Circulating Autoantibody Profiling Identifies LIMS1 as a Potential Target for Pathogenic Autoimmunity in pathologic Myopia.

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.

Hybrid Membrane of Sulfonated Poly(aryl ether ketone sulfone) Modified by Molybdenum Clusters with Enhanced Proton Conductivity.

Developing novel proton exchange membranes (PEMs) with low cost and superior performance to replace Nafion is of great significance. Polyoxometalate-doped sulfonated poly(aryl ether ketone sulfone) (SPAEKS) allows for the amalgamation of the advantages in each constituent, thereby achieving an optimized performance for the hybrid PEMs. Herein, the hybrid membranes by introducing 2MeIm-{Mo132} into SPAEKS are obtained. Excellent hydrophilic properties of 2MeIm-{Mo132} can help more water molecules be retained in the hybrid membrane, providing abundant carriers for proton transport and proton hopping sites to build successive hydrophilic channels, thus lowering the energy barrier, accelerating the proton migration, and significantly fostering the proton conductivity of hybrid membranes. Especially, SP-2MIMo132-5 exhibits an enhanced proton conductivity of 75 mS cm-1 at 80 °C, which is 82.9% higher than pristine SPAEKS membrane. Additionally, this membrane is suitable for application in proton exchange membrane fuel cells, and a maximum power density of 266.2 mW cm-2 can be achieved at 80 °C, which far exceeds that of pristine SPAEKS membrane (54.6 mW cm-2). This work demonstrates that polyoxometalate-based clusters can serve as excellent proton conduction sites, opening up the choice of proton conduction carriers in hybrid membrane design and providing a novel idea to manufacture high-performance PEMs.

COMBINED APPLICATION OF B-SCAN ULTRASONOGRAPHY AND EYE-STEERING ULTRAWIDE FIELD IMAGING TO IMPROVE THE DETECTION OF RETINAL TEARS BEFORE CATARACT SURGERY.

PURPOSE: To investigate the efficacy of combined application of B-scan ultrasonography (US) and ultrawide field imaging (UWFI) in detecting retinal tears before cataract surgery. METHODS: Of 1,277 cataract patients, 2,552 eyes were enrolled and received both B-scan US and UWFI examinations preoperatively. Three types of combination were applied: type 1 (union, B-scan US or centered UWFI), type 2 (intersection, B-scan US and centered UWFI), and type 3 (B-scan US and eye-steering UWFI). Sensitivity and specificity of detecting retinal tears by different methods were assessed. RESULTS: Totally 4.55% (116/2,552) of eyes were presented with retinal tears. The sensitivity of B-scan US and UWFI was 87.93% and 84.48%, and specificity was 95.16% and 99.79%, respectively. By applying type 1 and type 2 combination, the sensitivity was 98.28% and 74.14%, and specificity was 95.03% and 99.92%, respectively. By type 3 combination, the sensitivity increased to 95.69% and specificity to 99.88%, both of which were comparable to indirect ophthalmoscopy regardless of the number, type, and location of tears ( P > 0.05). In eyes with any cataract type or axial length, type 3 combination also gained comparable performance to indirect ophthalmoscopy. CONCLUSION: Combined application of B-scan US and eye-steering UWFI presented satisfactory performance in detecting retinal tears before cataract surgery.

Regulating effect of miR-132-3p on the changes of MAPK pathway in rat brains and SH-SY5Y cells exposed to excessive fluoride by targeting expression of MAPK1.

