblotting, and immunofluorescence staining. We identified a heteropolysaccharide composed of arabinose and galactose (molar ratio, 0.73:0.27) with a predicted chemical structure characterized by a backbone composed of 1,5-α-Ara f , 1,3,5-α-Ara f , 1,6-α-Gal p , and 1,3,6-β-Gal p and side chains comprised of T-α-Ara f , T-α-Ara p , and 1,3-α-Ara f. Pretreatment of UUO mice with Poly effectively alleviated glomerulosclerosis and tubulointerstitial fibrosis. Moreover, Poly pretreatment down-regulated the expression of extracellular matrix (ECM) protein fibronectin (FN), profibrotic factor VEGF, proinflammatory cytokines MCP-1 and Rantes in the obstructed kidney. Similarly, the incubation of SV40-MES13 cells with Poly significantly inhibited Ang II-induced elevation in accumulation and expression level of FN and attenuated Ang II-evoked up-regulation in protein expression of MCP-1 and Rantes. Our study isolated and identified a naturally occurring heteropolysaccharide in FLL and revealed its potential in protecting the kidneys from fibrosis. [Display omitted] • A heteropolysaccharide (Poly) was isolated and purified from Fructus Ligustri Lucidi. • The heteropolysaccharide consists of arabinose and galactose (0.73:0.27). • Poly repressed glomerulosclerosis and tubulointerstitial fibrosis of UUO mice. • Poly inhibited Ang II-evoked induction of profibrotic cytokines. [ABSTRACT FROM AUTHOR]

Diabetic vascular calcification in the arterial intima is closely associated with endothelial-to-mesenchymal transition (EndMT). Glucose metabolism reprogramming is involved in EndMT. Although brain-derived neurotrophic factor (BDNF) and Krüppel-like family of transcription factor 2 (KLF2) play protective roles in the physiological activity of the vascular endothelium, the underlying mechanisms are unclear. Human umbilical vein endothelial cells (HUVECs) were incubated with diabetic osteogenic medium (DOM) to induce EndMT and accelerate osteogenic differentiation. Glycolysis in HUVECs was assessed by monitoring glucose uptake, lactate production, extracellular acidification rate and expression of key glycolytic enzymes. DOM induced EndMT and accelerated osteo-induction in HUVECs, which was alleviated by BDNF/tropomyosin receptor kinase B (TrkB) pathway. Mechanistically, DOM caused hyperactivation of glycolysis in HUVECs and inhibition of the BDNF/TrkB pathway. BDNF preserved KLF2 and downregulated hexokinase 1 (HK1) in HUVECs after DOM treatment. Furthermore, KLF2 interacted with HK1. Increased KLF2 alleviated HK1-mediated glucose metabolism abnormality. HK1 knockdown or a targeted glycolysis inhibitor suppressed EndMT, apoptosis, inflammation and vascular calcification of HUVECs after DOM exposure. This study suggests that KLF2 mediates the suppressive effect of BDNF on diabetic intimal calcification by inhibiting HK1-induced glucose metabolism reprogramming and the EndMT process. • BDNF inhibited the EndMT process and alleviated diabetic osteo-induction in HUVECs. • DOM induced glycolysis hyperactivation, which was partly suppressed via the BDNF/TrkB/KLF2 pathway. • HK1 knockdown or glycolysis blockade diminished DOM-induced EndMT and HUVECs calcification. [ABSTRACT FROM AUTHOR]

