Special clinical features with a novel mutation site of CHN1 gene in a Chinese family with Duane retraction syndrome.

PURPOSE: This study is to describe the special clinical and genotypic features of a Chinese family with variant types of Duane retraction syndrome and to present our experience on managing these cases. METHODS: Four individuals from one family were reviewed by ophthalmologic examinations, in which two affected and two unaffected individuals were revealed. MRI scans were performed on the two patients. Relevant gene mutations were screened by the next-generation sequencing technology and confirmed by Sanger sequencing technology. RESULTS: The six-year-old proband presented with special clinical features of severe horizontal gaze dysfunction, exotropia and mild scoliosis. His mother showed significantly limited binocular abductions, with retraction of eyeballs in adduction. From MRI scans, abducens nerves were not observed in both patients and the oculomotor nerve was slightly thin in the proband. The proband and his mother shared the same CHN1 gene mutation site (c. 62A>G; p.Y21C). Strabismus surgery was performed on the proband to correct the primary gaze exotropia.(NM_001822: exon3 or NM_001025201: exon4: c. 62A>G; p.Y21C). CONCLUSIONS: A novel CHN1 gene mutation was revealed from a Chinese family with Duane retraction syndrome. Remarkably, the proband and his mother presented different clinical features of ocular motility disorder. Strabismus correction surgery and amblyopia training helped to improve the appearance and visual function of the proband.

Acacetin inhibits inflammation by blocking MAPK/NF-κB pathways and NLRP3 inflammasome activation.

Objective: Our preliminary research indicates that acacetin modulates the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome, providing protection against Alzheimer's Disease (AD) and cerebral ischemic reperfusion injury. The mechanisms of acacetin to inhibit the activation of the NLRP3 inflammasome remain fully elucidated. This study aims to investigate the effects and potential mechanisms of acacetin on various agonists induced NLRP3 inflammasome activation. Methods: A model for the NLRP3 inflammasome activation was established in mouse bone marrow-derived macrophages (BMDMs) using Monosodium Urate (MSU), Nigericin, Adenosine Triphosphate (ATP), and Pam3CSK4, separately. Western blot analysis (WB) was employed to detect Pro-caspase-1, Pro-Interleukin-1ß (Pro-IL-1ß) in cell lysates, and caspase-1, IL-1ß in supernatants. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measured the release of IL-1ß, IL-18, and Tumor Necrosis Factor-alpha (TNF-α) in cell supernatants to assess the impact of acacetin on NLRP3 inflammasome activation. The lactate dehydrogenase (LDH) release was also assessed. The Nuclear Factor Kappa B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways related proteins were evaluated by WB, and NF-κB nuclear translocation was observed via laser scanning confocal microscopy (LSCM). Disuccinimidyl Suberate (DSS) cross-linking was employed to detect oligomerization of Apoptosis-associated Speck-like protein containing a Caspase Recruitment Domain (ASC), and LSCM was also used to observe Reactive Oxygen Species (ROS) production. Inductively Coupled Plasma (ICP) and N-(6-methoxyquinolyl) acetoethyl ester (MQAE) assays were utilized to determined the effects of acacetin on the efflux of potassium (K+) and chloride (Cl-) ions. Results: Acacetin inhibited NLRP3 inflammasome activation induced by various agonists, reducing the release of TNF-α, IL-1ß, IL-18, and LDH. It suppressed the expression of Lipopolysaccharides (LPS)-activated Phosphorylated ERK (p-ERK), p-JNK, and p-p38, inhibited NF-κB p65 phosphorylation and nuclear translocation. Acacetin also reduced ROS production and inhibited ASC aggregation, thus suppressing NLRP3 inflammasome activation. Notably, acacetin did not affect K+ and Cl-ions efflux during the activation process. Conclusion: Acacetin shows inhibitory effects on both the priming and assembly processes of the NLRP3 inflammasome, positioning it as a promising new candidate for the treatment of NLRP3 inflammasome-related diseases.

Prevalence and Risk Factors of Hyperuricemia in the Urban Health Checkup Population in Xinjiang, China: A Cross-Sectional Study.

