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Abstract Imbalance of proinflammatory and anti-inflammatory responses plays a crucial role in the progression of abdominal aortic aneurysms. ILF3, a known modulator of the innate immune response, is involved in cardiovascular diseases. This study aims to investigate the role of ILF3 in abdominal aortic aneurysm formation. Here, we use multi-omics analyzes, transgenic male mice, and multiplex immunohistochemistry to unravel the underlying involvement of ILF3 in abdominal aortic aneurysms. The results show that macrophage ILF3 deficiency attenuates abdominal aortic aneurysm progression, while elevated macrophage ILF3 exacerbates abdominal aortic aneurysm lesions. Mechanistically, we reveal that macrophagic ILF3 increases NF-κB activity by hastening the decay of p105 mRNA, leading to amplified inflammation in macrophages. Meanwhile, ILF3 represses the anti-inflammatory action by inhibiting the Keap1-Nrf2 signaling pathway through facilitating the ILF3/eIF4A1 complex-mediated enhancement of Keap1 translational efficiency. Moreover, Bardoxolone Methyl treatment alleviates the severity of abdominal aortic aneurysm lesions in the context of elevated ILF3 expression. Together, our findings underscore the significance of macrophage ILF3 in abdominal aortic aneurysm development and suggest its potential as a promising therapeutic target for abdominal aortic aneurysms.

Abstract Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products (AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.

Recently, the construction of the trisubstituted olefin-type probe molecules has elicited the attention of many researchers. However, the synthesis of the trisubstituted olefin-type probes containing two N-heterocycles simultaneously has been rarely reported. In this study, starting from the inexpensive mucobromic acid 1 and N-heterocyclic compound 2, we first utilized a simple one-step reaction to synthesize a series of trisubstituted olefin-type compounds 3 simultaneously bearing with the structure of two N-heterocyclic rings in the absence of transition metal catalysts with a yield of 62–86%. The optimal reaction conditions were systematically explored, and the structure of the obtained compounds 3 were well characterized with 1H NMR, 13C NMR, X-ray single-crystal and HR-MS. The preliminary observation showed that, in the presence of base, mucobromic acid 1 reacts as its ring-opening structure, and the successive nucleophilic substitution reaction and Michael addition reaction can generate the target product 3. Considering that the aldehyde group in the molecular structure of the trisubstituted olefin-type compounds 3 may react with malononitrile, we carried out some relevant investigations so as to realize the visual detection of malononitrile. Interestingly, among the products, compounds 3a–3c can be prepared in portable test strips through a simple process and used to achieve the naked-eye detection of malononitrile in environmental systems as designed.

Summary: Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10−6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

Abstract Hypergolic propellants rely on fuel and oxidizer that spontaneously ignite upon contact, which fulfill a wide variety of mission roles in launch vehicles and spacecraft. Energy‐rich carboranes are promising hypergolic fuels, but triggering their energy release is quite difficult because of their ultrastable aromatic cage structure. To steer the development of carborane‐based high‐performance hypergolic material, carboranylthiolated compounds integrated with atomically precise copper clusters are presented, yielding two distinct isomers, Cu14B‐S and Cu14C‐S, both possessing similar ligands and core structures. With the migration of thiolate groups from carbon atoms to boron atoms, the ignition delay (ID) time shortened from 6870 to 3 ms when contacted with environmentally benign oxidizer high‐test peroxide (HTP, with a H2O2 concentration of 90%). The extraordinarily short ignition ID time of Cu14B‐S is ranking among the best of HTP‐active hypergolic materials. The experimental and theoretical findings reveal that benefitting from the migration of thiolate groups, Cu14B‐S, characterized by an electron‐rich metal kernel, displays enhanced reducibility and superior charge transfer efficiency. This results in exceptional activation rates with HTP, consequently inducing carborane combustion and the simultaneous release of energy. This fundamental investigation shed light on the development of advanced green hypergolic propulsion systems.

As an important class of nitrogen-containing fused heterocyclic compounds, imidazo[1,2-a]pyridines often exhibit significant biological activities, such as analgesic, anticancer, antiosteoporosis, anxiolytic, etc. Using Y(OTf)3 as a Lewis acid catalyst, a simple and efficient method has been developed for the synthesis of C3-alkylated imidazo[1,2-a]pyridines through the three-component aza-Friedel–Crafts reaction of imidazo[1,2-a]pyridines, aldehydes, and amines in the normal air atmosphere without the protection of inert gas and special requirements for anhydrous and anaerobic conditions. A series of imidazo[1,2-a]pyridine derivatives were obtained with moderate to good yields, and their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Furthermore, this conversion has the advantages of simple operation, excellent functional group tolerance, high atomic economy, broad substrate scope, and can achieve gram-level reactions. Notably, this methodology may be conveniently applied to the further design and rapid synthesis of potential biologically active imidazo[1,2-a]pyridines with multifunctional groups.

An efficient and operationally simple method for the synthesis of β-keto sulfones through the BF3·OEt2-promoted reaction of alkynes and sodium sulfinates is developed. With its facile and selective access to the targets, it features good functional group compatibility, mild conditions, easily available starting materials, and good yields. Notably, the reaction does not require metal catalysts or chemical reagents with pungent odors.