R4375 --> 698.12 --> Background: A number of preclinical advances have indicated the cellular and molecular mechanisms underlying renal fibrosis, such as the signaling of angiotensin II (Ang II), which is a bioactive peptide in renin‐angiotensin system. As one of kidney‐tonifying herbs, Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait. (Oleaceae) recorded as a tonic and dietary supplement, is a commonly prescribed component in traditional kidney‐tonifying herbal formula. This study aimed to clarify the polysaccharide component in FLL and investigate its potential role in preservation against renal fibrosis. Methods: The crude polysaccharide of FLL was prepared and deproteinized by Sevag reagent. After lyophilization, the DEAE‐cellulose DE52 column and the Sephacryl S‐200 HR column were used for further isolation and purification of homogenous polysaccharide. The mice with unilateral ureteral obstruction (UUO) underwent daily intraperitoneal injection with FLL polysaccharide starting 7 days before UUO surgery until day 7 after surgery. The murine mesangial SV40‐MES13 cells were treated with vehicle, Ang II (10‐7 M) either with the absence and presence of angiotensin type I receptor blocker (ARB) (10‐6M), or with low dose (50 μg/mL, Poly‐L) and high dose (200 μg/mL, Poly‐H) of FLL polysaccharide. Results: The purified homogenous polysaccharide (Poly) was explored from FLL and the carbohydrate content was 97.45%. A hypothetical structure for Poly was proposed considering the comprehensive data of methylation, monosaccharides, and NMR analyses. Treatment of UUO mice with Poly decreased kidney index and ameliorated glomerular sclerosis and interstitial fibrosis, as well as down‐regulated the expression of profibrogenic factor VEGF and matrix fibrotic protein fibronectin (FN). Furthermore, as the same effect to ARB, the pre‐incubation with Poly alleviated the Ang II‐induced up‐regulation of FN in mesangial cells by immunofluoresence staining. The protein expressions of FN and proinflammatory factors like MCP‐1 and Rantes were significantly lower in Poly‐treated cell group than those in Ang II treatment group. Conclusion: The polysaccharide of Ligustrum lucidum Ait. was accurately explored with structure clarification. This polysaccharide component repressed angiotensin II‐induced fibrotic phenotype of renal mesangial cells and exerted beneficial effects on kidney of UUO mice. [ABSTRACT FROM AUTHOR]

Two novel microporous anionic lanthanide metal–organic frameworks (Ln-MOFs), namely {[(CH3)2NH2][Ln(bptc)]·2H2O}n (Ln = Gd (1) and Dy (2), H4bptc = biphenyl-3,3′,5,5′-tetracarboxylic acid) with a new 4,8-connected topology have been synthesized and structurally characterized. Ln-MOF 1 shows a significant magnetocaloric effect with −ΔS maxm = 26.37 J kg−1 K−1 at 2 K for ΔH = 7 T, and a high proton conductivity of 1.02 × 10−4 S cm−1 at 323 K and 90% RH. Moreover, Ln-MOF 1 shows specific selective adsorption of the cationic dye Rhodamine B. Ln-MOF 2 exhibits field-induced slow magnetic relaxation with an energy barrier (Ueff) of 48.19 K, characteristic emission of Dy3+, and selective adsorption of Rhodamine B. Therefore, 2 is a multifunctional Ln-MOF with magnetic, fluorescence and selective adsorption properties. [ABSTRACT FROM AUTHOR]

Abstract: Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has been shown to exhibit anti-angiogenic and anti-tumor effects apart from its antimalarial activity. In this study, we demonstrate that the combined treatment of cisplatin (CDDP) and DHA exerts a strong, synergistic anti-proliferative effect in human lung carcinoma cells, including A549 and A549/DDP cells, with an average combination index below 0.7. Moreover, the in vivo anti-tumor efficacy of CDDP treatment was increased by DHA. The enhanced anti-cancer activities were also accompanied by reduced tumor microvessel density, increased CDDP concentration within A549 and A549/DDP xenograft BALB/c athymic mice models and suppressed expression of the vascularization-related proteins HIF-1α and VEGF both in vivo and in vitro. Furthermore, the level of apoptosis in the tumor cells increased with the combined treatment of DHA and CDDP. Taken together, our results indicate that a combination of DHA and CDDP treatments synergistically affects tumor angiogenesis, and these results provide a clear rationale for the investigation of these drugs in future clinical trials. [Copyright &y& Elsevier]