Purpose: In this study, the aim was to investigate the prevalence and risk factors of hyperuricemia (HUA) in the urban health checkup population in Urumqi, Xinjiang, and thus provide clues for the prevention of HUA. Methods: People who attended medical examinations from May 2021 to June 2022 at a hospital in Urumqi, Xinjiang, were selected for evaluation based on their general information, physical examination results, and laboratory test results. The chi-square test was used to determine whether there was a difference in the prevalence of HUA among participants with different characteristics. Using logistic regression analyses, risk factors for HUA were identified. Results: There were 8722 participants diagnosed with HUA, with an overall prevalence of 26.96%. The prevalence in men was 37.72%, significantly higher than in women (13.29%). Participants were characterized by a multiethnic composition, with Han (28.61%), Hui (27.88%) and Manchu (38.46%) being the three ethnicities with the highest prevalence. According to logistic regression analyses, HUA was associated with age, ethnicity, residence, marital status, body mass index (BMI), diastolic blood pressure (DBP), fasting blood glucose (FPG), triglyceride glucose (TyG) index, abdominal obesity, and dyslipidemia differently in males and females. Conclusion: The prevalence of HUA was high in the urban health checkup population in Urumqi, Xinjiang, particularly among men and youth. The early intervention for HUA should be enhanced to reduce the risk of cardiovascular disease and other related conditions.

Acacetin improves cognitive function of APP/PS1 Alzheimer's disease model mice via the NLRP3 inflammasome signaling pathway.

Background: Acacetin (5,7-dihydroxy-4'-methoxyflavone), one of the main extractions from Saussurea involucrata, has anti-inflammatory effects. Our previous study found that acacetin inhibited the Nod-like receptor pyrin domain containing 3 (NLRP3) signaling pathway after cerebral ischemia-reperfusion injury. NLRP3 inflammasome plays a role in Alzheimer's disease (AD) process. However, few studies have examined the effects of acacetin in AD. Methods: We randomly divided APP swe/PS1dE9 double transgenic mice into acacetin group (intraperitoneal injection of 25 mg/kg acacetin) and AD model group (intraperitoneal injection of same volume of saline). C57BL/6 mice were selected as control group (same treatment with AD model group). After treating for 30 days, a Morris water maze test was conducted to evaluate spatial learning and memory of the mice. Senile plaque (SP) formation was evaluated by immunohistochemistry. NLRP3 inflammasome-related inflammatory factors and amyloid-ß-42 were detected by Western blot or enzyme-linked immunosorbent assay. Results: Acacetin improved spatial learning and memory of AD mice and reduced APP/ß expression, thereby decreasing SP formation in the brain. Acacetin also reduced the expression of NLRP3, cysteinyl aspartate-specific proteinase 1 (caspase-1), and interleukin-1ß (IL-1ß) and the release of inflammatory factors, tumor necrosis factor-α (TNF-α) and IL-1ß. Conclusions: Acacetin improved the learning and memory abilities of AD mice and exerted a protective effect on AD by inhibiting the NLRP3 signaling pathway and reducing SP formation.

Regulation of Notch1 and Foxp1 by MiR-34a in psoriasis vulgaris / Regulación de Notch1 y Foxp1 por MiR-34ª en psoriasis vulgaris

SUMMARY: This study is to investigate the regulation of Notch1 and Foxp1 by miR-34a in the development of psoriasis vulgaris. RT-PCR was used to compare the levels of miR-34a in the skin lesions of 20 patients with psoriasis vulgaris and 20 normal skin tissues. Immunohistochemistry was used to detect the expression of Notch1 and Foxp1 in 51 patients with psoriasis vulgaris, which were further compared with that in 29 normal control tissues. In addition, in HaCaT cells, we used miR-34a mimics and inhibitors to overexpress and inhibit miR-34a, respectively, and detected the mRNA and protein levels of miR-34a, Notch1, and Foxp1. The level of miR-34a in the skin lesions of patients with psoriasis vulgaris was significantly higher than that in normal skin tissues (t=2.192, P<0.05). The positive rate of Notch1 in the skin lesions of patients with psoriasis vulgaris was 76.47 %, which was significantly higher than that in normal skin tissues (13.79 %) (t=29.215, P<0.01). The positive rate of FOXP1 in the psoriasis vulgaris group was 92.16 %, which was also significantly higher than that in the normal skin group (65.52 %) (t=9.087, P<0.01). In addition, overexpression of miR-34a significantly promoted the expression of Notch1 and Foxp1. However, inhibition of miR-34a significantly reduced Notch1 and Foxp1 levels. miR- 34a is highly expressed in the skin tissues of patients with psoriasis vulgaris, and may participate in the development of psoriasis vulgaris by regulating Notch1 and Foxp1.