Abstract Chiral metal‐organic frameworks (MOFs) are usually endowed by chiral linkers and/or guests. The strategy using chiral secondary building units in MOFs for solving the trade‐off of circularly polarized luminescence (CPL)‐active materials, high photoluminescence quantum yields (PLQYs) and high dissymmetry factors (|glum|) has not been demonstrated. This work directionally assembles predesigned chiral silver clusters with ACQ linkers through reticular chemistry. The nanoscale chirality of the cluster transmits through MOF's framework, where the linkers are arranged in a quasi‐parallel manner and are efficiently isolated and rigidified. Consequently, this backbone of chiral cluster‐based MOFs demonstrates superb CPL, high PLQYs of 50.3%, and |glum| of 1.2 × 10−2. Crystallographic analyses and DFT calculations show the quasi‐parallel arrangement manners of emitting linkers leading to a large angle between the electric and magnetic transition dipole moments, boosting CPL response. As compared, an ion‐pair‐direct assembly without interactions between linkers induces one‐ninth |glum| and one‐sixth PLQY values, further highlighting the merits of directional arrangement in reticular nets. In addition, a prototype CPL switching fabricated by a chiral framework is controlled through alternating ultraviolet and visible light. This work is expected to inspire the development of reticular chemistry for high‐performance chiroptical materials.

Abstract Background As cancer is one of the main leading causes of mortality, a series of monotherapies such as chemotherapy, gene therapy and radiotherapy have been developed to overcome this thorny problem. However, a single treatment approach could not achieve satisfactory effect in many experimental explorations. Results In this study, we report the fabrication of cyclic RGD peptide (cRGD) modified Au4-iron oxide nanoparticle (Au4-IO NP-cRGD) based on aggregation-induced emission (AIE) as a multifunctional theranostic system. Besides Au4 cluster-based fluorescence imaging and enhanced radiotherapy, iron oxide (IO) nanocluster could realize magnetic resonance (MR) imaging and Fenton reaction-based chemotherapy. Abundant toxic reactive oxygen species generated from X-ray irradiation and in situ tumor-specific Fenton reaction under acidic microenvironment leads to the apoptotic and necrotic death of cancer cells. In vivo studies demonstrated good biocompatibility of Au4-IO NP-cRGD and a high tumor suppression rate of 81.1% in the synergistic therapy group. Conclusions The successful dual-modal imaging and combined tumor therapy demonstrated AIE as a promising strategy for constructing multifunctional cancer theranostic platform. Graphical Abstract

Organic thioethers play an important role in the discovery of drugs and natural products. However, the green synthesis of organic sulfide compounds remains a challenging task. The convenient and efficient synthesis of 5-alkoxy-3-halo-4-methylthio-2(5H)-furanones from DMSO is performed via the mediation of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), affording a facile route for the sulfur-functionalization of 3,4-dihalo-2(5H)-furanones under transition metal-free conditions. This new approach has demonstrated the functionalization of non-aromatic Csp2-X-type halides with unique structures containing C-X, C-O, C=O and C=C bonds. Compared with traditional synthesis methods using transition metal catalysts with ligands, this reaction has many advantages, such as the lower temperature, the shorter reaction time, the wide substrate range and good functional group tolerance. Notably, DMSO plays multiple roles, and is simultaneously used as an odorless methylthiolating reagent and safe solvent.

AIM: To evaluate the safety and efficacy of limbal conjunctival autograft transplantation for treating primary pterygium over a period of 3y.METHODS: Prospective observational consecutive case series. In this study, 264 eyes of 264 patients(142 males and 122 females)with nasal primary pterygium were treated using the technique of limbal conjunctival autograft. The mean ages of the patients were 54.22±15.24a. After excision of the pterygium patients were followed up on 1, 3, 7d and at 1, 3, 6, 9, 12 and 36mo. Recurrence of pterygium, complications, operation time and corneal epithelialization time were evaluated.RESULTS: The average surgery time was 25.7±2.6min. With a minimum 3-year of follow-up, postoperative corneal epithelialization was completed in 3.85±0.72d. Complications were observed in 14 cases. Vision-threating complications such as iritis, scleral thinning symblepharon or ulceration were not detected in the study. 5 eyes with graft edema, 3 eyes with granuloma formation and 6 cases with a subconjunctival hematoma in the nasal conjunctiva. By the end of 3-year follow-up, recurrence was detected in 11 cases. The recurrence rate was 4.17%, and the onset of recurrence was 3mo, the average recurrence time was 8mo.CONCLUSION: There were no severe complications and few recurrences when limbal conjunctival autograft transplantation was performed after long-term follow-up, we suggest that limbal conjunctival autograft transplantation is a safe and effective technique in primary pterygium. We also recommend that 12-month follow-up is optimal on primary pterygium surgery.

Incorporating dual fluorescence and phosphorescence into a single matrix is attractive for oxygen sensing, but material design is challenging. Here the authors achieve dual fluorescence-phosphorescence from a single linker chromophore in a silver chalcogenolate-cluster-based metal-organic framework.

