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The clinical treatment of hepatocellular carcinoma (HCC) is still a heavy burden worldwide. Intracellular microRNAs (miRNAs) commonly express abnormally in cancers, thus they are potential therapeutic targets for cancer treatment. miR-21 is upregulated in HCC whereas miR-122 is enriched in normal hepatocyte but downregulated in HCC. In our study, we first generated a reporter genetic switch compromising of miR-21 and miR-122 sponges as sensor, green fluorescent protein (GFP) as reporter gene and L7Ae:K-turn as regulatory element. The reporter expression was turned up in miR-21 enriched environment while turned down in miR-122 enriched environment, indicating that the reporter switch is able to respond distinctly to different miRNA environment. Furthermore, an AAT promoter, which is hepatocyte-specific, is applied to increase the specificity to hepatocyte. A killing switch with AAT promoter and an apoptosis-inducing element, Bax, in addition to miR-21 and miR-122 significantly inhibited cell viability in Huh-7 by 70 % and in HepG2 by 60 %. By contrast, cell viability was not affected in five non-HCC cells. Thus, we provide a novel feasible strategy to improve the safety of miRNA-based therapeutic agent to cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Age-related macular degeneration (AMD) is a common retinal neurodegenerative disease among the elderly. Neovascular AMD (nAMD), a leading cause of AMD-related blindness, involves choroidal neovascularization (CNV), which can be suppressed by anti-angiogenic treatments. However, current CNV treatments do not work in all nAMD patients. Here we investigate a novel target for AMD. Granzyme B (GzmB) is a serine protease that promotes aging, chronic inflammation and vascular permeability through the degradation of the extracellular matrix (ECM) and tight junctions. Extracellular GzmB is increased in retina pigment epithelium (RPE) and mast cells in the choroid of the healthy aging outer retina. It is further increased in donor eyes exhibiting features of nAMD and CNV. Here, we show in RPE-choroidal explant cultures that exogenous GzmB degrades the RPE-choroid ECM, promotes retinal/choroidal inflammation and angiogenesis while diminishing anti-angiogenic factor, thrombospondin-1 (TSP-1). The pharmacological inhibition of either GzmB or mast-cell degranulation significantly reduces choroidal angiogenesis. In line with our in vitro data, GzmB-deficiency reduces the extent of laser-induced CNV lesions and the age-related deterioration of electroretinogram (ERG) responses in mice. These findings suggest that targeting GzmB, a serine protease with no known endogenous inhibitors, may be a potential novel therapeutic approach to suppress CNV in nAMD., (© 2024. The Author(s).)

Zika virus (ZIKV) is an emerging flavivirus that causes congenital syndromes including microcephaly and fetal demise in pregnant women. No commercial vaccines against ZIKV are currently available. We previously generated a chimeric ZIKV (ChinZIKV) based on the Chaoyang virus (CYV) by replacing the prME protein of CYV with that of a contemporary ZIKV strain GZ01. Herein, we evaluated this vaccine candidate in a mouse model and showed that ChinZIKV was totally safe in both adult and suckling immunodeficient mice. No viral RNA was detected in the serum of mice inoculated with ChinZIKV. All of the mice inoculated with ChinZIKV survived, while mice inoculated with ZIKV succumbed to infection in 8 days. A single dose of ChinZIKV partially protected mice against lethal ZIKV challenge. In contrast, all the control PBS-immunized mice succumbed to infection after ZIKV challenge. Our results warrant further development of ChinZIKV as a vaccine candidate in clinical trials.

The AIM2 inflammasome represents a multifaceted oligomeric protein complex within the innate immune system, with the capacity to perceive double-stranded DNA (dsDNA) and engage in diverse physiological reactions and disease contexts, including cancer. While originally conceived as a discerning DNA sensor, AIM2 has demonstrated its capability to discern various nucleic acid variations, encompassing RNA and DNA-RNA hybrids. Through its interaction with nucleic acids, AIM2 orchestrates the assembly of a complex involving multiple proteins, aptly named the AIM2 inflammasome, which facilitates the enzymatic cleavage of proinflammatory cytokines, namely pro-IL-1β and pro-IL-18. This process, in turn, underpins its pivotal biological role. In this review, we provide a systematic summary and discussion of the latest advancements in AIM2 sensing various types of nucleic acids. Additionally, we discuss the modulation of AIM2 activation, which can cause cell death, including pyroptosis, apoptosis, and autophagic cell death. Finally, we fully illustrate the evidence for the dual role of AIM2 in different cancer types, including both anti-tumorigenic and pro-tumorigenic functions. Considering the above information, we uncover the therapeutic promise of modulating the AIM2 inflammasome in cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Vesicle-associated membrane protein 7 (VAMP7) plays oncogenic roles in cancers. However, its clinical significance in breast cancer (BC) tissues remains unknown., Objective: To elucidate the clinical implications of VAMP7, as well as its involvement in the tumor microenvironment and molecular pathways of breast cancer., Methods: BC (n=100) and non-cancerous breast tissues (n= 100) were collected for an immunohistochemical experiment (1:200). The protein expression level of VAMP7 was determined by using a semi-quantitative scoring method. High-throughput RNA-sequencing data of BC tissues were analyzed to confirm the mRNA expression trend of VAMP7. Additionally, the largest BC prognosis cohort data were collected to mine the potential impact VAMP7 has on BC progression. The association between VAMP7 and the microenvironment of BC was evaluated by using a CIBERSORT algorithm. Moreover, we explored the co-expressed molecular mechanisms of VAMP7 in BC by calculating Pearson correlation coefficients and overexpressed genes. Finally, the biological mechanism underlying the relationship between VAMP7 and the key pathways was also explored using gene set enrichment analysis (GSEA). Potential therapeutic strategies were predicted targeting VAMP7., Results: VAMP7 protein was significantly over-expressed in BC tissue than that in controls (p< 0.001). Compared with 459 normal breast tissues and 113 non-cancerous breast tissues, the expression level of VAMP7 mRNA was significantly increased in 1111 BC tissues. CD4+T cells, macrophages, and naïve B cells had a higher infiltration rate in BC tissues with high VAMP7 expression, while regulatory T cells and CD8+T cells had a lower infiltration rate. Over-expressed VAMP7 was associated with macrophages activation and transition from M1 to M2 polarization. Upregulated VAMP7 could predicted poorer OS, DMFS, PPS, and RFS outcomes. Upregulated VAMP7 co-expressed genes were significantly enriched in the cell cycle checkpoints. GSEA confirmed that over-expressed VAMP7 are markedly associated with functional enrichment in cell cycle related categories, including mitotic spindle, G2M checkpoint, and E2F targets. KU-55933 was predicted as a putative therapeutic drug for BC targeting VAMP7., Conclusions: VAMP7 was upregulated in BC tissue and correlated with poor prognosis of BC patients. VAMP7 may promote BC progression by targeting the cell cycle pathway.

Advanced-stage ovarian cancer is usually associated with peritoneal carcinomatosis. This study evaluates the prognostic role of the Peritoneal Cancer Index (PCI) in predicting the survival of patients with ovarian cancer. A literature search was conducted in electronic databases (Google Scholar, PubMed, Ovid, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to estimate survival with low and high PCI scores and to pool hazard ratios (HR) of survival between lower and higher PCI scores. A total of 20 studies (2588 patients) were included. Median follow-up was 39 months [95%CI: 25, 54]. Complete cytoreduction rate was 80% [95% CI: 73, 87]. The median PCI score was 11.3 [95% CI: 9.9, 12.7]. Median survival was 56.7 months [95% CI: 45.2, 68.2] with below and 28.8 months [95% CI: 23.0, 34.6] with above any PCI cutoff. Most studies used PCI cutoffs between 10 and 20. The median progression-free survival was 23.7 months [95% CI: 16.5, 30.8] with below and 11.9 months [95% CI: 5.9, 17.9] with above any PCI cutoff. 5-year survival rates were 61.3% [95% CI: 49.9, 72.8] with PCI<10 cutoffs, 21.7% [95% CI: 11.6, 31.8] with PCI>10 cutoffs, 50.1% [95% CI: 39.0, 61.2] with PCI<20 cutoffs, and 21.7% [95% CI: 16.2, 27.1] with PCI>20 cutoffs. Pooled analysis of HRs showed that a higher PCI score was associated with worse survival in both univariate (HR 2.14 [95%CI: 1.63, 2.66]) and multivariate (HR 1.10 [95% CI: 1.02, 1.18]) analyses. In a set of studies that used varying PCI cutoffs, the PCI has been found to have a significant inverse association with the survival of patients with advanced ovarian cancer who underwent cytoreductive surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The management of older aneurysmal subarachnoid haemorrhage (aSAH) cases is a clinical challenge. This study aimed to analyse the survival and functional outcomes in older aSAH patients (age ≥ 70 years) to provide evidence for making treatment decisions for such patients., Methods: We performed a 2-year follow-up analysis of the Chinese Multi-Centre Cerebral Aneurysm Database for older patients suffering from aSAH from 2017 to 2020. A survival analysis was used to investigate the mean survival and hazard ratios for death. Binary logarithmic regression was performed to investigate the odds ratio for independent survival and dependent survival., Results: A total of 1,136 consecutive older patients with aSAH were assessed in this study, and 944 patients (83.1%) were followed up. The overall mean survival was 37.79 ± 1.04 months. A total of 380 (40.25%) patients died within 2 years after aSAH. In survival analysis, the predictors of mortality were older age, intracerebral haemorrhage (ICH) history, Hunt-Hess (H-H) grade, World Federation of Neurosurgical Societies (WFNS) grade and operative treatment decreased the risk of mortality compared to conservative treatment. In binary logarithmic regression, the predictors of dependent survival were hypertension, diabetes, WFNS grade., Conclusions: The risk for 2-year mortality after aSAH increases markedly with older age, ICH history, H-H grade and WFNS grade. Risk factors for 2-year dependent survival were associated with hypertension, diabetes and WFNS grade in older patients with aSAH. Operative treatment markedly decreased mortality but did not significantly decrease the morbidity of dependent survival compared to conservative treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Semiconducting polymer chains constitute the building blocks for a wide range of electronic materials and devices. However, most of their electrical characteristics at the single-molecule level have received little attention. Elucidating these properties can help understanding performance limits and enable new applications. Here, coupled ionic-electronic charge transport is exploited to measure the quasi-1D electrical current through long single conjugated polymer chains as they form transient contacts with electrodes separated by ≈10 nm. Fluctuations between internal conformations of the individual polymers are resolved as abrupt, multilevel switches in the electrical current. This behavior is consistent with the theoretical simulations based on the worm-like-chain (WLC) model for semiflexible polymers. In addition to probing the intrinsic properties of single semiconducting polymer chains, the results provide an unprecedented window into the dynamics of random-coil polymers and enable the use of semiconducting polymers as electrical labels for single-molecule (bio)sensing assays., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