A simple and effective template-free synthesis method for nanosized conducting polymers with self-stability and functionality is a main challenge. Herein, a strategy is reported for the facile synthesis of poly(1,5-diaminonaphthalene) nanospherical particles by an interfacial miniemulsion oxidative polymerization of 1,5-diaminonaphthalene at mobile microinterfaces between a stirred biphase without external emulsifiers. The size of the nanospheres was carefully optimized by controlling the polymerization conditions. Formation and self-stabilization mechanisms of the nanoparticles are proposed. The constantly movable and refreshed microinterface is a key to successful synthesis of the nanospheres, for significantly suppressing secondary growth leading to agglomerated particles because vigorous stirring makes as-formed self-stabilized nanospheres instantly leave the microinterfaces. The resulting nanospheres possess several advantages: clean surface, self-stability, redispersibility, semiconductivity, electroactivity, and fluorescence emission. The fluorescence emission can be quenched by specific quenchers, thus enabling low-cost, high-performance chemosensors to be obtained for the sensitive detection of ZnII ions in a wide linear concentration range of more than five orders of magnitude with a superior detection limit down to 1 n M. [ABSTRACT FROM AUTHOR]

A family of novel lanthanide-based metal–organic frameworks (Ln-MOFs) with bifunctional fluorescence sensing properties, namely, {[(CH3)2NH2]5[Ln5(TBAPy)5]·solvent}n (Ln = Gd (1), Tb (2), and Dy (3); H4TBAPy = 1,3,5,7-tetra(4-carboxybenzene)pyrene), was synthesized and structurally characterized. Structural analysis reveals that Ln-MOFs1–3 are isomorphic, and Gd-MOF1 has a three-dimensional structure with a porosity of 20.40%. Due to the existence of the pyrene ring featuring a conjugated system, Ln-MOFs1–3 exhibit strong fluorescence emission. Interestingly, Ln-MOFs1–3 could be considered as good bifunctional fluorescence sensors toward acetylacetone and aspartic acid via a turn-on effect. The detection limits of Tb-MOF2 toward acetylacetone and aspartic acid are 0.129 and 0.025 ppm, respectively. Furthermore, the probable sensing mechanisms for target analytes were also discussed in detail. [ABSTRACT FROM AUTHOR]

Two new ZnII–LnIII heterometallic complexes derived from the amine-phenol ligand, namely [Zn2Ln(L)2(H2O)2](ClO4)3·3.5H2O (Ln = Dy (1) and Tb (2), H2L = 1,2-bis(3-methoxysalicylideneethylaminooxy)ethane), have been synthesized and structurally characterized. Complexes 1 and 2 are isomorphic trinuclear clusters and crystallize in the triclinic P1¯ space group. Magnetic measurements indicate that complex 1 exhibits field-induced slow magnetic relaxation with energy barrier of 27.91 K. Both display strong fluorescence emissions, which are typical narrow emission bands of lanthanide ions. Moreover, complex 2 shows a proton conductivity of 6.43 × 10−5 S cm−1 at 60 °C and 98% relative humidity. Complexes 1 and 2 as multifunctional materials may offer a potential application in magnetic, luminescent, and electrical devices. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the leading causes of cancer-related death in men, however, there was only limited effective treatment for invasive bladder cancer. DAPK1 has been shown to play important role in apoptosis and autophagy to suppress cancer progression. Previous results have shown that DAPK1 promoter was hypermethylated in the majority of bladder cancer specimens, however, the prognostic significance of DAPK1 in bladder cancer has yet to be demonstrated. In the present study, we found that DAPK1 expression was negatively associated with tumor stage and a low level expression of DAPK1 in bladder cancer specimens were associated with shorter survival in bladder cancer patients in 3 independent bladder cancer datasets (n = 462). Further investigation showed that FGFR3 knockdown resulted in downregulation of DAPK1 in bladder cancer cell line, suggesting that FGFR3 may be an upstream factor of DAPK1. Further analysis of the 3 independent bladder cancer datasets have identified ACOX1, UPK2, TRAK1, PLEKHG6 and MT1X genes had their expression significantly correlated with that of DAPK1. Knockdown of DAPK1 in bladder cancer T24 cells resulted in downregulation of ACOX1, UPK2 and TRAK1. Interestingly, TRAK1, by itself, was a favorable prognostic marker in the 3 independent bladder cancer datasets. Importantly, by using connectivity mapping with DAPK1-associated gene signature, we found that vemurafenib and trametinib could possibly reverse DAPK1-associated gene signature, suggesting that inhibition of Raf/MEK pathway may be a potential therapeutic approach for bladder cancer. Indeed, treatment of vemurafenib in T24 bladder cancer cells resulted in upregulation of DAPK1 confirming our connectivity mapping, while knockdown of DAPK1 resulted in reduced sensitivity towards inhibition of Braf signaling by vemurafenib. Together, our results suggest that DAPK1 is an important prognostic marker and therapeutic target for bladder cancer and have identified possible therapeutic agents for future testing in bladder cancer models with low DAPK1 expression. [ABSTRACT FROM AUTHOR]