"AIM: To explore the traumatic endophthalmitis in young children and the outcome of pars plana vitrectomy (PPV). METHODS: Twenty-two eyes of 22 cases of young children consecutive pediatric traumatic endophthalmitis treated and followed up between September 2014 and May 2018 were included. Aqueous humor or vitreous samples were taken for bacterial culture and sensitivity tests. Intravitreal antibiotics (norvancomycin and ceftazidime) injection, combined with 23-gauge PPV, were administered in 22 eyes. Silicone oil (SO; 5000 centistoke) tamponade or perfluoropropane gas (C3F8) was used in all patients. Main outcome measures were best-corrected visual acuity (BCVA) and retinal attachment, the ratio of penetrating injury, and the existence of intraocular foreign body. RESULTS: The mean age of patients was 6.9±2.2 (range, 3-10)y. All injured eyes suffered from penetrating ocular injury with retained intraocular foreign body in one eye. Bacterial culture was positive in only 2 eyes. The mean follow-up time was 21.1±4.7 (range, 12-30)mo. In the primary PPV, intravitreal antibiotics was administrated in all eyes, SO in 18 eyes, and C3F8 in 4 eyes. The secondary operation of SO removal and C3F8 endotamponade was performed in 16 eyes and a second SO endotamponade due to emulsification of the oil and retinal detachment (RD) was operated in 7 eyes underwent 3 to 11.5mo after primary PPV. A third operation was done in 7 eyes. The final intraocular pressure (IOP) was 8.9±1.8 (range, 6.9-11.4) mm Hg. The final BCVAs were 20/200 or better in 5, counting fingers in 2, and light perception to hand movement in 8 eyes. Whose (66.7%) had retinal injury exhibited worse BCVA (P=0.019, Fisher’s exact test). Eyes underwent SO tamponade exhibited worse final BCVA than that with C3F8 in the primary PPV (P=0.026, Fisher’s exact test). CONCLUSION: Traumatic endophthalmitis in children is generally more severe and associated with more complicated surgical procedures. Most patients have retinal injury need multiple operations and the final BCVA is poor. Prevention of ocular trauma, especially in children, is still critical."

Objective. To explore the features and diagnostic value of computed tomography (CT) imaging in cases of thymic cysts. Methods. A total of 24 cases of the thymic cysts (confirmed by postoperative pathology) were retrospectively analyzed. The location, morphology, and density of the thymic cysts were summarized, and the changes in CT value of the region of interest (ROI) in the thymic cysts between noncontrast enhanced and enhanced chest scans were compared and classified. Results. The average long-axis dimension was 17.50 ± 6.00 mm, the CT value range across the 24 cases was 5–81 HU, and the average CT value of the noncontrast enhanced scans was 39.75 ± 20.66 HU. The CT value in the noncontrast enhanced scan was >20 HU in 79% of the sample cases. The CT value in the ROI of the thymic cysts under enhanced scan showed a significant decrease in 15 cases, a significant increase in 5 cases, and an insignificant change in 4 cases. Conclusion. The CT values of the thymic cysts in the enhanced scans were generally lower than in the noncontrast enhanced scans, which might be a valuable finding for thymic cysts diagnosis.

Abstract Background To report a modified surgical technique for intrascleral intraocular lens (IOL) fixation with fewer anterior segment manipulations in eyes lacking sufficient capsular support. Methods Eyes from 14 patients who underwent 27-gauge needle-guided intrascleral IOL fixation with built-in 8–0 absorbable sutures were studied. The 8–0 absorbable sutures were inserted into 27-gauge round needles and used to create sclerotomies at the 4 o’clock and 10 o’clock positions under the scleral flap. The sutures were used to tie knots at the end of each haptic and guide haptic externalization through the sclerotomy. After externalization, a sufficient flange was created at the end of each haptic and fixed under the scleral flaps. The best corrected visual acuity (BCVA), corneal endothelial cell density (ECD), IOL tilt and decentration, previous surgery history, and complications were determined. Results Fourteen cases were analyzed. The majority of eyes exhibited an improvement in the BCVA after surgery. When comparing the last follow-up to preoperative visual acuity, the mean change in BCVA was + 26.32 letters (p = 0.011). Postoperative complications included postoperative hypotony in 3 eyes, ocular hypertension in 2 eyes. No cases of postoperative cystoid macular edema (CME), vitreous hemorrhage (VH), IOL dislocation, or endophthalmitis were observed. Conclusions The 27-gauge needle-guided intrascleral IOL fixation technique with built-in 8–0 absorbable sutures is easy to perform with fewer anterior chamber manipulations and achieves both anatomical and optical stability.