A series of bifunctional Ln(III)-based coordination polymers (CPs) {Ln(L)(DMA) 2 (NO 3 )} n [Ln(III) = Eu ( 1 ), Gd ( 2 ), and Dy ( 3 ); organic ligand H 2 L = 2,2'-(1,3,5,7-tetrahydroxyoctahydro-4,8-ethanopyrrolo[3,4- f ]isoindole-2,6(1 H ,3 H )-diyl)diacetic acid)] have been successfully synthesized. CPs 1 - 3 are isostructural and constructed from the dimeric Ln 2 unit in which two adjacent Ln III ions are bridged by two μ 3 -carboxyl oxygens, and the Ln 2 dimeric unit is connected by two NO 3 - ions, four DMA molecules, and four completely protonated L 2- ligands forming a 2D layer structure. The magnetic research reveals that CP 2 shows a significant cryogenic magnetocaloric effect (-Δ S m = 22.9 J kg -1 K -1 ; T = 2.0 K and Δ H = 7.0 T), whereas CP 3 exhibits slow magnetic relaxation property under H dc = 0 Oe field. Additionally, the luminescence explorations revealed that CP 1 can act as a recyclable luminescent probe for pollutant acetylacetone among various small organic solvent molecules, and the corresponding detection limit is 10 -7 mol/L. More importantly, CP 1 also exhibits good catalytic performance in the cycloaddition reaction of CO 2 and epoxides or cyanamides under mild conditions. As far as we know, CP 1 represents the first bifunctional lanthanide homogeneous catalyst that can efficiently catalyze the reaction of cyanamides/epoxides with CO 2 simultaneously.

It is difficult and challenging to design and construct high-nuclearity Ln(III)-based clusters due to the high coordination numbers and versatile coordination geometries of Ln(III) ions. Herein, two novel octanuclear Ln(III)-based clusters [Ln 8 (H 2 L - ) 4 (HL 2- ) 4 (NO 3 ) 6 (CO 3 ) 2 ](NO 3 ) 2 ·2CH 3 CN (Ln = Nd (1) and Sm (2)) have been synthesized under solvothermal conditions. The X-ray single analysis reveals that both 1 and 2 are octanuclear structures and the eight central Ln(III) ions are bridged by two CO 3 2- anions. Catalytic study revealed that 1 and 2 can effectively catalyze the cycloaddition reaction of CO 2 and aziridines or epoxides simultaneously under mild conditions. What is more, cluster 1, as a heterogeneous catalyst, can be reused at least three times without obvious loss in catalytic activity for coupling of CO 2 and epoxides. To our knowledge, cluster 1 is the first Ln(III)-based cluster catalyst used for the conversion of CO 2 with aziridines or epoxides simultaneously. This work provides a successful strategy to integrate high-nuclear Ln(III)-based clusters for CO 2 conversion, which may open a new space for the construction of multifunctional high-nuclear Ln(III)-based clusters as efficient catalysts for CO 2 conversion.

The genus Flavivirus is a group of arthropod-borne single-stranded RNA viruses, which includes important human and animal pathogens such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), Dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Tick-borne encephalitis virus (TBEV). Reverse genetics has been a useful tool for understanding biological properties and the pathogenesis of flaviviruses. However, the conventional construction of full-length infectious clones for flavivirus is time-consuming and difficult due to the toxicity of the flavivirus genome to E. coli . Herein, we applied a simple, rapid, and bacterium-free circular polymerase extension reaction (CPER) method to synthesize recombinant flaviviruses in vertebrate cells as well as insect cells. We started with the de novo synthesis of the JEV vaccine strain SA-14-14-2 in Vero cells using CPER, and then modified the CPER method to recover insect-specific flaviviruses (ISFs) in mosquito C6/36 cells. Chimeric Zika virus (ChinZIKV) based on the Chaoyang virus (CYV) backbone and the Culex flavivirus reporter virus expressing green fluorescent protein (CxFV-GFP) were subsequently rescued in C6/36 cells. CPER is a simple method for the rapid generation of flaviviruses and other potential RNA viruses. A CPER-based recovery system for flaviviruses of different host ranges was established, which would facilitate the development of countermeasures against flavivirus outbreaks in the future.

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly. The pathology of neovascular age-related macular degeneration (nAMD), also known as wet AMD, is associated with an abnormal blood vessel growth in the eye and involves an imbalance of proangiogenic and antiangiogenic factors. Thrombospondin (TSP)-1 and TSP-2 are endogenous matricellular proteins that inhibit angiogenesis. TSP-1 is significantly diminished in eyes with AMD, although the mechanisms involved in its reduction are unknown. Granzyme B (GzmB) is a serine protease with an increased extracellular activity in the outer retina and choroid of human eyes with nAMD-related choroidal neovascularization (CNV). This study investigated whether TSP-1 and TSP-2 are GzmB substrates using in silico and cell-free cleavage assays and explored the relationship between GzmB and TSP-1 in human eyes with nAMD-related CNV and the effect of GzmB on TSP-1 in retinal pigment epithelial culture and an explant choroid sprouting assay (CSA). In this study, TSP-1 and TSP-2 were identified as GzmB substrates. Cell-free cleavage assays substantiated the GzmB proteolysis of TSP-1 and TSP-2 by showing dose-dependent and time-dependent cleavage products. TSP-1 and TSP-2 proteolysis were hindered by the inhibition of GzmB. In the retinal pigment epithelium and choroid of human eyes with CNV, we observed a significant inverse correlation between TSP-1 and GzmB, as indicated by lower TSP-1 and higher GzmB immunoreactivity. In CSA, the vascular sprouting area increased significantly with GzmB treatment and reduced significantly with TSP-1 treatment. Western blot showed significantly reduced expression of TSP-1 in GzmB-treated retinal pigment epithelial cell culture and CSA supernatant compared with that in controls. Together, our findings suggest that the proteolysis of antiangiogenic factors such as TSP-1 by extracellular GzmB might represent a mechanism through which GzmB may contribute to nAMD-related CNV. Future studies are needed to investigate whether pharmacologic inhibition of extracellular GzmB can mitigate nAMD-related CNV by preserving intact TSP-1., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The clinical work of ICU doctors is characterized by high intensity and medical risks, which lead to a highly stressful state for a long time and the occurrence of resignation due to long-term burnout. This study analyzes the correlation between the personal life, hospital work, social opinion, and psychological assessment of ICU physicians and their resignation intention., Subjects and Methods: This study is a multicenter questionnaire on the factors influencing resignation intention among ICU physicians. The study was completed through Critical Care E Institute (CCEI) and China Calm Therapy Research Group Academic Organization (CNCSG) by contacting critical care physicians in 3-A hospitals in 34 provinces in China. The questionnaire was in electronic format, and the results were filled in using the WeChat scan code. The survey included 22 indicators which included basic information about physicians (including gender, marriage, children, and income, etc.), hospital work (weekly working hours, on night duty, hospital environment, the evaluation of hospital's emphasis on medical staff, etc.), and SCL-90 psychological assessment., Results: A total of 1,749 ICU physicians completed the questionnaire. The results showed that 1,208 physicians (69.1%) intended to resign. There were statistical differences between the group's resignation intention and without resignation intention on 13 indicators. These indicators include professional title, night shift every few days, hospital hours/week, income satisfaction, work environment satisfaction, career prospect, and SCL-90 score, etc. (all p<0.05, respectively). The remaining nine indicators were not statistically different between the two groups (all p>0.05, respectively). Logistics analysis showed that working years, hospital hours (h/week), income satisfaction, work environment satisfaction, pride in hospital work, career prospects, and total SCL-90 score were all independent influences on physicians' choice of resignation intention (all p<0.05, respectively). The ROC curves' results showed that all seven indicators' predictive diagnostic value was low, with AUC areas ranging from 0.567 to 0.660. However, the combined diagnostic model of seven indicators has moderate diagnostic value. The AUC area of the model was 0.740 (95% CI: 0.718-0.760), with a sensitivity of 75.99% and specificity of 60.07%., Conclusions: Physicians' income, working years, work environment satisfaction, career prospects, and psychological well-being can influence the choice of physicians' resignation intention in Chinese intensive care units. Government administration and hospitals can develop appropriate policies to enhance doctors working in hospital, thus reducing physicians' resignation choices.