A finite difference scheme is developed for solving the phase field crystal equation with the Dirichlet boundary condition. The second-order stabilized semi-implicit scheme is applied to discretize the time variable. The mass conservation, unique solvability of the semi-discrete scheme are proved. Then, the spatial discretization is attained by the fourth-order compact difference scheme. The unconditional energy stability and convergence analysis of the fully-discrete scheme are presented. In the implementation, a fast sine transform technique is utilized to reduce the computational cost. Several numerical examples are presented to verify the effectiveness of the proposed scheme. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that tumor immunotherapy resistance is influenced by ADAR-mediated RNA editing, but its targets remain unelucidated. Our current study identified the poliovirus receptor (PVR) oncogene, which encodes an immune checkpoint in colorectal cancer (CRC), as a potential target for RNA editing. We performed transcriptome sequencing analysis and experimental validation in two Chinese CRC cohorts. PVR and ADAR expressions significantly increased in CRC tumors and showed positive correlations in both cohorts, coupled with upregulated PVR RNA editing in CRC tumors. Manipulation of ADAR expression by over-expression or knockdown substantially changed PVR expression and RNA editing in HTC116 CRC cells. Luciferase reporter and actinomycin D assays further revealed that RNA editing in PVR 3′-UTR could upregulate PVR RNA expression, probably by increasing the RNA stability. By increasing PVR expression, ADAR-mediate RNA editing might contribute to tumor- and immune-related gene functions and pathways in CRC. Moreover, a signature combining PVR RNA editing and expression showed promising predictive performance in CRC diagnosis in both Chinese CRC cohorts. Our findings thus highlight the importance of ADAR-mediated RNA editing in PVR up-regulation in CRC tumors and provide new insight into the application of PVR RNA editing as a novel diagnostic biomarker for CRC. • Immune checkpoint PVR was identified as a novel target of ADAR-mediated RNA editing in two Chinese CRC cohorts. • Elevated ADAR expression significantly upregulated PVR RNA editing and expression in CRC. • RNA editing in the PVR 3′-UTR significantly increased the RNA expression, probably by increasing RNA stability. • A signature combining PVR RNA editing and expression showed promising performance in CRC diagnosis in both Chinese cohorts. [ABSTRACT FROM AUTHOR]

Angiosarcomas account for a mere 2-3% of adult soft tissue sarcomas, with an overall poor outcome. Depending on the primary site, angiosarcomas have distinct prognosis. Primary hepatic angiosarcomas ( PHAs) are much rare tumors, with worse prognosis compared with other angiosarcomas. PHA is reported to be associated with vinyl chloride, but the majority of patients were still with unknown etiology. As PHA lacks specific symptoms, signs, or images, pathological diagnosis is necessary. The review summarizes 25 articles published from January 2000 to December 2012, including 64 cases of PHA with detailed information. Survival curves are estimated using the Kaplan- Meier method by SPSS 21.0. We find that the median survival time is 5 months; local excision alone or combination with adjuvant therapy is the optimal choice, with median survival time of 17 months. In addition, liver transplant is abandoned for high recurrence rate; emergent transcatheter arterial embolization is thought to be an efficient method for controlling intra-abdominal bleeding; and transcatheter arterial chemoembolization and chemotherapy may be helpful in improving survival. [ABSTRACT FROM AUTHOR]