BACKGROUND: Although the changes of mitogen-activated protein kinase (MAPK) pathway in the central nervous system (CNS) induced by excessive fluoride has been confirmed by our previous findings, the underlying mechanism(s) of the action remains unclear. Here, we investigate the possibility that microRNAs (miRNAs) are involved in the aspect. METHODS: As a model of chronic fluorosis, SD rats received different concentrations of fluoride in their drinking water for 3 or 6 months and SH-SY5Y cells were exposed to fluoride. Literature reviews and bioinformatics analyses were used to predict and real-time PCR to measure the expression of 12 miRNAs; an algorithm-based approach was applied to identify multiply potential target-genes and pathways; the dual-luciferase reporter system to detect the association of miR-132-3p with MAPK1; and fluorescence in situ hybridization to detect miR-132-3p localization. The miR-132-3p inhibitor or mimics or MAPK1 silencing RNA were transfected into cultured cells. Expression of protein components of the MAPK pathway was assessed by immunofluorescence or Western blotting. RESULTS: In the rat hippocampus exposed with high fluoride, ten miRNAs were down-regulated and two up-regulated. Among these, miR-132-3p expression was down-regulated to the greatest extent and MAPK1 level (selected from the 220 genes predicted) was corelated with the alteration of miR-132-3p. Furthermore, miR-132-3p level was declined, whereas the protein levels MAPK pathway components were increased in the rat brains and SH-SY5Y cells exposed to high fluoride. MiR-132-3p up-regulated MAPK1 by binding directly to its 3'-untranslated region. Obviously, miR-132-3p mimics or MAPK1 silencing RNA attenuated the elevated expressions of the proteins components of the MAPK pathway induced by fluorosis in SH-SY5Y cells, whereas an inhibitor of miR-132-3p just played the opposite effect. CONCLUSION: MiR-132-3p appears to modulate the changes of MAPK signaling pathway in the CNS associated with chronic fluorosis.

A fatal case of neonatal viral sepsis caused by human parainfluenza virus type 3.

BACKGROUND: Sepsis is a systemic inflammatory response syndrome caused by severe infection in children, but cases of sepsis associated with human parainfluenza virus (HPIV) have been rarely reported in newborns. CASE PRESENTATION: We report a case of HPIV-3 positive full-term newborn admitted to the Neonatal Intensive Care Unit of Beijing Children's Hospital due to hematuria, gloomy spirit, inactivity and loss of appetite for 6 h. He had septic shock when he arrived the Accident & Emergency Department requiring immediate intubation and mechanical ventilation. Intravenous antibiotics were started. He had completely negative response to all anti-shock treatments including fluid resuscitation and vasopressor supports, and died 14 h later. Viral nucleic acid detection and metagenomic next-generation sequencing (mNGS) analyses of nasopharyngeal aspirate and blood specimens verified an HPIV-3 infection, with negative bacterial culture results. The HPIV-3 strain detected in this patient was subtyped as HPIV C3a, and two unreported amino acid mutations were found in the HN protein region. CONCLUSION: The patient had a severe infection associated with HPIV-3, which was the cause of sepsis and septic shock. This study showed the diagnostic value of mNGS in etiological diagnosis, especially in severe neonatal case.

Impact on etiology diagnosis by high-resolution vessel wall imaging in young adults with ischemic stroke or transient ischemic attack.

PURPOSE: The etiological features of stroke in young adults are different from those in older adults. We aimed to investigate the impact of high-resolution vessel wall imaging (HRVWI) on etiologic diagnosis in young adults with ischemic stroke or transient ischemic attack (TIA). METHODS: A total of 253 young adults (aged 18-45 years) who consecutively underwent HRVWI for clarifying stroke etiology were retrospectively recruited. Two experienced neurologists classified stroke etiology for each patient using Trial of Org 10,172 in Acute Stroke Treatment categories with and without the inclusion of HRVWI diagnosis. Multivariate logistic regression was performed to determine which etiologic category would be significantly impacted after including HRVWI. RESULTS: The etiologic classification was altered in 39.1% (99/253) of patients after including HRVWI in the conventional investigations. The proportion of patients classified as having stroke of undetermined etiology (SUE) and the proportion of patients classified as having small-artery occlusion (SAO) both significantly decreased (36.4 to 13.8% and 9.1 to 2.0%), whereas the proportion of patients classified as having large artery atherosclerosis (LAA) significantly increased (28.5 to 58.1%) (all P < 0.001). The inclusion of HRVWI had a significant diagnostic impact on young adults who were primarily classified as SAO (odds ratio [OR] 14.4, 95% confidence interval [CI] [2.9, 71.8], P < 0.001) or SUE (OR 8.3, 95% CI [2.2, 31.5], P < 0.01). CONCLUSIONS: HRVWI had a substantial impact on etiologic classification in young adults with ischemic stroke or TIA, particularly for those primarily classified as having SAO or SUE. This impact of HRVWI will be beneficial for therapeutic decision-making.