This retrospective study aimed to compare the effects of acupotomy combined with intra-articular injection of sodium hyaluronate (IA-SH) for the treatment of knee osteoarthritis (KOA). Eighty electronic medical records of patients with KOA were retrospectively analyzed. The patients were divided into an intervention group (n = 40, acupotomy plus IA-SH) and a control group (n = 40, IA-SH). Outcome measures included the visual analog scale, the Western Ontario and McMaster Universities Arthritis Index (WOMAC), and adverse events. Outcome data were collected and analyzed before and after treatment. The results of this study showed that there was a greater reduction in the visual analog scale (P < .01) and WOMAC scores (pain, P < .01; stiffness, P < .01; function, P < .01; total, P < .01) in the intervention group than in the control group. In addition, there were no significant differences in adverse events between the 2 groups. In this study, the effects of acupotomy plus IA-SH were superior to those of IA-SH alone for the treatment of patients with KOA. Further prospective studies are required to confirm these findings., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The efficient capture of multi-pollutant residues in food is vital for food safety monitoring. In this study, in-situ-fabricated magnetic MIL-53(Al) metal organic frameworks (MOFs), with good magnetic responsiveness, were synthesized and applied for the magnetic solid-phase extraction (MSPE) of chloramphenicol, bisphenol A, estradiol, and diethylstilbestrol. Terephthalic acid (H 2 BDC) organic ligands were pre-coupled on the surface of amino-Fe 3 O 4 composites (H 2 BDC@Fe 3 O 4 ). Fe 3 O 4 @MIL-53(Al) MOF was fabricated by in-situ hydrothermal polymerization of H 2 BDC, Al (NO 3 ) 3 , and H 2 BDC@Fe 3 O 4 . This approach highly increased the stability of the material. The magnetic Fe 3 O 4 @MIL-53(Al) MOF-based MSPE was combined with high-performance liquid chromatography-photo diode array detection, to establish a novel sensitive method for analyzing multi-pollutant residues in milk. This method showed good linear correlations, in the range of 0.05-5.00 μg/mL, with good reproducibility. The limit of detection was 0.004-0.108 μg/mL. The presented method was verified using a milk sample, spiked with four pollutants, which enabled high-throughput detection and the accuracies of 88.17-107.58% confirmed its applicability, in real sample analysis.

To explore the differences between growth and population dynamics of natural Lycorma delicatula in the plantations and semi-natural forests, the susceptible stages and major suppression factors were determined to provide basis for the prediction and controlling the pest. The development duration and life table of L. delicatula in different habitats were established by using tracking method. The index of exclusion effect for lethal factors and the K -value in each development stage were calculated. The population trends were analyzed through the survival curve and key drivers of population change. The results showed that the development duration of L. delicatula in the plantation habitat and semi-natural habitat was significantly different, with thelatter being 25.7 d longer than the former. There were significant differences in the development duration of 1st-3rd-instars nymphs and pre-oviposition period of adults between these two habitats, but no significant difference in the 4th-instar nymphs. The total mortality rate in the plantation habitat and semi-natural habitat was 83.6% and 98.6%, respectively. The index of population trend in the plantation habitat was significantly higher than that in the semi-natural habitat. The population of L. delicatula increased sharply in the plantation habitat, but showed a decline trend in the semi-natural habitat. All of the survival curves of L. delicatula were Deevey-Ⅲ type, and the EIPCs of the "parasitic natural enemies" in egg stage were the highest in both habitats as 1.3 and 1.6, and the total K values were 0.2 and 0.3, respectively. The regression slopes of K -value of natural enemies were the highest (both 0.6). These findings revealed that the semi-natural habitat played an important role in the natural regulation of L. delicatula .

A series of tetranuclear lanthanide-based clusters [Ln 4 (dbm) 6 (L) 2 (CH 3 OH) 4 ]·2CH 3 OH (Ln(III) = Gd (1), Dy (2), and Ho (3); H 3 L = 2-[(2-(hydroxyimino)propanehydrazide)methyl]-2,3-dihydroxybenzaldehyde, Hdbm = dibenzoylmethane) and octanuclear lanthanide-based clusters [Ln 8 (HL) 10 (CH 3 O) 4 (CH 3 OH) 2 ]·6CH 3 OH (Ln(III) = Gd (4), Dy (5)) were assembled using a polydentate Schiff-base ligand H 3 L and two different β-diketone salts via a solvothermal method, and their structures and magnetic properties have been characterized. Interestingly, β-diketones play an important role in assembling and affecting the structures of Ln 4 to Ln 8 clusters. This is the first use of β-diketone to affect the structures of polynuclear Ln(III)-based clusters from linear-shaped Ln 4 clusters to Ln 8 clusters. Magnetic studies revealed that antiferromagnetic interactions exist in clusters 1-Gd4 and 4-Gd8. More importantly, clusters 1-Gd4 and 4-Gd8 display significant cryogenic magnetic refrigeration properties (-Δ S m = 24.88 J kg -1 K -1 for 1-Gd4 and -Δ S m = 32.52 J kg -1 K -1 for 4-Gd8); the results show that cluster 4-Gd8 exhibits a larger magnetocaloric effect than 1-Gd4. Cluster 2-Dy4 shows remarkable single-molecule magnet (SMM) behavior (Δ E / k B = 67.5 K and τ 0 = 3.06 × 10 -7 s) under a zero dc field, and 5-Dy8 exhibits a field-induced SMM-like behavior (Δ E / k B = 39.83 K and τ 0 = 2.12 × 10 -7 s) under a 5000 Oe dc field.

Background and Aims: Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, their effects on brain stroke risk are unclear. The present meta-analysis aimed to evaluate the effects of PCSK9 inhibitors on brain stroke prevention., Methods and Results: We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov for research published until December 30, 2020, to find randomized controlled trials (RCTs) of PCSK9 inhibitors for brain stroke prevention. Relative risk (RR) and 95% confidence intervals (CIs) were used to represent the outcomes. Seven RCTs with 57,440 participants, including 29,850 patients treated with PCSK9 inhibitors and 27,590 control participants, were included. PCSK9 inhibitors were associated with significant reductions in total brain stroke risk (RR, 0.77; 95% CI, 0.67-0.88; P < 0.001) and ischemic brain stroke risk (RR, 0.76; 95% CI, 0.66, 0.89; P < 0.001) in comparison with the control group. There was no significant difference in cardiovascular mortality (RR, 0.95; 95% CI, 0.84-1.07; P = 0.382) and the risk of hemorrhagic brain stroke (RR, 1.00; 95% CI, 0.66-1.51; P = 0.999) between patients treated with PCSK9 inhibitors and controls. PCSK9 inhibitors did not significantly increase the incidence of neurocognitive adverse events (RR, 1.02; 95% CI, 0.81-1.29; P = 0.85). Moreover, subgroup analysis showed no difference in cognitive function disorder risks among different PCSK9 inhibitors and treatment times., Conclusions: PCSK9 inhibitors significantly reduced the risk of total brain stroke and ischemic brain stroke without increasing the risk of brain hemorrhage and neurocognitive impairment., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The network pharmacology and molecular docking methods were used to explore the mechanism of Jinweitai Capsules in the treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis. The chemical components of herbs in Jinweitai Capsules were collected through TCMSP, CNKI and PubMed. Target prediction was performed through PubChem and SwissTargetPrediction databases; genes relating to acute and chronic gastritis, gastric and duodenal ulcers, chronic colitis were collected from OMIM database; potential targets of Jinweitai Capsules for relevant gastrointestinal diseases were obtained by Venny analysis; DAVID database was used to perform GO and KEGG enrichment analysis; protein interactions were obtained by STRING database and visua-lized by Cytoscape; AutoDockVina was used for molecular docking of AKT1, EGFR, PTPN11 and its reverse-selected chemical components. Potential mechanisms of Jinweitai Capsules in treating relevant gastrointestinal diseases were clarified according to the results of the docking. The results showed 86 potential active ingredients of Jinweitai Capsules and 268 potential targets for treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis. KEGG pathway enrichment analysis showed that 20 pathways relating to acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis mainly involved calcium signaling pathway and chemokine signaling pathway. Molecular docking showed a good binding activity between AKT1, EGFR, PTPN11 and its reverse screening chemical components. Jinweitai Capsules may exert an effect in the treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis by acting on AKT1, EGFR, PTPN11 and other targets in 15 signal pathways relating to cell inflammation and immunity, cell proliferation and apoptosis, Helicobacter pylori infection, and gastrointestinal tract.

Background: Aortic dilation, stiffening, and dissection are common and potentially lethal complications of Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS), which involve abnormal transforming growth factor beta (TGF-β) signalling. The relation of aortic dimensions, stiffness, and biomarker levels is unknown. The objective of this study was to measure aortic dimensions, stiffness, TGF-β and matrix metalloproteinase (MMP) levels, and endothelial function in patients with MFS, and to compare TGF-β levels in patients with MFS receiving different therapeutic regimens., Methods: This was a cohort study of 40 MFS and 4 LDS patients and 87 control participants. Aortic dimension and stiffness indexes, including pulse wave velocity (PWV), were measured using echocardiography and Doppler. Total and free TGF-β and MMP blood levels were measured using Quantikine (R&D Systems, Inc, Minneapolis, MN) and Quanterix (Billerica, MA) kits. Endothelial function was measured using brachial artery flow-mediated dilation., Results: PWV was increased in patients with MFS. There were increased MMP-2 levels in those with MFS but no increase in free or total TGF-β or MMP-9 levels compared with control participants. There was no difference in TGF-β levels between MFS patients receiving no medications, angiotensin receptor blockers, and β-blockers. PWV correlated most strongly with age. Endothelial function showed premature gradual decline in patients with MFS., Conclusions: Despite the increased PWV, monitoring aortic stiffness or TGF-β levels would not be helpful in patients with MFS. TGF-β levels were not increased and the increased MMP-2 levels suggest consideration of a different therapeutic target., (© 2021 The Authors.)