Nuclear factor-kappa B (NF-κB) and autophagy are two major regulators involved in both tumor initiation and progression. However, the association between these two signaling pathways still remains obscure. In this work, we demonstrate that dihydroartemisinin (DHA) stimulates the induction of autophagy in several cancer cell lines through repression of NF-κB activity. We also show that inhibiting NF-κB results in an accumulation of reactive oxygen species (ROS), which participate in the stimulation of autophagy. These findings present a pathway by which DHA promotes autophagy in cancer cells and provide evidence for the DHA-induced sensitization effect of some chemotherapeutics. [ABSTRACT FROM AUTHOR]

Highlights: [•] We show that DHA induces autophagy in several cancer cell lines by repressing NF-κB. [•] We verify that inhibiting NF-κB leads to an reduction of FHC and MnSOD expression. [•] Accumulation of ROS participate in the stimulation of autophagy process. [•] Inhibiting NF-κB may contribute to DHA-induced sensitization effect of some agents. [ABSTRACT FROM AUTHOR]

Abstract: The effect of a commercial lipase on chitosan degradation was investigated. When four chitosans with various degrees of deacetylation were used as substrates, the lipase showed higher optimal pH toward chitosan with higher DD (degree of deacetylation). The optimal temperature of the lipase was 55°C for all chitosans. The enzyme exhibited higher activity to chitosans which were 82.8% and 73.2% deacetylated. Kinetics experiments show that chitosans with DD of 82.8% and 73.2% which resulted in lower K m values had stronger affinity for the lipase. The chitosan hydrolysis carried out at 37°C produced larger quantity of COS (chitooligosaccharides) than that at 55°C when the reaction time was longer than 6h, and COS yield of 24h hydrolysis at 37°C was 93.8%. Products analysis results demonstrate that the enzyme produced glucosamine and chitooligosaccharides with DP (degree of polymerization) of 2–6 and above, and it acted on chitosan in both exo- and endo-hydrolytic manner. [Copyright &y& Elsevier]

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP), in which exon open reading frame 15 (ORF15) of RPGR has been implicated to play a substantial role. We identified a novel hemizygous missense mutation E585K of RPGR from whole-exome sequencing of RP. RNA-Seq analysis and functional study were conducted to investigate the underlying pathogenic mechanism of the mutation. Our results showed that the mutation actually affected RPGR ORF15 splicing. RNA-Seq analysis of the human retina followed by validation in cells revealed a complex splicing pattern near the 3′ boundary of RPGR exon 14 in the ORF15 region, resulting from a variety of alternative splicing events (ASEs). The wildtype RPGR mini-gene expressed in human 293T cells confirmed these ASEs in vitro. In contrast, without new RNA species detected, the mutant mini-gene disrupted the splicing pattern of the ORF15 region, and caused loss of RPGR transcript heterogeneity. The RNA species derived from the mutant mini-gene were predominated by a minor out-of-frame transcript that was also observed in wildtype RPGR, resulting from an upstream alternative 5′ splice site in exon 14. Our findings therefore provide insights into the influence of RPGR exonic mutations on alternative splicing of the ORF15 region, and the underlying molecular mechanism of RP. Image 1 • A novel E585K missense mutation was identified in RPGR exon ORF15 from RP. • Retina RNA-Seq revealed a complex splicing pattern near the mutation location. • The mutant affected ORF15 splicing and caused loss of its transcript heterogeneity. • Mutant RNAs were predominated by an out-of-frame minor form observed in wildtype. [ABSTRACT FROM AUTHOR]

A copper-catalyzed decarboxylative/dehydrogenative cross-coupling reaction of α-fluoroacrylic acids with silanes has been developed. A wide range of α-fluoroacrylic acids containing many critical functional groups reacted smoothly, giving desired monofluoroalkenyl silanes with excellent E -stereoselectivity. This protocol provides a convenient strategy for accessing monofluoroalkenyl silanes, without using expensive iridium catalysts to prepare the silylborane and without the need for harsh conditions. [Display omitted] [ABSTRACT FROM AUTHOR]