Asteriquinones from Aspergillus sp. GZWMJZ-258 and Their Derivatives.

A new asteriquinone, ochrindole F (1), and five previously reported analogues (2-6) were isolated from the culture of the fungus Aspergillus sp. GZWMJZ-258, an endophyte of Garcinia multiflora. The structure of compound 1 was determined by a spectroscopic analysis. Furthermore, eight new derivatives (7-14) were synthesized from major metabolites 2 and 3. These compounds showed selective antiproliferative activity against the human acute myeloid leukemia (AML) cell line MV4-11, among which compound 12 showed the strongest activity with an IC50 value of 0.14 µM and the highest selectivity with a selectivity index greater than 710. An initial probe of the mechanism of action showed that compounds 12 and 14 could inhibit the expression of FLT-3 in the MV4-11 cell line.

LONG-TERM PROGRESSION PATTERN OF MYOPIC TRACTIONAL MACULOPATHY: Outcomes and Risk Factors.

PURPOSE: To evaluate the long-term progression pattern of myopic tractional maculopathy and the risk factors. METHODS: The prevalence and grade of myopic tractional maculopathy were assessed with optical coherence tomography at enrollment and at the 2-year follow-up. The severity of posterior staphyloma and the presence of dome-shaped macula were also evaluated. RESULTS: In total, 610 highly myopic eyes of 610 patients were analyzed. The prevalence of epiretinal membrane, myopic retinoschisis, and macular hole increased from 26.7%, 12.1%, and 4.4% at enrollment to 41.1%, 18.2%, and 9.5% at the 2-year follow-up, respectively. Epiretinal membrane progressed in 21.8% of eyes, but visual acuity did not decline significantly in these eyes. Myopic retinoschisis progressed in 6.8% of eyes, and macular hole progressed in 14.8% of eyes. Significantly greater best-corrected visual acuity reduction was detected in the eyes with myopic retinoschisis or macular hole progression than the rest ( P < 0.05). Multivariate analysis showed that longer axial length, more-severe posterior staphyloma, and absence of dome-shaped macula were associated with myopic tractional maculopathy progression. CONCLUSION: In highly myopic eyes, long-term visual acuity was relatively stable in those with epiretinal membrane, but was significantly affected by myopic retinoschisis or macular hole progression. Longer axial length, more-severe posterior staphyloma, and absence of dome-shaped macula were risk factors for myopic tractional maculopathy progression.

Prevalence and Characteristics of Adrenal Tumors in an Unselected Screening Population : A Cross-Sectional Study.

BACKGROUND: With the widespread use of advanced imaging technology, adrenal tumors are increasingly being identified. OBJECTIVE: To investigate the prevalence and characteristics of adrenal tumors in an unselected screening population in China. DESIGN: Cross-sectional study. (ClinicalTrials.gov: NCT04682938). SETTING: A health examination center in China. PATIENTS: Adults having an annual checkup were invited to be screened for adrenal tumors by adrenal computed tomography. MEASUREMENTS: The participants with adrenal tumors had further evaluation for malignancy risk and adrenal function. RESULTS: A total of 25 356 participants were screened, 351 of whom were found to have adrenal tumors, for a prevalence of 1.4%. The prevalence increased with age, from 0.2% in participants aged 18 to 25 years to 3.2% in those older than 65 years. Among 351 participants with adrenal tumors, 337 were diagnosed with an adrenocortical adenoma, 14 with another benign nodule, and none with a malignant mass. In 212 participants with an adenoma who completed endocrine testing, 69.3% were diagnosed with a nonfunctioning adenoma, 18.9% with cortisol autonomy, 11.8% with primary aldosteronism, and none with pheochromocytoma. Proportions of nonfunctioning adenomas were similarly high in various age groups (72.2%, 67.8%, and 72.2% in those aged <46, 46 to 65, and ≥66 years, respectively). LIMITATION: Only 212 of 337 participants with an adrenocortical adenoma had endocrine testing. CONCLUSION: The prevalence of adrenal tumors in the general adult screening population is 1.4%, and most of these tumors are nonfunctioning regardless of patient age. Cortisol and aldosterone secretion are the main causes of functional adenomas. PRIMARY FUNDING SOURCE: National Key Research and Development Program of China and National Natural Science Foundation of China.