Reperfusion is a critical therapeutic intervention used following acute ischemic stroke; however, it may cause cerebral ischemia/reperfusion injury (CIRI) and aggravate brain damage. Piceatannol (Pic), a hydroxylated analog of resveratrol, has been reported to exhibit anti‑inflammatory effects. However, the detailed molecular mechanisms and its effects on CIRI have not been sufficiently assessed, and, to the best of our knowledge, current methods of prevention of CIRI are limited. The aim of the present study was to investigate the effects of Pic on improving neurological function in a mouse model of CIRI. For the animal experiments, 8‑week‑old C57BL/6 mice were raised and randomly grouped, and an in vivo model of CIRI was established. Mice were administered a low (10 mg/kg/day) or high‑dose (20 mg/kg/d) of Pic 1 h after CIRI orally and once daily for the next 6 days. Neurological dysfunction was assessed using a modified neurological severity score and a rotarod test 1 week after CIRI establishment, and the cognitive status of the mice was assessed using a Morris water maze. Hematoxylin and eosin staining was used to evaluate the histopathological changes. The expression levels of sirtuin 1 (Sirt1), FoxO1, cleaved caspase‑3 (CC‑3), Bax and Bcl‑2 were measured using western blotting. Intracellular reactive oxygen species (ROS) generation, antioxidant enzymes [superoxide dismutase, glutathione (GSH) peroxidase and catalase] and non‑enzymatic antioxidants (GSH) were also detected using spectrophotometry. After inhibition of the Sirt1/FoxO1 pathway, a TUNEL assay was used for the detection of apoptotic cells in vitro and in vivo. The co‑localization of neuron‑specific nuclear protein and CC‑3 was assessing using immunofluorescent staining. Pic improved neurological functions and ameliorated hippocampal neuronal pathology following CIRI. In addition, the expression levels of CC‑3 and Bax and intracellular ROS levels were increased, while levels of antioxidant and non‑enzymatic enzymes were decreased in the mouse model of CIRI. Low and high doses of Pic significantly decreased ROS production and the expression levels of apoptosis‑related proteins, but increased antioxidant enzyme levels. However, a high‑dose of Pic did not result in increased levels of non‑enzymatic enzymes. Furthermore, low and high doses of Pic treatment significantly activated the Sirt1/FoxO1 pathway. Following inhibition of the Sirt1/FoxO1 pathway, the percentage of TUNEL‑positive cells and expression of CC‑3 were increased, and CC‑3 was enriched in neurons. The antioxidant effects of Pic were blocked by inhibition of Sirt1 in vitro and in vivo. In conclusion, these results suggested that Pic may exert a neuroprotective effect against in hippocampal neurons via the Sirt1/FoxO1 pathway.

Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the FBN1 gene that produces wide disease phenotypic variability. The lack of ample genotype-phenotype correlation hinders translational study development aimed at improving disease prognosis. In response to this need, an induced pluripotent stem cell (iPSC) disease model has been used to test patient-specific cells by a proteomic approach. This model has the potential to risk stratify patients to make clinical decisions, including timing for surgical treatment. The regional propensity for aneurysm formation in MFS may be related to distinct smooth muscle cell (SMC) embryologic lineages. Thus, peripheral blood mononuclear cell (PBMC)-derived induced pluripotent stem cells (iPSC) were differentiated into lateral mesoderm (LM, aortic root) and neural crest (NC, ascending aorta/transverse arch) SMC lineages to model MFS aortic pathology. Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) proteomic analysis by tandem mass spectrometry was applied to profile LM and NC iPSC SMCs from four MFS patients and two healthy controls. Analysis revealed 45 proteins with lineage-dependent expression in MFS patients, many of which were specific to diseased samples. Single protein-level data from both iPSC SMCs and primary MFS aortic root aneurysm tissue confirmed elevated integrin αV and reduced MRC2 in clinical disease specimens, validating the iPSC iTRAQ findings. Functionally, iPSC SMCs exhibited defective adhesion to a variety of extracellular matrix proteins, especially laminin-1 and fibronectin, suggesting altered cytoskeleton dynamics. This study defines the aortic embryologic origin-specific proteome in a validated iPSC SMC model to identify novel protein markers associated with MFS aneurysm phenotype. Translating iPSC findings into clinical aortic aneurysm tissue samples highlights the potential for iPSC-based methods to model MFS disease for mechanistic studies and therapeutic discovery in vitro.

Objective: To characterize the epidemiology of severe hand, foot and mouth disease (HFMD) in China from 2008 to 2018 and provide evidence for the prevention and control of severe HFMD. Methods: The incidence data of severe HFMD cases from 2008 to 2018 were collected from the National Notifiable Infectious Diseases Reporting System of Chinese Center for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze distributions, pathogen constituent and change of severe HFMD. Joinpoint regression model was used to analyze the trends of severity rate, proportion of severe cases and severe fatality rate. Results: From 2008 to 2018, a total of 157 065 cases of severe HFMD were reported in China, with an average annual case-severity rate of 1.05/100 000, a severe case proportion of 0.76 % and a severity-fatality rate of 2.34 % . The severity rate and the proportion of severe cases showed a downward trend after 2010, and severe fatality rate decreased significantly after 2014. The severe cases mainly occurred in infants aged ≤3 years (91.47 % ), more boys were affected than girls (1.78∶1). The median age of severe HFMD cases caused by EV-A71 was highest (1.99 years) and increased year by year, other enterovirus infection cases accounted for a higher proportion in infants aged ≤1 year (66.56 % ). The incidence peak occurred during April-July, other enteroviruses replaced EV-A71 as the predominant serotype in 2018 (61.97 % ). The incidence of severe HFMD were high in some provinces in southwestern, central and eastern China. Conclusion: The overall severity rate, proportion of severe cases and severe fatality rate of HFMD in the mainland of China have shown a downward trend. The predominant pathogen in some provinces has changed from EV-A71 to other enteroviruses. It is necessary to strengthen the prevention and control of HFMD in key population, high incidence seasons and areas and carry out the surveillance of various pathogens of HFMD.

Background Male patients with Marfan syndrome have a higher risk of aortic events and root dilatation compared with females. The role androgens play during Marfan syndrome aneurysm development in males remains unknown. We hypothesized that androgens potentiate transforming growth factor beta induced Erk (extracellular-signal-regulated kinase)/Smad activation, contributing to aneurysm progression in males. Methods and Results Aortic diameters in Fbn1 C1039G/+ and littermate wild-type controls were measured at ages 6, 8, 12, and 16 weeks. Fbn1 C1039G/+ males were treated with (1) flutamide (androgen receptor blocker) or (2) vehicle control from age 6 to 16 weeks and then euthanized. p-Erk1/2, p-Smad2, and matrix metalloproteinase (MMP) activity were measured in ascending/aortic root and descending aorta specimens. Fbn1 C1039G/+ male and female ascending/aortic root-derived smooth muscle cells were utilized in vitro to measure Erk/Smad activation and MMP-2 activity following dihydrotestosterone, flutamide or transforming growth factor beta 1 treatment. Fbn1 C1039G/+ males have increased aneurysm growth. p-Erk1/2 and p-Smad2 were elevated in ascending/aortic root specimens at age 16 weeks. Corresponding with enhanced Erk/Smad signaling, MMP-2 activity was higher in Fbn1 C1039G/+ males. In vitro smooth muscle cell studies revealed that dihydrotestosterone potentiates transforming growth factor beta-induced Erk/Smad activation and MMP-2 activity, which is reversed by flutamide treatment. Finally, in vivo flutamide treatment reduced aneurysm growth via p-Erk1/2 and p-Smad2 reduction in Fbn1 C1039G/+ males. Conclusions Fbn1 C1039G/+ males have enhanced aneurysm growth compared with females associated with enhanced p-Erk1/2 and p-Smad2 activation. Mechanistically, in vitro smooth muscle cell studies suggested that dihydrotestosterone potentiates transforming growth factor beta induced Erk/Smad activation. As biological proof of concept, flutamide treatment attenuated aneurysm growth and p-Erk1/2 and p-Smad2 signaling in Fbn1 C1039G/+ males.

Two structurally similar metal-organic frameworks (MOFs) [Dy 2 Cu 4 I 3 (IN) 7 (DMF) 2 ]·DMF ( 1 ) and [Dy 2 Cu 4 I 3 (IN) 7 (DMA) 2 ]·DMA ( 2 ) (HIN = isonicotinic acid) feathering different coordinated solvent molecules were successfully isolated by tuning the types of solvents in the reaction system. Structural tests indicate that 1 and 2 are both built from 1D Dy(III) chains and copper iodide clusters [Cu 4 I 3 ], generating into three-dimensional frameworks with an open 1D channel along the a axis. 1 and 2 display extensive and excellent solvent stability. Magnetic studies of 1 and 2 indicate that they exhibit interesting solvent-dependent magnetization dynamics. Importantly, 1 and 2 can act as highly effective catalysts for the carboxylic cyclization of propargyl alcohols with carbon dioxide (CO 2 ) under ambient operating conditions. Additionally, the substrate scope was further explored over compound 1 based on the optimal conditions, and it exhibits efficient cyclic carboxylation of various terminal propargylic alcohols with CO 2 . This research offers an effective approach for the solvent-guided synthesis of MOFs materials and also presents the great application value of MOFs in CO 2 chemical conversion.