Stimuli-responsive polymeric hydrogels based on host-guest interactions have demonstrated potential as smart drug delivery platforms. However, host-guest interactions alone have been repeatedly highlighted to provide insufficient mechanical strength for the formed hydrogels likely due to the generally low grafting degrees of functional groups and steric hindrance of polymer backbone and grafted functions. Herein, a combination strategy of reversible addition-fragmentation chain-transfer polymerization (RAFT) and dual crosslinking was employed to fabricate thermo- and pH-dual responsive hydrogels with enhanced mechanical properties. Specifically, two kinds of poly (N -isopropyl acrylamide) (PNIPAM)-based well-defined thermo-sensitive polymers, denoted as P H and P G , consisting of β-cyclodextrin (β-CD) and adamantane (Ad) groups were synthesized via RAFT copolymerization. A facile mixing of P H and P G with commercially available adipic dihydrazide led to the construction of hydrogels via host-guest interactions and dynamic acylhydrazone bonding. The resulting hydrogels not only exhibited pH-switchable sol-gel transitions and temperature-dependent swelling behaviors, but also possessed good stretchability (fracture stress up to 39.97 kPa) and self-healing property (self-healing efficiency above 90%). Notably, the resulting hydrogels showed pH-responsive controlled spatiotemporal release administration of rhodamine B due to the presence of dynamic acylhydrazone links. Together with good cytocompatibility, the hydrogels developed herein represent promising candidates for potential transdermal drug delivery. Both physical and chemical crosslinking strategies, i.e. , host-guest interactions and dynamic acylhydrazone bonding were used to prepare thermo and pH-dual responsive hydrogels with good mechanical strength and self-healing properties for pH-dependent drug release based on two RAFT-synthesized PNIPAM-based thermosensitive copolymers. [Display omitted] • "One-pot" RAFT and dual crosslinking were combined for hydrogel construction. • Dual crosslinking involves host-guest interactions and acylhydrazone bonding. • The hydrogels showed enhanced mechanical strength and self-healing abilities. • The drug-loaded hydrogels possessed pH-dependent drug release behaviors. [ABSTRACT FROM AUTHOR]

Autoantibodies have been widely used as markers of latent autoimmune diabetes in adults (LADA); however, the specificity and sensitivity of autoantibodies as markers of LADA are weak compared with those found in type 1 diabetes (T1DM). In this study, we aimed to identify other plasma proteins as potential candidates that can be used effectively to determine early stage LADA and type 2 diabetes (T2DM) to facilitate early diagnosis and treatment. These issues were addressed by studying new-onset ‘classic’ T1DM (n = 156), LADA (n = 174), T2DM (n = 195) and healthy cohorts (n = 166). Plasma samples were obtained from the four cohorts. We employed isobaric tag for relative and absolute quantitation (iTRAQ) together with liquid chromatography tandem mass spectrometry (LC-MS) to identify plasma proteins with significant changes in LADA. The changes were validated by Western blot and ELISA analyses. Among the four cohorts, 311 unique proteins were identified in three iTRAQ runs, with 157 present across the three data sets. Among them, 49/311 (16.0%) proteins had significant changes in LADA compared with normal controls, including glycoprotein phospholipase D (GPLD1), which was upregulated in LADA. Western blot and ELISA analyses showed that GPLD1 levels were higher in both LADA and T1DM cohorts than in both T2DM and healthy cohorts, while there were no significant differences in the plasma concentrations of GPLD1 between the LADA and T1DM cohorts. GPLD1 is implicated as a potential candidate plasma protein for determining early stage LADA and T2DM. [ABSTRACT FROM AUTHOR]