Diabetes mellitus (DM) promotes neointimal hyperplasia, characterized by dysregulated proliferation and accumulation of vascular smooth muscle cells (VSMCs), leading to occlusive disorders, such as atherosclerosis and stenosis. Poly (ADP-ribose) polymerase 1 (PARP1), reported as a crucial mediator in tumor proliferation and transformation, has a pivotal role in DM. Nonetheless, the function and potential mechanism of PARP1 in diabetic neointimal hyperplasia remain unclear. In this study, we constructed PARP1 conventional knockout (PARP1−/−) mice, and ligation of the left common carotid artery was performed to induce neointimal hyperplasia in Type I diabetes mellitus (T1DM) mouse models. PARP1 expression in the aorta arteries of T1DM mice increased significantly and genetic deletion of PARP1 showed an inhibitory effect on the neointimal hyperplasia. Furthermore, our results revealed that PARP1 enhanced diabetic neointimal hyperplasia via downregulating tissue factor pathway inhibitor (TFPI2), a suppressor of vascular smooth muscle cell proliferation and migration, in which PARP1 acts as a negative transcription factor augmenting TFPI2 promoter DNA methylation. In conclusion, these results suggested that PARP1 accelerates the process of hyperglycemia-induced neointimal hyperplasia via promoting VSMCs proliferation and migration in a TFPI2 dependent manner.

Summary: A series of N-alkyl-substituted polybenzimidazoles (SPBIs), synthesized by simple condensation and N-alkylation, act as functional materials with tunable microstructures and sensing performance. For their controllable morphologies, the formation of nano-/microspheres is observed at the n(RBr)/n(PBI) feed ratio of 5:1. Products with different degrees of alkylation can recognize metal ions and nitroaromatic compounds (NACs). For example, SPBI-c, obtained at the feed ratio of 1:1, can selectively detect Cu2+, Fe3+, and NACs. By contrast, SPBI-a, obtained at the feed ratio of 0.1:1, can exclusively detect Cu2+ with high sensitivity. Their sensing mechanisms have been studied by FT-IR spectroscopy, SEM, XPS, and DFT calculations. Interestingly, the SPBIs can adsorb Cu2+ in solution and show good recyclability. These results demonstrate that polymeric materials with both sensing and adsorption applications can be realized by regulating the alkylation extent of the main chain, thus providing a new approach for the facile synthesis of multifunctional materials.

Summary: The bio-based lactic acid (LA) and the common metal ion chelating agent iminodiacetic acid (IDA) are used to design and prepare a polymeric sustained-release Pb2+ chelating agent by a brief one-step reaction. After the analysis on theoretical calculation for this reaction, poly(lactic acid-iminodiacetic acid) [P(LA-co-IDA)] with different monomer molar feed ratios is synthesized via direct melt polycondensation. P(LA-co-IDA) mainly has star-shaped structure, and some of them have two-core or three-core structure. Thus, a possible mechanism of the polymerization is proposed. The degradation rate of P(LA-co-IDA)s can reach 70% in 4 weeks. The change of IDA release rate is consistent with the trend of the degradation rate, and the good Pb2+ chelating performance is confirmed. P(LA-co-IDA) is expected to be developed as a lead poisoning treatment drug or Pb2+ adsorbent in the environment with long-lasting effect, and this research provides a new strategy for the development of such drugs.

AIM: To measure and analysis axial length (AL)/corneal radius of curvature (CRC) ratio and other refractive parameters, provide a medical reference range for refractive development evaluation and earlier visual impairment screening of 3 to 4y kindergarten students. METHODS: Between April and June 2017, a total of 4350 participants aged 3- to 4-year-old (8700 eyes) from 10 cluster random sampling kindergartens in Shanghai, Pudong District were involved. According to the measurement and analysis of the unaided visual acuity (VA), AL, CRC, AL/CRC ratio, astigmatism and other refractive parameters, the data distribution and reference range were obtained. RESULTS: Uncorrected VA of examined children was 0.23±0.08 (logMAR, mean±SD) [95% confidence interval (CI) range ≤0.36]; AL was 22.10±0.79 mm (95%CI 20.55-23.65); CRC was 7.86±0.26 mm (95%CI, 7.35-8.37); AL/CRC ratio was 2.81±0.12 (95%CI, 2.57-3.05). The median of astigmatism was -0.5 D, a total of 56.3% had astigmatism -1.50 D; 71% were astigmatism with the rule. Eye-specific analyses were conducted. Statistical difference of VA was in right and left eyes. There were no significant differences between two eyes of AL, CRC, AL/CRC ratio and astigmatism (P>0.05). CONCLUSION: VA and AL/CRC ratio reference could be used to assess refractive development in children and screening uncorrected refractive errors or amblyopia. Astigmatism needs to be considered in the diagnosis.

Purpose. To evaluate the ocular pharmacokinetic properties of subretinal conbercept injection in vitrectomized rabbit eyes and to compare them with those by intravitreal injection. Methods. The following groups of New Zealand white rabbits received conbercept injections (0.5 mg/0.05 ml): a subretinal group (subretinal injection in vitrectomized eyes), an intravitreal group (intravitreal injection in vitrectomized eyes), and a control group (intravitreal injection in nonvitrectomized eyes). Drug concentrations in the aqueous humor (AH), the vitreous humor (VH), and the retina were measured by the enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated. Ophthalmic B-ultrasonography, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to evaluate the safety of subretinal injection. Results. On the 28th day after injection, the drug level in the subretinal group was significantly higher than that in the intravitreal group in the AH (0.90 ± 0.25 μg/ml and 0.11 ± 0.07 μg/ml, P

A new type of conjugated polybenzimidazole (CPBI) was synthesized through a simple polycondensation reaction without metal catalysis, and N-alkylation modification was carried out to solve the problems of solubility and fluorescence properties. A series of nano-microsphere polymers CPBIn with large conjugation, good solubility, and strong fluorescence has been successfully used as “turn-off” fluorescent probes for the first time. The results show that, under suitable N-alkylation conditions, the obtained CPBIn can be used as a highly sensitive and selective fluorescent probe for the detection of Cu2+ and Zn2+ at the same time, and their detection limits are both nM levels. In addition, CPBI2 can be designed as an ultra-sensitive IMPLICATION logic gate at the molecular level, cyclically detecting Cu2+. With the test paper containing CPBI2, easy and quick on-site detection can be achieved. This research provides a new idea for the brief synthesis of multifunctional materials.