Preclinical biocompatibility and biosafety evaluation of a new foldable brown diaphragm intraocular lens: An in vitro and in vivo study.

BACKGROUND: A new foldable brown diaphragm intraocular lens (IOL) was preclinically evaluated in vitro and in vivo by comparing its biocompatibility and biosafety with those of a commercially available IOL. METHODS: The new foldable iris-diaphragm IOL is composed of hydrophobic acrylic material, with a transparent optical zone and surrounding brown diaphragm. Cellular experiments evaluating lens epithelial cell morphology, adhesion, and migration were conducted to exclude cytotoxic effects. Twelve New Zealand rabbits underwent implantation of a brown diaphragm IOL in one eye, whilst an additional 12 had a commercially available foldable IOL implanted, followed by slit-lamp evaluations of inflammatory reactions and capsular opacification. Corneal endothelial cells density was measured before and after implantation. Aqueous humour samples were obtained weekly for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to investigate dye leakage from the brown-diaphragm IOL. Following 12 weeks of observation, haematoxylin and eosin staining of ocular tissue and scanning electron microscopy (SEM) of the IOL surface were performed. RESULTS: Results from in vivo experiments found no statistically significant differences between the two groups in terms of postoperative inflammation and capsular biocompatibility. No significant changes in corneal endothelial cell density were observed in either group before and after surgery. LC-MS/MS analysis showed that the target dye was not detected in aqueous humour samples. Histopathology of ocular sections and SEM imaging of IOL surfaces showed similar changes in both groups. CONCLUSIONS: The newly invented IOL showed good biocompatibility and biosafety. Combined with its foldability and peripheral shading, it could be a new choice for patients with iris defects.

Two New 4-Hydroxy-2-pyridone Alkaloids with Antimicrobial and Cytotoxic Activities from Arthrinium sp. GZWMJZ-606 Endophytic with Houttuynia cordata Thunb.

Two new 4-hydroxy-2-pyridone alkaloids furanpydone A and B (1 and 2), along with two known compounds N-hydroxyapiosporamide (3) and apiosporamide (4) were isolated from the endophytic fungus Arthrinium sp. GZWMJZ-606 in Houttuynia cordata Thunb. Furanpydone A and B had unusual 5-(7-oxabicyclo[2.2.1]heptane)-4-hydroxy-2-pyridone skeleton. Their structures including absolute configurations were determined on the basis of spectroscopic analysis, as well as the X-ray diffraction experiment. Compound 1 showed inhibitory activity against ten cancer cell lines (MKN-45, HCT116, K562, A549, DU145, SF126, A-375, 786O, 5637, and PATU8988T) with IC50 values from 4.35 to 9.72 µM. Compounds 1, 3 and 4 showed moderate inhibitory effects against four Gram-positive strains (Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus Subtilis, Clostridium perfringens) and one Gram-negative strain (Ralstonia solanacarum) with MIC values from 1.56 to 25 µM. However, compounds 1-4 showed no obvious inhibitory activity against two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and two pathogenic fungi (Candida albicans and Candida glabrata) at 50 µM. These results show that compounds 1-4 are expected to be developed as lead compounds for antibacterial or anti-tumor drugs.