Besifloxacin is a fourth-generation broad-spectrum fluoroquinolone registered for the topical treatment of bacterial conjunctivitis. In this study, a rapid, sensitive and selective liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed for quantification of besifloxacin in rabbit plasma and ocular tissues using nateglinide as the internal standard (IS). The analyte and IS were separated on a Sepax GP-Phenyl column by isocratic elution with methanol–acetonitrile-5 mM ammonium formate–formic acid (29:55:16:0.1, v/v/v/v) as the mobile phase at a flow rate of 1.2 mL/min, and the total run time was 3.0 min. An electrospray ionization (ESI) source was applied and operated in the positive ion mode; multiple reaction monitoring (MRM) mode was used for quantification, and the monitored transitions were 394.2 → 377.1 for besifloxacin and m / z 318.3 → 166.1 for the IS. The calibration curve was linear over the range of 0.103–206 ng/mL for plasma and 2.06–2060 ng/mL for tears, aqueous humor, conjunctiva and cornea with correlation coefficient ( r ) greater than 0.99. The lower limit of quantification (LLOQ) for besifloxacin was 0.103 ng/mL for plasma and 2.06 ng/mL for other ocular tissues with good accuracy and precision. Intra- and inter-batch precision were both lower than 15% and accuracy ranged from 85% to 115% at all QC levels. The method was successfully applied to the pharmacokinetic study of besifloxacin in rabbit plasma and ocular tissues after single and multiple topical administrations. [ABSTRACT FROM AUTHOR]

• Two-dimensional distributed-order time-space fractional diffusion problem is considered and its finite difference discretization is studied. • The stability and convergence of the scheme are investigated. • The spatial second-order convergence and the temporal optimal convergence are obtained. • A fast and memory saving algorithm for solving DO time-space fractional diffusion equation is developed through Gauss quadrature formula, ESA method and PCG method. • Numerical experiments show strong effectiveness and efficiency of the method. In this paper, a fast algorithm is proposed for solving distributed-order time-space fractional diffusion equations. Integral terms in time and space directions are discretized by the Gauss-Legendre quadrature formula. The Caputo fractional derivatives are approximated by the exponential-sum-approximation method, and the finite difference method is applied for spatial approximation. The coefficient matrix of the discretized linear system is symmetric positive definite and possesses block-Toeplitz-Toeplitz-block structure. The preconditioned conjugate gradient method with a block-circulant-circulant-block preconditioner is employed to solve the linear system. Theoretically, the stability and convergence of the proposed scheme are discussed. Numerical experiments are carried out to demonstrate the effectiveness of the scheme. [ABSTRACT FROM AUTHOR]

Based on quantum information splitting and reconstruction, we present a quantum private comparison (QPC) protocol, enabling two distrustful parties (Alice and Bob) to compare the equality of their information without revealing the information content. In this protocol, the information carriers are split into two wave packets by a beam splitter (BS), which is owned by a semi-honest third party Trent, and then they are sent to Alice and Bob, respectively. Alice and Bob encodes their secret information on the received wave packets. Only the superimposition of the two wave packets in Trent's site can reveal the compared result. Compared with the QPC protocols using entangled states, the information carriers used in our protocol is single-photon pulse, which reduces the difficulty of realization in practical. In addition, our protocol is feasible with the present techniques since only linear optical components, BS, single-photon detector, phase shifter (PS) and switcher (SWT) are required. The security of the protocol is ensured by principles on the phenomenon of quantum interference. And through the security analysis it shows that the protocol is secure and resists against the well-known attacks. [ABSTRACT FROM AUTHOR]

Purpose: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has exhibited the strongest antimalarial activity among the derivatives of artemisinin. There is growing evidence that DHA has some impact against tumors. Our purpose was to evaluate in vitro antitumoral properties of DHA in the murine Lewis lung carcinoma (LLC) cell line. At the same time, we observed the therapeutic effect of DHA combined with cyclophosphamide (CTX) in the LLC and combined with cisplatin (CDDP) in the human non-small cell lung cancer A549 xenotransplanted carcinoma in vivo.Methods: Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, apoptosis was measured by AO/EB double staining and flow cytometry. The expression of vascular endothelial growth factor (VEGF) receptor KDR/flk-1 was analyzed by western blotting and RT-PCR. In vivo activity of DHA combined with CTX or CDDP was assayed through tumor growth and metastasis.Results: Dihydroartemisinin exhibited high anti-cancer activity in LLC cell line. DHA also induced apoptosis of LLC cells and influenced the expression of VEGF receptor KDR/flk-1. Furthermore, in both tumor xenografts, a greater degree of growth inhibition was achieved when DHA and chemotherapeutics were used in combination. The affection by DHA combined CTX on LLC tumor metastasis was significant.Conclusions: Dihydroartemisinin is a potent compound against LLC cell line in vitro. In vivo, the combination strategy of DHA and chemotherapeutics holds promise for the treatment of relatively large and rapidly growing lung cancers. [ABSTRACT FROM AUTHOR]