RESUMEN: El objetivo de este estudio fue investigar la regulación de Notch1 y Foxp1 por miR-34a en el desarrollo de la psoriasis vulgar. Se utilizó RT-PCR con el fin de comparar los niveles de miR-34a en las lesiones cutáneas de 20 pacientes con psoriasis vulgar y 20 tejidos de piel normales. Se utilizó inmunohistoquímica para detectar la expresión de Notch1 y Foxp1 en 51 pacientes con psoriasis vulgar, que se compararon además con la de 29 tejidos normales control. Además, en las células HaCaT, usamos miméticos e inhibidores de miR-34a para sobreexpresar e inhibir miR-34a, respectivamente, y detectamos los niveles de ARNm y proteína de miR-34a, Notch1 y Foxp1. El nivel de miR- 34a en las lesiones cutáneas de pacientes con psoriasis vulgar fue significativamente mayor que en los tejidos normales de la piel (t=2,192, P<0,05). La tasa de positividad de Notch1 en las lesiones cutáneas de pacientes con psoriasis vulgar fue del 76,47 %, que fue significativamente mayor que la de los tejidos normales de la piel (13,79 %) (t=29,215, P<0,01). La tasa positiva de FOXP1 en el grupo de psoriasis vulgar fue del 92,16 %, que también fue significativamente mayor que la del grupo de piel normal (65,52 %) (t=9,087, P<0,01). Además, la sobreexpresión de miR-34a promovió significativamente la expresión de Notch1 y Foxp1. Sin embargo, la inhibición de miR-34a redujo de manera importante los niveles de Notch1 y Foxp1. miR-34a se expresa en gran medida en los tejidos de la piel en pacientes con psoriasis vulgar y puede participar en el desarrollo de la psoriasis vulgar mediante la regulación de Notch1 y Foxp1.

Learning from inbound foreign acquisitions for outbound expansion by emerging market MNEs.

Although cross-border acquisitions (CBAs) are prevalent, many such acquisitions fail to complete. This challenge is even more profound for emerging market MNEs (EMNEs). Drawing upon the vicarious learning theory, we argue that EMNEs can learn from inbound foreign acquirers through the latter's demonstration, professional services firms, and employees. This learning mechanism enables EMNEs to better deal with the complexity and uncertainty in various stages of acquiring foreign firms, thus increasing the completion rate of their outbound CBAs. We also suggest that the effectiveness of vicarious learning is further enhanced by the relatedness between inbound and outbound CBAs. Our analysis of 3599 outbound CBAs from 27 emerging economies during 2000-2018 shows that prior inbound CBAs completed in an emerging economy have a positive effect on the completion likelihood of outbound CBAs conducted by EMNEs from this economy. This positive effect becomes even stronger when the percentage of (1) inbound CBAs served by the EMNE's financial advisors, (2) inbound foreign acquirers that are in the same industry as the EMNE, and (3) inbound foreign acquirers that are from the same country as a focal outbound CBA's target country, is larger. These findings offer new insights into the inbound-outbound acquisition links and the internationalization process of EMNEs. Supplementary Information: The online version contains supplementary material available at 10.1057/s41267-022-00583-x.

Bien que les acquisitions transfrontalières (Cross-Border Acquisitions ­ CBAs) soient répandues, nombre d'entre elles ne sont pas menées à bien. Ce défi est encore plus grand pour les multinationales des marchés émergents (Emerging Market MNEs ­ EMNEs). Nous appuyant sur la théorie de l'apprentissage vicariant, nous argumentons que les EMNEs peuvent apprendre des acquéreurs étrangers entrants par le biais des démonstrations de ces derniers, des entreprises de services professionnels et des employés. Ce mécanisme d'apprentissage permet aux EMNEs de mieux gérer la complexité et l'incertitude des différentes étapes de l'acquisition d'entreprises étrangères, augmentant ainsi le taux d'achèvement de leurs CBAs sortantes. Nous suggérons également que l'efficacité de l'apprentissage vicariant est renforcée par la relation entre les CBAs entrantes et sortantes. Notre analyse de 3599 CBAs sortantes de 27 économies émergentes entre 2000 et 2018 montre que les CBAs entrantes antérieures réalisées dans une économie émergente ont un impact positif sur la probabilité d'achèvement des CBAs sortantes réalisées par les EMNEs de cette économie. Cet impact positif devient encore plus fort lorsque le pourcentage (1) de CBAs entrantes servies par les conseillers financiers de l'EMNE, (2) d'acquéreurs étrangers entrants appartenant au même secteur d'activité que l'EMNE, et (3) d'acquéreurs étrangers entrants provenant du même pays que le pays cible d'une CBA sortante focale, est plus élevé. Ces résultats apportent de nouveaux renseignements sur les liens entre les acquisitions entrantes et sortantes, ainsi que sur le processus d'internationalisation des EMNEs.