Indole Diterpene Derivatives from the Aspergillus flavus GZWMJZ-288, an Endophytic Fungus from Garcinia multiflora.

A new indole diterpene, 26-dihydroxyaflavininyl acetate (1), along with five known analogs (2-6) were isolated from the liquid fermentation of Aspergillus flavus GZWMJZ-288, an endophyte from Garcinia multiflora. The structures of these compounds were identified through NMR, MS, chemical reaction, and X-ray diffraction experiments. Enzyme inhibition activity screening found that compounds 1, 4, and 6 have a good binding affinity with NPC1L1, among which compound 6 exhibited a stronger binding ability than ezetimibe at a concentration of 10 µM. Moreover, compound 5 showed inhibitory activity against α-glucosidase with an IC50 value of 29.22 ± 0.83 µM, which is 13 times stronger than that of acarbose. The results suggest that these aflavinine analogs may serve as lead compounds for the development of drugs targeting NPC1L1 and α-glucosidase. The binding modes of the bioactive compounds with NPC1L1 and α-glucosidase were also performed through in silico docking studies.

A case of gynandromorphism in Hyalomma anatolicum (Ixodida: Ixodidae).

We present a field-collected Hyalomma anatolicum gynandromorph in Xinjiang, China. Compared to the normal H. anatolicum, the gynandromorphic tick was a typical bipartite protogynander: half of the tick body displayed normal female traits, whereas the other side showed normal male traits. The engorged gynandromorphic tick laid hundreds of eggs, and the eggs looked normal.

Dilated Optic Nerve Sheath Diameter Predicts Poor Outcome in Acute Spontaneous Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Optic nerve sheath diameter (ONSD) enlargement occurs in patients with intracerebral hemorrhage (ICH). However, the relationship between ONSD and prognosis of ICH is uncertain. This study aimed to investigate the predictive value of ONSD on poor outcome of patients with acute spontaneous ICH. METHODS: We studied 529 consecutive patients with acute spontaneous ICH who underwent initial CT within 6 h of symptom onset between October 2016 and February 2019. The ONSDs were measured 3 mm behind the eyeball on initial CT images. Poor outcome was defined as having a Glasgow Outcome Scale (GOS) score of 1-3, and favorable outcome was defined as having a GOS score of 4-5 at discharge. RESULTS: The ONSD of the poor outcome group was significantly greater than that of the favorable outcome group (5.87 ± 0.86 vs. 5.21 ± 0.69 mm, p < 0.001). ONSD was related to hematoma volume (r = 0.475, p < 0.001). Adjusting other meaningful predictors, ONSD (OR: 2.83; 95% CI: 1.94-4.15) was associated with poor functional outcome by multivariable logistic regression analysis. Receiver operating characteristic curve showed that the ONSD improved the accuracy of ultraearly hematoma growth in the prediction of poor outcome (AUC: 0.790 vs. 0.755, p = 0.016). The multivariable logistic regression model with all the meaningful predictors showed a better predictive performance than the model without ONSD (AUC: 0.862 vs. 0.831, p = 0.001). CONCLUSIONS: The dilated ONSD measured on initial CT indicated elevated intracranial pressure and poor outcome, so appropriate intervention should be taken in time.

Sulfur-Containing Phenolic Compounds from the Cave Soil-Derived Aspergillus fumigatus GZWMJZ-152.