AIM: To analyze cytokines as biomarkers for evaluation of severity of glaucoma. METHODS: This was a prospective case-control study including 29 eyes with glaucoma. Besides, 28 eyes with senile cataract were used as control. Patients were classified into four groups: acute angle closure glaucoma (AACG), chronic angle closure glaucoma (CACG), primary open angle glaucoma (POAG) and senile cataract. Undiluted vitreous samples were collected, then vitreous concentrations of 9 types of cytokines were determined by cytometric bead assay system: γ-interferon (IFNg), interleukin (IL)-10, IL-2, IL-4, IL-5, interferon-γ-inducible protein (IP)-10, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF) -α, and vascular endothelial growth factor (VEGF). We also recorded the intraocular pressure (IOP) of patients in each group and Pearson correlated analysis was performed to analysis the correlation between each type of cytokine with IOP. RESULTS: Vitreous levels of IL-2, IL-5, MCP-1, TNF-α and IP-10 were significantly higher (P

Abstract Background Anti-angiogenesis treatments are the most commonly used treatments for the vision loss caused by exudative age-related macular degeneration (AMD), in which the anti-vascular endothelial growth factor (VEGF) drugs with ranibizumab and bevacizumab are current standard treatments. However, the outcome of anti-VEGF therapeutics is not uniform in all patients. Methods We performed a literature-based meta-analysis including, five published studies relevant to HTRA1 and response to anti-VEGF treatment (bevacizumab or ranibizumab). Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed- and random-effects models. Sensitivity analysis and meta-regression were also performed. Q-statistic test and Egger’s test was used to evaluate heterogeneity and publication bias respectively. Results Overall, no association between the rs11200638 polymorphism in HTRA1 gene and the anti-VEGF treatment response was found in the genotype GG versus AA (OR = 1.06; 95% CI: 0.77 to 1.48; P = 0.98), genotype GA versus AA (OR = 1.11; 95% CI: 0.83 to 1.47; P = 0.93), genotype GG + GA versus AA (OR = 1.22; 95% CI: 0.94 to 1.57; P = 0.09), and allele G versus A (OR = 0.92; 95% CI: 0.78 to 1.08; P = 0.14). In the subgroup analysis by ethnicity Caucasian population, and a significant association was still not observed in all genetic models. Sensitivity analysis indicated the robustness of our findings, and no publication bias was observed in our meta-analysis. Conclusions This study shows that there was no association between the polymorphism rs11200638 in HTRA1 gene and response to anti-VEGF treatment of exudative AMD. However, more studies are needed to further prove the conclusion of present study, especially well-designed and high quality randomised controlled trials or intervention studies.

Abstract An atom‐precise Cu0‐containing copper cluster, Cu14(C2B10H10S2)6(CH3CN)8 (abbreviated as Cu14‐8CH3CN) is reported, which is synthesized via a simultaneous reduction strategy and fully characterized by single‐crystal X‐ray diffraction, ESI‐TOF‐MS, and X‐ray photoelectron spectroscopy. Cu14‐8CH3CN is the only copper cluster that has a virtually identical silver structural analog, i.e., Ag14(C2B10H10S2)6(CH3CN)8 (hereafter as Ag14‐8CH3CN). Nevertheless, density functional theory calculations reveal that the electronic structure of Cu14‐8CH3CN differs significantly from the superatom electronic configuration of Ag14‐8CH3CN. Moreover, Cu14‐8CH3CN shows room‐temperature luminescence and good electrocatalytic activities in the ethanol oxidation reaction and detection of H2O2. This pair of unprecedented analogous molecular nanoscale systems offer an ideal platform to investigate the fundamental differences between copper and silver in terms of catalytic activity and optical properties.

The Japanese encephalitis virus (JEV) is a Culex mosquito-borne flavivirus and is the pathogenic agent of Japanese encephalitis, which is the most important type of viral encephalitis in the world. Macrophages are a type of pivotal innate immunocyte that serve as sentinels and respond quickly to pathogen invasions. However, some viruses like JEV can hijack macrophages as a refuge for viral replication and immune escape. Despite their crucial involvement in early JEV infection, the transcriptomic landscapes of JEV-infected macrophages are void. Here, by using an in situ JEV infection model, we investigate the transcriptomic alteration of JEV-infected peritoneal macrophages. We found that, upon JEV infection, the macrophages underwent M1 polarization and showed the drastic activation of innate immune and inflammatory pathways. Interestingly, almost all the programmed cell death (PCD) pathways were activated, especially the apoptosis, pyroptosis, and necroptosis pathways, which were verified by the immunofluorescent staining of specific markers. Further transcriptomic analysis and TUNEL staining revealed that JEV infection caused apparent DNA damage. The transcriptomic analysis also revealed that JEV infection promoted ROS and RNS generation and caused oxidative stress, which activated multiple cell death pathways. Our work uncovers the pivotal pathogenic roles of oxidative stress and multiple PCD pathways in JEV infection, providing a novel perspective on JEV−host interactions.