• Protein modification significantly decreased the allergenic reactivity of α-Lactalbumin. • The type, number and location of the modified sites affected allergenic reactivity. • Shielding effect and conformational changes reduced allergenic reactivity of α-Lactalbumin. Bovine α-lactalbumin (α-Lac) allergy is a common health problem. This study assesses the allergenic reactivity and the structural properties of α-Lac after protein modification (glycation, phosphorylation and acetylation) by ELISA, cells experiment and high-resolution mass spectrometry. Three modified methods significantly reduced the IgE/IgG-binding capacity, and the release of histamine and interleukin-6, and changed the conformational structure of α-Lac. α-Lac was glycated at K13, K16, K94, K98, and K108, phosphorylated at Y18, S22, Y103, and S112, and acetylated at K13, T33, S34, T38, S47, K62, S69, S70, K108, and K114, respectively, leading to masking the linear epitopes of α-Lac. Therefore, the decrease of allergenic reactivity of α-Lac induced by glycation, phosphorylation and acetylation depends upon not only the shielding effect of their modified sites, but also the change of conformational structure. This study confirmed that protein modification was a promising method for decreasing the allergenic reactivity of allergic proteins. [ABSTRACT FROM AUTHOR]

Background: Partial epithelial mesenchymal transition (p-EMT) was found to play a potential role in the initial stage of metastasis in human head and neck squamous cell carcinoma (HNSCC). Some long noncoding RNAs (lncRNAs) have been reported to function as promoters or inhibitors of cancer metastasis. This study aimed to identify p-EMT-related lncRNAs in HNSCC. Methods: Differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DEGs) in HNSCC obtained from The Cancer Genome Atlas (TCGA) were screened out by using the "edgeR" package. DE-lncRNAs in the Oral squamous cell carcinoma (OSCC) lncRNA microarray dataset GSE84805 were screened out by using the "limma" package. Slug-related lncRNAs were determined by Pearson correlation analysis (|Pearson correlation coefficient| ≥ 0.4, p < 0.01) based on TCGA. Survival analysis were performed for the overlapping DE-lncRNAs by using the "Survival" package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict the potential functions of MYOSLID. RT-qPCR and In Site Hybridization (ISH) were used to explore the MYOSLID expression and its clinical significance in HNSCC specimens. Immunohistochemical staining, siRNA, wound healing assay, transwell assay, and western blot were used to explore the biological function and potential molecular mechanisms. Results: MYOSLID was identified as a Slug-related lncRNA and with prognostic value among the 9 overlapping DE-lncRNAs. GO and KEGG analyses revealed that MYOSLID was closely related to important biological processes and pathways that regulate cancer metastasis. The results of univariate and multivariate Cox regression analysis based on TCGA and HNSCC tissue microarray data suggested MYOSLID was an independent prognostic factor. MYOSLID expression in HNSCC was closely correlated with Slug, PDPN and LAMB3. The knockdown of MYOSLID in OSCC cell line significantly inhibited cell migration and invasion compared to those in the control cells. In addition, the knockdown of MYOSLID significantly reduced Slug, PDPN and LAMB3 expression levels. However, the knockdown of MYOSLID had no effect on the expression levels of the EMT biomarkers E-cadherin and Vimentin. Conclusions: Our study revealed that MYOSLID expression was closely related to the p-EMT program in HNSCC, and it might be a new predictive biomarker for aggressive HNSCC. [ABSTRACT FROM AUTHOR]