Six new sulfur-containing phenolic compounds (1-6) and their putative metabolic precursors (7-9) were isolated from the cave soil-derived fungus Aspergillus fumigatus GZWMJZ-152. Compound 1 represents an unusual benzophenone-diketopiperazine hybrid via a thioether linker, while compound 2 contains a naturally rare sulfoxide group. Both compounds 2 and 3 were initially isolated as racemic mixtures and then purified as the enantiomerically pure (+)-2, (-)-2, (+)-3, and (-)-3, respectively. Their structures, including absolute configurations, were elucidated by spectroscopic analysis, X-ray diffraction, and the calculations of electronic circular dichroism. The antioxidant activity of compounds 1-9 was evaluated based on oxygen radical absorbance capacity, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, and the protective effect on the PC12 cell line against H2O2-induced damage. Compounds 5-7 and 9 showed radical-scavenging activity against 2,2-diphenyl-1-picrylhydrazyl free radicals with the IC50 values of 3.45 ± 0.02, 23.73 ± 0.08, 18.90 ± 0.16, and 17.27 ± 0.15 µM, respectively. Compounds (±)-2, 4, 7, and 8 exhibited potent antioxidant capacity with oxygen radical absorbance capacity values of 1.73 ± 0.13, 1.65 ± 0.03, 6.14 ± 0.35, and 1.55 ± 0.04 µmol TE/µmol, respectively. Compounds (±)-2 and (±)-3 also exhibited protective effects on oxidative injury of PC12 cells induced by H2O2.

Comparison of four neonatal transport scoring methods in the prediction of mortality risk in full-term, out-born infants: a single-center retrospective cohort study.

Neonatal transport scoring systems can assess severity before and after transport, improve transport efficiency, and predict the occurrence of critical illness. The aim of this study was to compare four neonatal transport scoring methods to predict mortality risk and clinical utility within the first week after transportation. This was a single-center retrospective cohort study. All patients were full-term, out-born neonates. Each patient was assessed by the Transport Risk Index of Physiologic Stability (TRIPS), Mortality Index for Neonatal Transportation (MINT), Transport-Related Mortality Score (TREMS), and Neonatal Critical Illness Score (NCIS) scoring methods. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) for each method were compared for their utility in predicting mortality risk within the 1st week after admission. In total, 368 full-term infants were included (368/770, 47.8% of all transported infants). Within the 1st week after admission, five infants (1.36%, 5/368) died while receiving advanced life support and full treatment, and 24 infants (6.52%, 24/368) died soon after they were discharged against medical advice. The areas under the curve (AUCs) for the MINT, TRIPS, TREMS, and NCIS for the prediction of mortality were 0.822, 0.827, 0.643, and 0.731, respectively (all p < 0.05). However, the clinical net benefits for the MINT and TRIPS were far superior than those for the NCIS and TREMS. CONCLUSION: It was concluded that the TRIPS and MINT might be more suitable for the prediction of mortality in full-term, out-born neonates in the neonatal intensive care unit (NICU) within the 1st week after transportation. WHAT IS KNOWN: • Neonatal transport scores can assess not only the mortality risk during transportation but also the mortality risk of critically ill newborns after admission to the NICU. • The effectiveness of neonatal transport scores in predicting mortality risk is different. WHAT IS NEW: • Our data indicate that the diagnostic efficacy of the MINT, TRIPS, and NCIS in the prediction of full-term infant mortality was high. • The TRIPS and MINT scores had better clinical utility and could be used to predict mortality within the 1st week after transportation in full-term out-born neonates.

China's ecosystem service value in 1992-2018: Pattern and anthropogenic driving factors detection using Bayesian spatiotemporal hierarchy model.

Maintaining ecosystem services (ESs) and reducing ecosystem degradation are important goals for achieving sustainable development. However, under the influence of various anthropogenic factors, the total ecosystem service value (ESV) of China continues to decline, and the detailed processes involved in this decline are unclear. In this paper, a new long-term annual land cover dataset (the Climate Change Initiative Land Cover or CCI-LC dataset) with a spatial resolution of 300 m was employed to estimate the ESV of China, and Bayesian spatiotemporal hierarchy models were built to examine the detailed patterns and anthropogenic driving factors. From 1992 to 2018, the total ESV of China fluctuated and decreased from 3265.3 to 3253.29 billion US$ at an average rate of 0.55 billion US$ per year. Furthermore, the model revealed the spatiotemporal variations in the ESV pattern, and simultaneously detected the influences of 9 variables related to economic factors, population, infrastructure, energy, agriculture and ecological restoration, providing a convenient and effective method for ESV spatiotemporal analysis. The results enrich our understanding of the detailed spatiotemporal variation and anthropogenic driving factors underlying the declining ESV in China. These findings have substantial guiding implications for adjusting ecological regulation policies.