Flaviviruses including Dengue virus (DENV), Yellow fever virus (YFV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) are global health problems that caused several serious diseases such as fever, hemorrhagic fever, and encephalitis in the past century. Recently, Zika virus (ZIKV) which spreads from Asia to American and causes millions of infections emerges as a new dangerous member of the genus of Flavivirus. Unlike other well-known flaviviruses, ZIKV can be transmitted sexually and infect testes in murine models. Its impacts on sperm functions, and the exact susceptible cells, however, are not entirely clear. To investigate these issues, we infected interferon α/β and γ receptors deficient AG6 mice with ZIKV and examined the outcomes of infection using an assortment of physiological, histopathological, immunological, and virological techniques. We found that infected mice displayed signs of reproductive system disorder, altered androgen levels in serum, and high viral load in semen and testes. Additionally, histopathological examinations revealed marked atrophy of seminiferous tubules and significant reduction in lumen size. Notably, these were accompanied by positive staining of ZIKV antigens on sertoli cells, detection of viral particles and vacuole changes within cytoplasm of sertoli cells. The susceptibility of sertoli cells to ZIKV was further validated in vitro study using cell lines. Importantly, the disruption of tight junctions within testis and altered sperm morphology were also observed in ZIKV infected mice. It is well-known that tight junctions formed by adjacent sertoli cells are major component of blood testis barrier, which plays important roles in maintenance of microenvironment for spermagenesis in testis. Taken together, these results demonstrate that sertoli cells are susceptible to ZIKV infection, which results in the disruption of tight junctions in testis and causes abnormal spermatogenesis in mice. These results also imply that long-term impact of ZIKV infection on human male reproductive system requires close monitoring.

AIM:To determine the effects of epidermal growth factor (EGF) on the proliferation and migration of Müller cell line Moorfields/Institute of Ophthalmology-Müller 1 (MIO-M1), and its related molecular mechanisms under normal and oxidative stress conditions.METHODS: Müller cells were cultured with different concentrations of EGF in the presence or absence of varied amounts of H2O2 and glucose oxidase (GO) which induced oxidative stress. The proliferation and migration of Müller cells were examined by 5-Bromo-2-deoxyUridine (BrdU), MTT assay, Transwell assay and scratch wound healing assays. The cell viability was determined with the MTT assay. The secretion of EGF by Müller cells was evaluated by ELISA. Western blot was performed to detect the activation of extracellular regulated protein kinases (ERK)1/2 and Akt signal pathways.RESULTS:EGF stimulated the proliferation and migration of Müller cells in a concentration-dependent manner in vitro. Underoxidative damage condition,2h of pretreatment with 10-100 ng/mL EGF can mostly inhibit 50% lethal dose of 0.08 mmol/L H2O2-induced cell damage. The Western blot results showed that after Müller cells were exposed to varying EGF for 24h, Akt and ERK1/2 were phosphorylated in a dose-dependent manner. In the presence of the LY294002, the potent PI3K inhibitor, the p-Akt was significantly attenuated.CONCLUSION:EGF may induce the proliferation and migration of human Müller cells through the Akt and the ERK1/2 signal pathways, and induce PI3K-mediated glioprotective effect under oxidative stress.

The present study was performed to examine the effect of 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) on the rate of cell proliferation and apoptosis induction in the PC3, human prostate carcinoma cell line. The cell viability was assayed by using sulphorhodamine B staining and apoptosis by annexin V and flow cytometry analyses. The results revealed that BHP treatment in PC3 cells caused a significant reduction in the rate of cell proliferation in dose- and time-dependent manner. Compared to the un-treated cells, the formation of HUVEC tubes was markedly inhibited on treatment with BHP at a concentration of 30 µM. Further investigation revealed the expression of HMGB1, IL-6 and IL-8, pro-inflammatory cytokines was also inhibited on treatment with BHP. Therefore, BHP treatment plays an important role in inducing apoptosis in the prostrate cells and can be of therapeutic value for the prostate cancer treatment.

PurposeTo investigate whether the polymorphism rs800292 (184G>A, I62V) in the complement factor H gene is associated with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD), in Asian populations.MethodsA comprehensive literature search was performed in PubMed, Medline, Web of Science, and reference lists. A system review and meta-analysis of the association between I62V and PCV and/or nAMD were performed from 8 studies involving 5,062 subjects. The following data from individual studies were extracted and analyzed: 1) comparison of I62V polymorphisms between PCV and controls; 2) comparison of I62V polymorphisms between PCV and nAMD. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models. The Q-statistic test was used to assess heterogeneity, and Egger's test was used to evaluate publication bias. Sensitivity analysis and cumulative meta-analysis were also performed.ResultsThe I62V polymorphism showed a significant summary OR1 for genotype GA+GG versus homozygous genotype AA was 3.18 (95% CI, 2.51-4.04, PConclusionsOur analysis provides evidence that the I62V polymorphism is associated with an increased risk of PCV. The variant of I62V could be a promising genetic biomarker of PCV in Asian populations.