Objective: To delineate temporal and spatial dynamics of vascular smooth muscle cell (SMC) transcriptomic changes during aortic aneurysm development in Marfan syndrome (MFS). Approach and Results: We performed single-cell RNA sequencing to study aortic root/ascending aneurysm tissue from Fbn1 C1041G/ + (MFS) mice and healthy controls, identifying all aortic cell types. A distinct cluster of transcriptomically modulated SMCs (modSMCs) was identified in adult Fbn1 C1041G/ + mouse aortic aneurysm tissue only. Comparison with atherosclerotic aortic data (ApoE -/- mice) revealed similar patterns of SMC modulation but identified an MFS-specific gene signature, including plasminogen activator inhibitor-1 ( Serpine1 ) and Kruppel-like factor 4 ( Klf4 ). We identified 481 differentially expressed genes between modSMC and SMC subsets; functional annotation highlighted extracellular matrix modulation, collagen synthesis, adhesion, and proliferation. Pseudotime trajectory analysis of Fbn1 C1041G/ + SMC/modSMC transcriptomes identified genes activated differentially throughout the course of phenotype modulation. While modSMCs were not present in young Fbn1 C1041G/ + mouse aortas despite small aortic aneurysm, multiple early modSMCs marker genes were enriched, suggesting activation of phenotype modulation. modSMCs were not found in nondilated adult Fbn1 C1041G/ + descending thoracic aortas. Single-cell RNA sequencing from human MFS aortic root aneurysm tissue confirmed analogous SMC modulation in clinical disease. Enhanced expression of TGF-β (transforming growth factor beta)-responsive genes correlated with SMC modulation in mouse and human data sets., Conclusions: Dynamic SMC phenotype modulation promotes extracellular matrix substrate modulation and aortic aneurysm progression in MFS. We characterize the disease-specific signature of modSMCs and provide temporal, transcriptomic context to the current understanding of the role TGF-β plays in MFS aortopathy. Collectively, single-cell RNA sequencing implicates TGF-β signaling and Klf4 overexpression as potential upstream drivers of SMC modulation.

Alzheimer's disease (AD) is the most prevalent form of dementia, accounting for 60-70% of all dementias. AD is often under-diagnosed and recognized only at a later, more advanced stage, and this delay in diagnosis has been suggested as a contributing factor in the numerous unsuccessful AD treatment trials. Although there is no known cure for AD, early diagnosis is important for disease management and care. A hallmark of AD is the deposition of amyloid-β (Aβ)-containing senile neuritic plaques and neurofibrillary tangles composed of hyperphosporylated tau in the brain. However, current in vivo methods to quantify Aβ in the brain are invasive, requiring radioactive tracers and positron emission tomography. Toward development of alternative methods to assess AD progression, we focus on the retinal manifestation of AD pathology. The retina is an extension of the central nervous system uniquely accessible to light-based, non-invasive ophthalmic imaging. However, earlier studies in human retina indicate that the literature is divided on the presence of Aβ in the AD retina. To help resolve this disparity, this study assessed retinal tissues from neuropathologically confirmed AD cases to determine the regional distribution of Aβ in retinal wholemounts and to inform on future retinal image studies targeting Aβ. Concurrent post-mortem brain tissues were also collected. Neuropathological cortical assessments including neuritic plaque (NP) scores and cerebral amyloid angiopathy (CAA) were correlated with retinal Aβ using immunohistochemistry, confocal microscopy, and quantitative image analysis. Aβ load was compared between AD and control (non-AD) eyes. Our results indicate that levels of intracellular and extracellular Aβ retinal deposits were significantly higher in AD than controls. Mid-peripheral Aβ levels were greater than central retina in both AD and control eyes. In AD retina, higher intracellular Aβ was associated with lower NP score, while higher extracellular Aβ was associated with higher CAA score. Our data support the feasibility of using the retinal tissue to assess ocular Aβ as a surrogate measure of Aβ in the brain of individuals with AD. Specifically, mid-peripheral retina possesses more Aβ deposition than central retina, and thus may be the optimal location for future in vivo ocular imaging., (Copyright © 2020 Lee, Jiang, McIlmoyle, To, Xu, Hirsch-Reinshagen, Mackenzie, Hsiung, Eadie, Sarunic, Beg, Cui and Matsubara.)

Background: This study profiled the somatic genes mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA (ctDNA) from patients with neoplastic meningitis (NM)., Methods: A total of 62 CSF ctDNA samples were collected from 58 NM patients for the next generation sequencing. The data were bioinformatically analyzed by (Database for Annotation, Visualization and Integrated Discovery) DAVID software., Results: The most common mutated gene was TP53 (54/62; 87.10%), followed by EGFR (44/62; 70.97%), PTEN (39/62; 62.90%), CDKN2A (32/62; 51.61%), APC (27/62: 43.55%), TET2 (27/62; 43.55%), GNAQ (18/62; 29.03%), NOTCH1 (17/62; 27.42%), VHL (17/62; 27.42%), FLT3 (16/62; 25.81%), PTCH1 (15/62; 24.19%), BRCA2 (13/62; 20.97%), KDR (10/62; 16.13%), KIT (9/62; 14.52%), MLH1 (9/62; 14.52%), ATM (8/62; 12.90%), CBL (8/62; 12.90%), and DNMT3A (7/62; 11.29%). The mutated genes were enriched in the PI3K-Akt signaling pathway by the KEGG pathway analysis. Furthermore, the CNVs of these genes were also identified in these 62 samples. The mutated genes in CSF samples receiving intrathecal chemotherapy and systemic therapy were enriched in the ERK1/2 signaling pathway., Conclusions: This study identified genes mutations in all CSF ctDNA samples, indicating that these mutated genes may be acted as a kind of biomarker for diagnosis of NM, and these mutated genes may affect meningeal metastasis through PI3K-Akt signaling pathway.

Objective: To understand the epidemiological characteristics and risk factors of fatal cases of hand, foot, and mouth disease (HFMD) in children under 5 years old in China from 2008 to 2018, and provide evidence for the development of targeted prevention and control measures and reduction of the incidence of fatal HFMD cases. Methods: The incidence data of reported HFMD cases in China during 2008-2018 were collected from the National Notifiable Disease Surveillance Reporting System of China for the analyses on the demographic characteristics, spatial distribution, diagnosis or reporting and pathogen spectrum of the HFMD cases. Then the risk factors causing deaths were analyzed by using logistic regression model. Results: From 2008 to 2018, a total of 3 646 fatal cases of HFMD in children under 5 years old were reported in China. There were more fatal HFMD cases in boys than in girls (1.82∶1), the death mainly occurred in age group 0 to 2 years (87.71%). Adjusted mortality rate of HFMD in children under 5 years old in China declined from 0.87 per 100 000 in 2010 to 0.11 per 100 000 in 2018 (APC=-23.20%). In the 2 523 laboratory-confirmed deaths, 2 323 (92.07%) were EV-A71 infections, but the constituents of CV-A16 and other enterovirus infections increased. The interval from onset to diagnosis M =2( P (25) -P (75):2 - 4)d. The interval from onset to death M =3( P (25) -P (75):2 - 4)d. Age between 0 and 1 years, EV-A71 infection, longer interval between onset and diagnosis, and living in rural area were the risk factors causing fatal HFMD cases. Conclusions: The number of the fatal cases, the rate of mortality and case fatality HFMD in China had shown downward trends since 2010. EV-A71 is still the main pathogen causing fatal cases, but we should pay more attention to gene pattern of the other enteroviruses except EV-A71 and CV-A16. To reduce the risk of the fatal cases we should strengthen the health education about the immunization of EV-A71 inactivated vaccines and reduce the interval from onset to diagnosis in young children in western provinces and rural areas.

Objective: To evaluate the incidence intensity of hand, foot, and mouth disease (HFMD) in 2018/2019 season in southern China by Moving Epidemic Method (MEM), and compare the intensity among provinces, so as to provide basis for optimizing the allocation of public health resources. Methods: The weekly incidence data of HFMD of children under 5 years old in 15 provinces of southern China from March 1, 2012 to February 28, 2019 were collected from Disease Surveillance Reporting System of Chinese Center for Disease Control and Prevention, and the epidemic intensity threshold of each province in southern China during this period was calculated and evaluated by MEM. Results: In the first incidence peak of 2018/2019 HFMD season, in 15 provinces in the south China, 6 provinces (Jiangsu, Zhejiang, Jiangxi, Chongqing, Sichuan and Yunnan) reported very high incidence rates in children under 5 years old while Guangdong, Guangxi and Hainan provinces had low incidence level. In the second incidence peak, the incidences in 6 provinces (Shanghai, Jiangsu, Zhejiang, Chongqing, Sichuan and Yunnan) reached very high levels. The incidences in remaining provinces also reached medium or high levels. In most provinces, the thresholds in the first incidence peak were higher than those in the second incidence peak, but Chongqing and Sichuan were different. The results of model validation showed that the sensitivity and specificity of MEM were higher than 70% except for Hainan, Chongqing and Yunnan. Conclusions: For southern provinces with two incidence peaks in HFMD season, MEM can be used to determine the epidemic intensity thresholds of different incidence peaks by dividing the disease season to analyze the incidence intensity of HFMD in different stages. The epidemic intensity threshold established by MEM integrates the historical data, and the province (city) with extremely high epidemic level identified represents that the province (city) has an abnormal increase compared with the historical incidence level, which requires more attention from all areas and timely implementation of prevention and control measures.