Prediction and validation of cross-protective candidate antigen of Hyalomma asiaticum cathepsin L between H. asiaticum and H. anatolicum.

Hyalomma asiaticum and H. anatolicum are tick species in Eurasia and Africa with major medical and veterinary significance. Beside their direct pathogenic effects, H. asiaticum and H. anatolicum are vectors of important diseases of livestock and in some instances of zoonoses. In search of ways to address the increasing incidence of global acaricide resistance, tick control through vaccination is regarded as a sustainable alternative approach. Cathepsin L-like cysteine protease (CPL) is a potent hemoglobinase, and plays important roles in the digestion of blood acquired from a host. CPL from H. anatolicum (HanCPL) with high similarity (> 90%) for H. asiaticum CPL (HasCPL) were aligned by in silico analysis. After further in vitro validation, the anti-HasCPL sera have cross-reactivity between the different total native protein of life stages and tissues for H. asiaticum and H. anatolicum. Furthermore, we further confirmed that recombinant HasCPL (rHasCPL) immunized rabbits were partially cross-protected (54.8%) by H. anatolicum infestation.

LiCl attenuates impaired learning and memory of APP/PS1 mice, which in mechanism involves α7 nAChRs and Wnt/ß-catenin pathway.

We examined the mechanism by which lithium chloride (LiCl) attenuates the impaired learning capability and memory function of dual-transgenic APP/PS1 mice. Six- or 12-month-old APP/PS1 and wild-type (WT) mice were randomized into four groups, namely WT, WT+Li (100 mg LiCl/kg body weight, gavage once daily), APP/PS1 and APP/PS1+Li. Primary rat hippocampal neurons were exposed to ß-amyloid peptide oligomers (AßOs), LiCl and/or XAV939 (inhibitor of Wnt/ß-catenin) or transfected with small interfering RNA against the ß-catenin gene. In the cerebral zone of APP/PS1 mice, the level of Aß was increased and those of α7 nicotinic acetylcholine receptors (nAChR), phosphor-GSK3ß (ser9), ß-catenin and cyclin D1 (protein and/or mRNA levels) reduced. Two-month treatment with LiCl at ages of 4 or 10 months weakened all of these effects. Similar expression variations were observed for these proteins in primary neurons exposed to AßOs, and these effects were attenuated by LiCl and aggravated by XAV939. Inhibition of ß-catenin expression lowered the level of α7 nAChR protein in these cells. LiCl attenuates the impaired learning capability and memory function of APP/PS1 mice via a mechanism that might involve elevation of the level of α7 nAChR as a result of altered Wnt/ß-catenin signalling.

Efficient Electron Transfer from Electron-Sponge Polyoxometalate to Single-Metal Site Metal-Organic Frameworks for Highly Selective Electroreduction of Carbon Dioxide.

In this work, by combining the superiority of polyoxometalates (POMs) and catalytic single-metal site Co of metalloporphyrin, a series of mixed-valence POM-based metal-organic frameworks (MOFs) composites is synthesized by a post-modification method. The electron-transfer property of POM@PCN-222(Co) composite is significantly enhanced owing to the directional electron-transfer from POM to single-metal site Co in PCN-222(Co). In particular, H-POM@PCN-222(Co) gives a high Faradaic efficiency of 96.2% for electroreduction of CO2 into CO and good stability over 10 h. DFT calculations confirm that the directional electron transfer, which accelerates the multi-electron transfer from the electrode to active single-metal site Co, enriches the electron density of the Co center, and ultimately reduces the energy of the rate-determining step, thus increasing the catalytic activity of CO2 reduction reaction (CO2 RR). This work therefore suggests some new insight for the design of efficient electrocatalysts for CO2 RR.