Algal bloom is a typical phenomenon of the eutrophication of rivers and lakes and makes the water dirty and smelly. It is a serious threat to water security and public health. Most scholars studying solutions for this pollution have studied the principles of remediation approaches, but few have studied the decision-making and selection of the approaches. Existing research uses simplex decision-making information which is highly subjective and uses little of the data from water quality sensors. To utilize these data and solve the rational decision-making problem, a novel group decision-making method is proposed using the sensor data with fuzzy evaluation information. Firstly, the optimal similarity aggregation model of group opinions is built based on the modified similarity measurement of Vague values. Secondly, the approaches’ ability to improve the water quality indexes is expressed using Vague evaluation methods. Thirdly, the water quality sensor data are analyzed to match the features of the alternative approaches with grey relational degrees. This allows the best remediation approach to be selected to meet the current water status. Finally, the selection model is applied to the remediation of algal bloom in lakes. The results show this method’s rationality and feasibility when using different data from different sources.

Manipulation is an important issue for both developed and emerging stock markets. Many efforts have been made to detect manipulation in stock markets. However, it is still an open problem to identify the fraudulent traders, especially when they collude with each other. In this paper, we focus on the problem of identifying the anomalous traders using the transaction data of eight manipulated stocks and forty-four non-manipulated stocks during a one-year period. By analyzing the trading networks of stocks, we find that the trading networks of manipulated stocks exhibit significantly higher degree-strength correlation than the trading networks of non-manipulated stocks and the randomized trading networks. We further propose a method to detect anomalous traders of manipulated stocks based on statistical significance analysis of degree-strength correlation. Experimental results demonstrate that our method is effective at distinguishing the manipulated stocks from non-manipulated ones. Our method outperforms the traditional weight-threshold method at identifying the anomalous traders in manipulated stocks. More importantly, our method is difficult to be fooled by colluded traders.

The title compound, C20H30ClNO3, was obtained via a tandem asymmetric Michael addition–elimination reaction of (5S)-3,4-dichloro-5-(l-menthyloxy)-2(5H)-furanone and diallylamine in the presence of potassium fluoride. The molecular structure contains an approximately planar five-membered furanone ring [maximum atomic deviation = 0.0221 (3) Å] and a six-membered ring adopting a chair conformation.

In the title compound, C17H26ClNO3, both cyclohexyl rings have chair conformations. In the crystal, molecules are linked by weak intermolecular C—H...O hydrogen bonds.

The title compound, C16H26ClNO3 contains one almost planar furanone ring [maximum deviation of 0.021 (2) Å for the O atom] with a stereogenic center (S) and one cyclohexane ring which displays a chair conformation and has three stereogenic centers [S at the C atom bearing the isopropyl group, R at the C atom attached to the O atom and R at the C atom bearing the methyl group].

There are two molecules in the asymmetric unit of title compound, C11H16BrNO3, which was obtained via the tandem Michael addition–elimination reaction of 3,4-dibromo-5-methoxyfuran-2(5H)-one and 4-methylpiperidine in the presence of potassium fluoride. The furanone rings are approximately planar [maximum atomic deviations of 0.026 (2) and 0.015 (2) Å, respectively]. The packing is stabilized by weak intermolecular C—H...O and C—H...Br interactions.

The title compound, C18H26ClNO3, was obtained via a tandem asymmetric Michael addition–elimination reaction of 3,4-dichloro-5-(S)-(l-menthyloxy)furan-2(5H)-one and 2,5-dihydro-1H-pyrrole in the presence of potassium fluoride. In the molecule, the nearly planar dihydropyrrole ring [maximum atomic deviation = 0.019 (3) Å] is oriented at a dihedral angle of 10.73 (8)° to the the nearly planar furanone ring [maximum atomic deviation = 0.011 (2) Å]; the cyclohexane ring adopts a chair conformation. In the crystal, molecules are linked via weak intermolecular C—H...O hydrogen bonds, forming supramolecular chains running along the b axis.

The title compound, C20H30BrNO3, was obtained via a tandem asymmetric Michael addition–elimination reaction of 3,4-dibromo-5-(S)-(l-menthyloxy)-2(5H)-furanone and diallylamine in the presence of potassium fluoride. In the molecule, the five-membered furanone ring is approximately planar [maximum atomic deviation = 0.030 (3) Å], and the six-membered cyclohexane ring adopts a chair conformation.

The title compound, C20H33ClN2O3, was obtained via a tandem asymmetric Michael addition–elimination reaction of 3,4-dichloro-5-(S)-(l-menthyloxy)furan-2(5H)-one and 1-ethylpiperazine in the presence of potassium fluoride. The molecular structure contains an approximately planar five-membered furanone ring [maximum atomic deviation = 0.024 (2) Å] and two six-membered rings adopting chair conformations. Weak intermolecular C—H...O hydrogen bonding is present in the crystal structure.