Acute spontaneous intracerebral hemorrhage (ICH) is a life-threatening disease. It is often accompanied by severe neurological sequelae largely caused by the loss of integrity of the neural circuits. However, these neurological sequelae have few strong medical interventions. Designer receptors exclusively activated by designer drugs (DREADDs) are important chemogenetic tools capable of precisely modulating the activity of neural circuits. They have been suggested to have therapeutic effects on multiple neurological diseases. Despite this, no empirical research has explored the effects of DREADDs on functional recovery after ICH. We aimed to explore whether the long-term excitation of glutamatergic neurons in primary motor cortex (M1) by DREADD could promote functional recovery after ICH. We used CaMKII-driven Gq/Gi-DREADDs to activate/inhibit M1 glutamatergic neurons for 21 consecutive days, and examined their effects on behavioral and cognitive deficits caused by ICH in a mouse model of ICH targeting striatum. Long-term chemogenetic activation of the M1 glutamatergic neurons increased the spatial memory and sensorimotor ability of mice suffering from ICH. It also attenuated the mitochondrial dysfunctions of striatal neurons by raising the ATP levels and mitochondrial membrane potential while decreasing the 8-OHdG levels. These results strongly suggest that selective stimulation of the M1 glutamatergic neurons contributes to functional recovery after ICH presumably through alleviation of mitochondrial dysfunctions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To analyze the epidemiological characteristics of outbreaks of dengue fever in China from 2015 to 2018, and provide evidence for the prevention and control of dengue fever. Methods: We extracted the incidence data of dengue fever from China Disease Prevention and Control Information System, Public Health Emergency Reporting Management Information System and Vector Biological Monitoring System, and explored the epidemiological characteristics of the outbreaks in the past four years. Excel 2010 software and SPSS 20.0 software were used for data processing and analysis, ArcGIS 10.5 software was used for mapping. Results: A total of 111 outbreaks of dengue fever were reported nationwide from 2015 to 2018, involving 12 490 cases, accounting for 73.7% of the total cases in China. These outbreaks occurred in 85 counties and districts of 4 provinces, namely Guangdong (77 outbreaks), Yunnan (14 outbreaks), Zhejiang (8 outbreaks) and Fujian (8 outbreaks). The outbreaks occurred during May-November. Small-scale outbreaks with no more than 10 cases ended within 30 days (28/34, 82.4%) and larger-scale outbreaks lasted for several months. Dengue virus type 1 and type 2 were the main epidemic pathogens of dengue fever outbreaks in China. The outbreaks mainly occurred in areas with high population density and poor sanitary environment. There were significant differences in the age and occupational composition of the cases in the main outbreak provinces. Conclusions: Outbreaks of dengue fever can been seen in more areas in China, even in high latitudes areas. The epidemiologic characteristics of the outbreaks were different among provinces, showing as port type, rural type and urban type. Each province should adjust the control strategies accordingly.

Marfan syndrome (MFS) is a connective tissue disorder that results in aortic root widening and aneurysm if unmanaged. We have previously reported doxycycline, a nonselective matrix metalloproteinases (MMPs) inhibitor, to attenuate aortic root widening and improve aortic contractility and elasticity in MFS mice. We were also first to use multiphoton microscopy, a non-invasive and label-free imaging technique, to quantify and link the aortic ultrastructure to possible changes in the skin dermis. Here, we aimed to assess the effects of long-term doxycycline treatment on the aortic ultrastructure and skin dermis of MFS mice through immunohistochemical evaluation and quantification of elastic and collagen content and morphology using multiphoton microscopy. Our results demonstrate a rescue of aortic elastic fiber fragmentation and disorganization accompanied by a decrease in MMP-2 and MMP-9 expression within the aortic wall in doxycycline-treated MFS mice. At 12 months of age, reduced skin dermal thickness was observed in both MFS and control mice, but only dermal thinning in MFS mice was rescued by doxycycline treatment. MMP-2 and MMP-9 expression was reduced in the skin of doxycycline-treated MFS mice. A decrease in dermal thickness was found to be positively associated with increased aortic root elastin disorganization and wall thickness. Our findings confirm the beneficial effects of doxycycline on ultrastructural properties of aortic root as well as on skin elasticity and structural integrity in MFS mice.

Granzymes are a family of serine proteases first shown to be intracellular initiators of immune-mediated cell death in target pathogenic cells. In addition to its intracellular role, Granzyme B (GzmB) has important extracellular functions in immune regulation and extracellular matrix (ECM) degradation. Verified substrates of extracellular GzmB activity include tight junctional and ECM proteins. Interestingly, little is known about the activity of GzmB in the outer human retina, a tissue in which the degradation of the tight junctional contacts of retinal pigment epithelial (RPE) cells and within the external limiting membrane, as well as remodeling of the ECM in Bruch's membrane, cause the breakdown of the blood-retinal barrier and slowing of metabolite transport between neuroretina and choroidal blood supply. Such pathological changes in outer retina signal early events in the development of age-related macular degeneration (AMD), a multifactorial, chronic inflammatory eye disease. This study is the first to focus on the distribution of GzmB in the outer retina of the healthy and diseased post-mortem human eye. Our results revealed that GzmB is present in RPE and choroidal mast cells. More immunoreactive cells are present in older (>65 years) compared to younger (<55 years) donor eyes, and choroidal immunoreactive cells are more numerous in eyes with choroidal neovascularization (CNV), while RPE immunoreactive cells are more numerous in eyes with soft drusen, an early AMD event. In vitro studies demonstrated that RPE-derived tight junctional and ECM proteins are cleaved by exogenous GzmB stimulation. These results suggest that the increased presence of GzmB immunoreactive cells in outer retina of older (healthy) eyes as well as in diseased eyes with CNV (from AMD) and eyes with soft drusen exacerbate ECM remodeling in the Bruch's membrane and degradation of the blood-retinal barrier. Currently there are no treatments that prevent remodeling of the Bruch's membrane and/or the loss of function of the outer blood-retinal barrier, known to promote early AMD changes, such as drusen deposition, RPE dysfunction and pro-inflammation. Specific inhibitors of GzmB, already in preclinical studies for non-ocular diseases, may provide new strategies to stop these early events associated with the development of AMD., (Copyright © 2020 Matsubara, Tian, Cui, Zeglinski, Hiroyasu, Turner and Granville.)

A family of new dinuclear lanthanide complexes as the simplest entities showing intramolecular magnetic interactions, [Ln2(dbm)2(L)2(CH3OH)2] (Ln = Tb (1), Dy (2), Ho (3), Er (4), Yb (5), Lu (6)), [Ln2(acac)2(L)2(EtOH)2] (Ln = Dy (7), Er (8)), [Dy2(TTA)2(L)2(CH3OH)2]·2CH2Cl2 (9) and [Dy2(tfa)2(L)2(CH3OH)2] (10) (H2L = N'-(2-hydroxy-5-methylphenyl)-pyrazine-2-carbohydrazide, Hdbm = 1,3-diphenyl-1,3-propanedione, Hacac = acetylacetone, HTTA = 2-thenoyltrifluoroacetone, Htfa = trifluoroacetylacetone), were constructed successfully by the reaction of a Schiff base ligand H2L and four different β-diketonate salts. As for complexes 4, 5 and 8, all exhibit the characteristic emission peaks of the corresponding Er3+, Yb3+ and Er3+ ions, respectively. Meanwhile, the excitation wavelength (510 nm) of 5 is located in the visible region, confirming its significant potential application value. Magnetic studies indicate that complexes 9 and 10 exhibit characteristic slow relaxation of magnetization with the energy barriers (Ueff) of 102 K for 9 and 140 K for 10 under a zero dc field. Under the optimized dc fields, slow magnetic relaxations are present in 2 and 7, and the Ueff values of 9 and 10 have been improved. This proves that the β-diketonate co-ligands deserve an important role in regulating Dy-SMMs influenced by the diverse perturbations of the axial crystal field originating from minor changes in the coordination environment.