The title compound, C8H10ClNO5, was obtained via a tandem Michael addition–elimination reaction of 3,4-dichloro-5-methoxyfuran-2(5H)-one and glycine methyl ester in the presence of triethylamine. The molecular structure contains an approximately planar [maximum atomic deviation = 0.010 (2) Å] five-membered furanone ring. The crystal packing is stabilized by intermolecular N—H...O and weak C—H...O hydrogen bonding.

In the the title compound, C19H18BrNO3, the furanone ring is almost planar [maximum atomic deviation = 0.019 (3) Å] and is nearly perpendicular to the two phenyl rings, making dihedral angles of 88.96 (17) and 87.71 (17)°. Intermolecular C—H...O hydrogen bonding is present in the crystal structure.

The neutral N-heterocycle in the title centrosymmetric dinuclear compound, [Ag2(NO3)2(C8H15N3)2], bridges two metal atoms through its imino N atoms. The N—Ag—N skeleton is bent [N—Ag—N = 127.2 (3)°]; as one of two O atoms of the nitrate anion is nearly coplanar with this N—Ag—N skeleton [Ag—O = 2.63 (1) Å], the coordination geometry around the AgI atom is regarded as trigonal-planar. One of the two isopropyl groups is disordered over two positions in respect of the methyl groups in a 1:1 ratio. In the crystal structure, intermolecular N—H...O hydrogen bonding is observed between the nitrate groups and triazole ligands.

The title compound, C19H30BrNO5, was obtained via a tandem asymmetric Michael addition–elimination reaction of 3,4-dibromo-5-[(S)-l-menthyloxy]furan-2(5H)-one and l-valine in the presence of potassium hydroxide. The molecular structure contains an approximately planar (r.m.s. deviation = 0.0204 Å) five-membered furanone ring and a six-membered menthyloxy ring adopting a chair conformation. The crystal packing is stabilized by intermolecular O—H...O and N—H...O hydrogen bonding.

The Ag atom in the title compound, [Ag(C13H10N2)2]NO3, shows an approximately linear coordination [N–Ag–N 162.6 (4)°]. The coordination geometry is distorted towards square-planar owing to two long Ag...O interactions [Ag...O = 2.634 (15) and 2.861 (13) Å]. In the crystal structure, the Ag atom lies on a special position of 2 site symmetry; the nitrate anion is disordered about the special position. The crystal under investigation was a racemic twin with a 33% minor twin component.

The title compound, C19H30ClNO5, was obtained by the tandem asymmetric Michael addition–elimination reaction of (5S)-3,4-dichloro-5-(l-menthyloxy)furan-2(5H)-one and l-valine in the presence of potassium hydroxide. The furanone unit is approximately planar (r.m.s. deviation = 0.0204 Å) and the six-membered cyclohexane ring adopts a chair conformation. The crystal structure is stabilized by a network of O—H...O and N—H...O hydrogen bonds.

The title compound, C17H26ClNO5, was prepared via a tandem asymmetric Michael addition–elimination reaction of (5S)-3,4-dichloro-5-(l-menthyloxy)furan-2(5H)-one and l-alanine in the presence of potassium hydroxide. The five-membered furanone ring is approximately planar while the six-membered menthyloxy ring adopts a chair conformation. The crystal packing is stabilized by intermolecular O—H...O and N—H...O hydrogen bonds.

The title compound, C34H54Br2N2O6, was obtained by the Michael addition–elimination reaction of (5S)-5-(l-menthyloxy)-3,4-dibromofuran-2(5H)-one with 1,6-hexanediamine in the presence of triethylamine. The crystal structure contains two chiral five-membered furanone rings, in twist and envelope conformations, and two six-membered cyclohexane rings in chair conformations.

Despite their widespread application in planetary and earth sciences in the past two decades, thallium isotopic compositions have been determined via MC-ICP-MS with instrumental mass bias corrected by employing a combination of lead doping and standard-sample bracketing. Residual Pb, either from the sample matrix or contamination, may significantly distort the isotope ratio of Pb for mass bias correction, thereby affecting the accuracy of Tl isotope measurement. In this study, we employed 186W/184W (NIST SRM 3163 W) instead of 208Pb/206Pb (NIST SRM 981 Pb) to correct instrumental mass bias during the measurement of Tl isotopic compositions through MC-ICP-MS. The plot of ln(186W/184W) vs. ln(205Tl/203Tl) shows a strong linear correlation (R2 > 0.993) in the repeated analyses of NIST SRM 997 Tl using W. Two pure Tl standards, Fluka Tl and GSB Tl, produced 3205TlNIST 997 values of -1.9 ± 0.7 (2SD, n = 97) and 0.8 ± 0.7 (2SD, n = 31), respectively. The 3205TlNIST 997 of five geological reference materials (SCo-1, GSS-6, GSP-2, NOD-P-1, and NOD-A-1) are also reported here, and the external reproducibility of these results is better than 0.08& (2SD). 3205TlNIST997 values are in good agreement with previously published values determined using Pb doping to correct mass bias, demonstrating that W can serve as a calibrator and facilitate high-precision 3205TlNIST 997 measurement of geological materials. [ABSTRACT FROM AUTHOR]