Aortic root aneurysm formation is a cardinal feature of Marfan syndrome (MFS) and likely TGF-β driven via Smad (canonical) and ERK (non-canonical) signalling. The current study assesses human MFS vascular smooth muscle cell (SMC) phenotype, focusing on individual contributions by Smad and ERK, with Notch3 signalling identified as a novel compensatory mechanism against TGF-β-driven pathology. Although significant ERK activation and mixed contractile gene expression patterns were observed by traditional analysis, this did not directly correlate with the anatomic site of the aneurysm. Smooth muscle cell phenotypic changes were TGF-β-dependent and opposed by ERK in vitro, implicating the canonical Smad pathway. Bulk SMC RNA sequencing after ERK inhibition showed that ERK modulates cell proliferation, apoptosis, inflammation, and Notch signalling via Notch3 in MFS. Reversing Notch3 overexpression with siRNA demonstrated that Notch3 promotes several protective remodelling pathways, including increased SMC proliferation, decreased apoptosis and reduced matrix metalloproteinase activity, in vitro. In conclusion, in human MFS aortic SMCs: (a) ERK activation is enhanced but not specific to the site of aneurysm formation; (b) ERK opposes TGF-β-dependent negative effects on SMC phenotype; (c) multiple distinct SMC subtypes contribute to a 'mixed' contractile-synthetic phenotype in MFS aortic aneurysm; and (d) ERK drives Notch3 overexpression, a potential pathway for tissue remodelling in response to aneurysm formation., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Fluid and charge transport in micro- and nanoscale fluidic systems are intrinsically coupled via electrokinetic phenomena. While electroosmotic flows and streaming potentials are well understood for externally imposed stimuli, charge injection at electrodes localized inside fluidic systems via electrochemical processes remains to a large degree unexplored. Here, we employ ultramicroelectrodes and nanogap electrodes to study the subtle interplay between ohmic drops, streaming currents, and faradaic processes in miniaturized channels at low concentrations of supporting electrolyte. We show that electroosmosis can, under favorable circumstances, counteract the effect of ohmic losses and shift the apparent formal potential of redox reactions. This interplay can be described by simple circuit models, such that the results described here can be adapted to other micro- and nanofluidic electrochemical systems., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Background: Meningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical manifestation, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging features. However, negative rate of CSF cytology and neuroimaging findings often result in a failure to diagnose MC from the patients who actually have the disease. Here we evaluate the CSF circulating tumor DNA (ctDNA) in the diagnosis of MC., Methods: A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF ctDNA extraction and cancer-associated gene mutations detection by next-generation sequencing (NGS) at the same time., Results: The most frequent primary tumor in this study was lung cancer (26/35, 74%), followed by gastric cancer (2/35, 6%), breast cancer (2/35, 6%), prostatic cancer (1/35, 3%), parotid gland carcinoma (1/35, 3%) and lymphoma (1/35, 3%) while no primary tumor could be found in the remaining 2 patients in spite of using various inspection methods. Twenty-five CSF samples (25/35; 71%) were found neoplastic cells in CSF cytology examination while all of the 35 CSF samples (35/35; 100%) were revealed having detectable ctDNA in which cancer-associated gene mutations were detected. All of 35 patients with MC in the study underwent contrast-enhanced brain MRI and/or CT and 22 neuroimaging features (22/35; 63%) were consistent with MC. The sensitivity of the neuroimaging was 88% (95% confidence intervals [95% CI], 75 to 100) (p = 22/25) and 63% (95% CI, 47 to 79) (p = 22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71% (95% CI, 56 to 86) (n = 25/35) compared to that of CSF ctDNA., Conclusions: This study suggests a higher sensitivity of CSF ctDNA than those of CSF cytology and neuroimaging findings. We find cancer-associated gene mutations in ctDNA from CSF of patients with MC at 100% of our cohort, and utilizing CSF ctDNA as liquid biopsy technology based on the detection of cancer-associated gene mutations may give additional information to diagnose MC with negative CSF cytology and/or negative neuroimaging findings.

Herein, ten new linear-shaped LnIII4 and LnIII6 clusters, with the formula [Ln4(acac)6L2(CH3O)2(CH3OH)4]·xCH3OH (Ln = Nd (1), Sm (2), Eu (3), Gd (4), Tb (5), Dy (6), and Tm (8), Hacac = acetylacetone), [Ln6(acac)4L4(CH3O)6]·xCH3OH (Er (7) and Yb (9)), and [Lu4(acac)6L2(OH)2]·2CH2Cl2 (10), based on a polydentate Schiff base ligand, H2L, and a β-diketone co-ligand were successfully synthesized and structurally characterized. Single crystal X-ray diffraction measurements reveal that the structures of the clusters 1-6, 8 and 10 are very similar and their central Ln(iii) ions are linearly arranged Ln4; however, the clusters 7 and 9 possess a rare linearly arranged Ln6. The investigations on the solid-state fluorescence properties show that the clusters 2, 3, 5 and 6 display the characteristic lanthanum luminescence at room temperature. Magnetic studies reveal that weak antiferromagnetic interactions exist between adjacent Gd(iii) ions in cluster 4. More importantly, the cluster 4 exhibits significant MCE with the maximum -ΔSm value of 27.96 J kg-1 K-1 at 2.0 K and 7.0 T, whereas the cluster 6 displays a slow magnetic relaxation behavior under a zero dc field with the effective energy barrier ΔE/kB = 8.64 K and τ0 = 6.98 × 10-6 s.

Objectives: To understand the status of studies about influenza economic burden in mainland China and summarize their major results. Methods: The words of influenza, flu, cost, economic, burden, effectiveness, benefit, utility, China, and Chinese, were used as search keywords. Journal papers published during 2000-2018 were searched from Chinese electronic databases (CNKI and Wanfang) and English electronic databases (PubMed, Web of science, EconLit and Cochrane Library). The language of literature was restricted to Chinese and English. A total of 23 effective documents were included, and the descriptive characteristics, research indexes and methods included in the literature were analyzed. The monetary unit used in this review is Chinese Yuan (CNY). Results: The 23 study sites were mainly in the relatively developed and populous regions. The total cost per capita of laboratory-confirmed influenza,of all age-group was reported in 6 literatures, and only 4 literatures reported it in out-patients (range: 768.0-999.9 CNY), Only one study reported this indicator in inpatients (9 832.0 CNY). One literature reported the total cost per capita of influenza-like illness,, which was 205.1 CNY. And one literature reported that the direct medical cost of inpatients per capita in children under 5 years of age was 6 072.0 CNY while two literature reported this index for the elderly over 60 years of age, ranging from 14 250.0 to 19 349.1 CNY. Four articles reported the economic burden of influenza in urban and rural areas, one of which showed that the related expenses of urban influenza inpatients accounted for 31% of the average annual income, while which for the rural flow was 113%. Conclusion: The average economic burden of lab-confirmed influenza case is higher than that of influenza-like illness, and there are differences in outpatient indirect expenses and inpatients direct medical expenses. The direct medical burden for the hospitalized 60-years-and-beyond influenza case group is heavier thar other age group. By region, the influenza associated individual economic burden in rural area is higher than that of urban area..

Objective: To systematically review the mortality burden study of influenza in mainland China. Method: "influenza", "flu", "H1N1", "pandemic", "mortality", "death", "fatality", "burden", "China" and "Chinese" were used as keywords, and a systematic literature search was conducted to identify articles in three English databases (PubMed, Web of Science and Embase) and three Chinese database (CNKI, WanFang and VIP) during 1990-2018 (excluding Hong Kong, Macao and Taiwan). The language of literature was restricted to Chinese and English. The inclusion criteria were human-oriented researches with method based on population, and research indexes included mortality and excess mortality. The exclusion criteria were non-primary research materials, predictive research and research on the burden of avian influenza related deaths. A total of 17 literatures were included, and the basic information to descriptive characteristics, methodology of modeling and the corresponding results were extracted. Results: All the 17 studies adopted indirect statistical models, with 14 of which adopted the regression model, and all the research index was excess mortality. All causes (16 studies), respiratory and circulatory diseases (14 studies) and pneumonia and influenza (10 studies) were the main causes of death associated with influenza. Influenza associated mortality burden in the elderly was higher, with the lowest excess mortality rates of all causes, respiratory and circulatory diseases, pneumonia and influenza being 49.57, 30.80 and 0.69 per 100 000 people, and the highest rates being 228.16, 170.20 and 30.35 per 100 000 people, respectively. In the non-elderly, the corresponding lowest rates were -0.27, -0.08 and 0.04 per 100 000 people respectively, and the highest rates were 3.63, 2.6 and 0.91 per 100 000 people, respectively. The influenza-related excess mortality was higher in the north, with a minimum of 7.8 per 100 000 and a maximum of 18.0 per 100 000, and slightly lower in the south, with a minimum of 6.11 per 100 000 and a maximum of 18.7 per 100 000. There were also differences in deaths caused by different influenza virus subtypes, with influenza A(H3N2) and influenza B virus possibly posing a heavier mortality burden. Conclusions: Studies on influenza mortality burden is mainly based on indirect model and urban level in China. The mortality burden of influenza in the elderly, the northern and subtype A(H3N2) and B were more severe.

Background: Age-related macular degeneration (AMD) is a multifactorial chronic disease of the eye. Several candidate pathways have been hypothesized to play a role in AMD pathogenesis. Our work and those of others suggests inflammasome activity as a mechanism associated with retinal pigment epithelial (RPE) cell demise. X-linked inhibitor of apoptosis protein (XIAP), an anti-apoptosis factor, has recently been shown to regulate inflammasome activity in non-ocular cells. The purpose of this study is to characterize XIAP's regulatory role in RPE., Methods: Protein lysates of eye tissues from rats (vinpocetine- or aurin tricarboxylic acid complex-treated, ATAC, vs naïve) and mice (wild type vs Caspase-4 -/- ) were utilized to analyze XIAP protein levels. Immunohistochemistry was used to detect NLRP3 levels in the RPE layer. In vitro inflammasome activation on RPE cells was achieved with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) stimulation. Levels of XIAP mRNA and 18S RNA were quantified by RT-PCR. Cell culture supernatants were tested directly for secreted IL-1β by ELISA or concentrated for the detection of secreted IL-18 by western blot. Protein lysates from RPE in cell culture were collected for the measurement of cleaved caspase-1 p20, XIAP, and GAPDH. Data are presented as Mean ± SD. p < 0.05 is considered statistically significant., Results: The XIAP protein level was significantly increased when the inflammasome was inhibited at the "activation" step by ATAC, but not the "priming" step, in vivo. Concomitantly, NLRP3 immunoreactivity was lower in the RPE layer of animals fed with ATAC. In mice where caspase-1 cleavage was impaired by the genetic deficiency in caspase-4, the XIAP protein level increased in eye tissues. In RPE cell culture, Leu-Leu-OMe stimulation led to caspase-1 cleavage, cytokine secretion, and XIAP reduction, which can be abolished by Z-YVAD-FMK. When XIAP siRNA was given as a pre-treatment to RPE in vitro, Leu-Leu-OMe induced IL-1β/IL-18 secretion was enhanced, whereas overexpressing XIAP reduced IL-1β secretion under inflammasome activation, both compared to controls cells., Conclusions: Together, these data suggest XIAP-mediated inhibition of inflammasome activity in RPE may provide insights into the biological consequences of inflammasome activation in RPE and reveals the caspase-1/XIAP/IL-1β/IL-18 axis as a target for broader applications in AMD biology and treatment design.

Molecular logic gates play an important role in many fields and DNA-based logic gates are the basis of DNA computers. A dynamically NAND gate system on the DNA origami template is established in this paper. Naturally, the system is stable in solution without any reaction. Different logical values are mapped into different DNA input strands. When logical values are entered into the system, the corresponding DNA input strands undergo a directed hybridization chain reaction (HCR) at corresponding positions on the DNA origami template. The operation results are identified by disassembly between the nanogold particles (AuNPs) and DNA origami template. The nanogold particles remain on the DNA origami template, indicating that the result is true; The nanogold particles are dynamically separated from the DNA origami template, indicating that the result is false. The simulation of the system through Visual DSD shows that the reaction strictly followed the designed direction, and no error products are generated during the reaction. These simulation results show that the system has the advantages of feasibility, stability and intelligence., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: To investigate the alterations in both structure and contractile responsiveness of ocular ciliary artery (OCA) in spontaneously hypertensive rat (SHR)., Methods: In this experiment, 20-week-old male SHR and Wistar Kyoto rat (WKY) were studied. The heart rate (HR), the blood pressure (BP; the systolic BP and the diastolic BP) of rats with an electronic sphygmomanometer were measured. Vascular morphometry and isometric tension measurement were used to investigate the alterations in structure and contractility of OCA., Results: A general narrowing of OCAs was observed in SHR compared to the control WYK. In SHR, the media of OCAs were thicker, the luminal diameters were smaller, and the media-to-lumen ratios were higher when compared with WKY ( P <0.05). The contractions of OCAs evoked by norepinephrine were smaller in SHR compared to control ( P <0.05). Then, OCAs were pretreated with iberiotoxin, L-NAME, or indomethacin 30min before norepinephrine-induced contraction. Iberiotoxin (0.1 µmol/L) has not changed the norepinephrine-induced contractions in OCAs from both groups. However, L-NAME (100 µmol/L) increased the vasoconstrictions, the increased extents were similar in SHR and WKY ( P >0.05). Indomethacin (10 µmol/L) decreased the contractions induced by norepinephrine in OCAs from WKY ( P <0.05), but did not change those contractions in vessels from SHR ( P >0.05)., Conclusion: Our results demonstrate that the structure and function of OCAs are altered in hypertension. OCAs from SHR are remodeled with decreased lumen diameter and increased media-to-lumen ratio. Moreover, the contractile responsiveness of OCAs from SHR is diminished due to the disruption of vasoconstrictive effect of prostaglandins.

A novel 3D metal-organic framework (MOF){[Tb 3 (CBA) 2 (HCOO)(μ 3 -OH) 4 (H 2 O)]·2H 2 O·0.5DMF} n (S-1) was synthesized by the solvothermal method. The crystal structure indicates that [Tb 4 O 4 ] cubane clusters self-assemble into an infinite chain by sharing vertex, which is further linked to adjacent chains through 1,1-cyclobutanedicarboxylic acid ligand (H 2 CBA), resulting in a honeycomb arrayed framework. S-1 possesses excellent water stability and still retains intact structure after exposure to water for 10 weeks or boiling water for 10 weeks. Interestingly, S-1 acts as a luminescence sensor to selectively and sensitively detect quercetin with the limit of detection (LOD) as low as 0.23 ppm (7.6 × 10 -7 M). The relationship between relative luminescence intensity and concentration obeys linear in the range of 0-300 ppm (0-993 μM), which allows quantitative detection of quercetin. Importantly, S-1 can be reused at least six times with almost no change in luminescent intensity. Compared with the high performance liquid chromatography-mass spectrometry (HPLC-MS) method, S-1 was used to determine the content of quercetin in onionskin and apple peel samples with satisfactory results. Furthermore, a portable S-1 test paper is also developed and expected to be applied in practice. To our knowledge, S-1 is the first example of MOFs as luminescent sensor for quercetin.

Aortic aneurysm is the most life-threatening complication in Marfan syndrome (MFS) patients. Doxycycline, a nonselective matrix metalloproteinases inhibitor, was reported to improve the contractile function and elastic fiber structure and organization in a Marfan mouse aorta using ex vivo small chamber myography. In this study, we assessed the hypothesis that a long-term treatment with doxycycline would reduce aortic root growth, improve aortic wall elasticity as measured by pulse wave velocity, and improve the ultrastructure of elastic fiber in the mouse model of MFS. In our study, longitudinal measurements of aortic root diameters using high-resolution ultrasound imaging display significantly decreased aortic root diameters and lower pulse wave velocity in doxycycline-treated Marfan mice starting at 6 months as compared to their non-treated MFS counterparts. In addition, at the ultrastructural level, our data show that long-term doxycycline treatment corrects the irregularities of elastic fibers within the aortic wall of Marfan mice to the levels similar to those observed in control subjects. Our findings underscore the key role of matrix metalloproteinases during the progression of aortic aneurysm, and provide new insights into the potential therapeutic value of doxycycline in blocking MFS-associated aortic aneurysm.

Six phenoxo-O bridged dinuclear lanthanide(iii) complexes have been assembled utilizing the 2-[(4-nitrophenyl)imino]methyl-8-hydroxyquinoline (HL) and dibenzoylmethane (Hdbm) ligands: [Ln2(dbm)4L2] (Ln = Nd (1), Eu (2), Gd (3), Tb (4), Dy (5) and Er (6)). Complexes 1 and 6 exhibit the characteristic emission peaks of the corresponding Nd3+ and Er3+ ions, respectively. Meanwhile, the excitation wavelength (470 nm) for complex 1 is located in the visible-light region, confirming a practical application value. The studies on magnetic properties reveal that complex 3 features a magnetocaloric effect with a magnetic entropy change of -ΔSm = 14.36 J kg-1 K-1 at 4 K for ΔH = 7 T. What's more, the dynamic magnetic studies for complex 5 show that it exhibits slow magnetic relaxation behavior, typical of SMM behavior, resulting in an energy barrier of ΔE/kB = 75 K with the pre-exponential factor τ0 = 2.2 × 10-7 s. Meanwhile, this research demonstrates that the magnetic properties can be modulated by regulating the electron-donating/withdrawing effects of the substituents on the ligands.

Objective: To evaluate the clinical value and outcomes of technical improvement of hybrid operatical clipping for large paraclinoid internal carotid artery aneurysms. Methods: A review was conducted on 18 cases of large paraclinoid internal carotid artery aneurysm which were clipped by balloon non-fluoroscopic occlusion of the parent artery via a micro-bone window frontolateral approach in hybrid operating room at Neurosurgery Department of Tianjin Medical University General Hospital from June 2014 to December 2017. There were 8 males and 10 females with age of (63±4) years. There were 6 cases of unruptured aneurysm and 12 cases of ruptured aneurysm of subarachnoid hemorrhage (6 cases of grade Ⅱ, 4 cases of grade Ⅲ and 2 cases of grade Ⅳ in Hunt-Hess classification). Frontolateral approach incision (average length of about 5 cm) and bone window about 3 cm×3 cm were performed. No incision of the neck was needed to expose the internal carotid artery for temporary occlusion. In the operation, the balloon was slowly pushed to the preset position of the internal carotid artery under non-fluoroscopy. The balloon was expanded to block the blood flow of internal carotid artery. Then aneurysm was clipped. The balloon was loosened and retraced to the guiding catheter after clipping. The clipping condition was examined by cerebral angiography. If there was residual aneurysm neck or stenosis of the parent artery, the balloon was pushed under non-fluoroscopy again to temporary occlusion and the clip was adjusted until the aneurysm neck was clamped satisfactorily. Results: Eighteen aneurysms were successfully clipped in hybrid operating room. Fourteen aneurysms showed complete occlusion of the aneurysm neck and no stenosis of the parent artery. Four cases showed residual aneurysm neck after clipping by intraoperative angiography, then aneurysms were clipped satisfy by adjusting the aneurysm clip. The patients were followed up for 3 months to 1 year. Ten patients recovered well (modifed Rankin score (mRS): 0), and 3 patients had no obvious disability (mRS: 1). Two patients with Hunt-Hess grade Ⅲ were slightly disabled (mRS: 2). 1 patients with Hunt-Hess grade Ⅲ were moderately disabled (mRS: 3). 1 patients with Hunt-Hess grade Ⅳ were severely disabled (mRS: 4). One elderly patients with Hunt-Hess grade Ⅳ were seriously disabled (mRS: 5). Conclusions: Application of balloon non-fluoroscopic occlusion clipping for large paraclinoid internal carotid artery aneurysm via a micro-bone window frontolateral approach is safe, effective and minimally invasive.