Aunque las adquisiciones transfronterizas (CBAs por sus iniciales en inglés) son frecuentes, muchas de ellas no consiguen completarse. Este reto es aún más profundo para las empresas multinacionales de mercados emergentes (EMNE por sus iniciales en inglés). Basándonos en la teoría del aprendizaje vicario, argumentamos que las empresas multinacionales de mercados emergentes pueden aprender de los adquirentes extranjeros entrantes a través de la demostración de estos últimos, de las empresas de servicios profesionales y de los empleados. Este mecanismo de aprendizaje permite a las empresas multinacionales de mercados emergentes afrontar mejor la complejidad y la incertidumbre en varias etapas de la adquisición de empresas extranjeras, aumentando así la tasa de finalización de sus adquisiciones transfronterizas salientes. También sugerimos que la eficacia del aprendizaje vicario se ve reforzada por la relación entre las adquisiciones transfronterizas entrantes y salientes. Nuestro análisis de 3.599 adquisiciones transfronterizas salientes de 27 economías emergentes durante 2000­2018 muestra que las adquisiciones transfronterizas entrantes anteriores completados en una economía emergente tienen un efecto positivo en la probabilidad de finalización de las adquisiciones transfronterizas salientes realizados por las empresas multinacionales de mercados emergentes de esta economía. Este efecto positivo se hace aún más fuerte cuando el porcentaje de (1) las adquisiciones transfronterizas entrantes atendidos por los asesores financieros de la empresa multinacional de mercados emergentes, (2) adquirentes extranjeros entrantes que están en la misma industria que la empresa multinacional de mercados emergentes, y (3) adquirentes extranjeros entrantes que son del mismo país que el país objetivo de una adquisición transfronteriza saliente focal, es mayor. Estos resultados ofrecen nuevas perspectivas sobre los vínculos de adquisición entrante-saliente y el proceso de internacionalización de las empresas multinacionales de mercados emergentes.

Embora as aquisições transfronteiriças (CBAs) sejam predominantes, muitas dessas aquisições não têm sucesso na sua conclusão. Esse desafio é ainda mais profundo para MNEs de mercados emergentes (EMNEs). Com base na teoria da aprendizagem vicária, argumentamos que EMNEs podem aprender com compradores estrangeiros entrantes por meio de sua demonstração, empresas de serviços profissionais e funcionários. Esse mecanismo de aprendizagem permite que EMNEs lidem melhor com a complexidade e a incerteza em vários estágios de aquisição de empresas estrangeiras, dessa forma aumentando a taxa de conclusão de suas CBAs. Também sugerimos que a eficácia da aprendizagem vicária é ainda mais reforçada pela relação entre CBAs de entrada e saída. Nossa análise de 3.599 CBAs de saída de 27 economias emergentes durante 2000­2018 mostra que CBAs de entrada anteriores concluídas em uma economia emergente têm um efeito positivo na probabilidade de conclusão de CBAs de saída conduzidas por EMNEs dessa economia. Este efeito positivo torna-se ainda mais pronunciado quando é maior o percentual de (1) CBAs de entrada atendidos por consultores financeiros da EMNE, (2) adquirentes estrangeiros de entrada que são da mesma indústria que a EMNE e (3) adquirentes estrangeiros de entrada que são do mesmo país do destino de uma CBA de saída. Essas descobertas oferecem novos insights sobre as conexões de aquisição de entrada e saída e o processo de internacionalização de EMNEs.

Geosynchronous Satellite GF-4 Observations of Chlorophyll-a Distribution Details in the Bohai Sea, China.

We analyzed the distribution of chlorophyll-a (Chla) in the Bohai Sea area based on data from the geosynchronous orbit optical satellite Gaofen-4 (GF-4), which was launched in 2015, carrying a panchromatic multispectral sensor (PMS). This is the first time the geosynchronous orbit optical satellite GF-4 remote-sensing data has been used in China to detect the Chla change details in the Bohai Sea. A new GF-4 retrieved model was established based on the relationship between in situ Chla value and the reflectance combination of 2 and 4 bands, with the R2 of 0.9685 and the total average relative error of 37.42%. Twenty PMS images obtained from 2017 to 2019 were applied to analyze Chla in Bohai sea. The results show that: (1) the new built Chla inversion model PMS-1 for the GF-4 PMS sensor can extract Chla distribution details in the Bohai Sea well. The high Chla content in the Bohai Sea is mainly located in coastal areas, such as the top of Laizhou Bay, Bohai Bay and Liaodong Bay, with the value being around 13 µg/L. The concentration of Chla in the Bohai Strait and northern Yellow Sea is relatively low with the value being around 5 µg/L. (2). Taking full advantage of the continuous observation of geostationary orbit satellite, GF-4 with a high-resolution sensor PMS of 50 m can effectively detect short-term change (changes within 10 min) in Chla concentration. The changes mainly appear at the southwest and northeast costal area as well as in the center of Bohai Sea with the change value of around 3 µg/L. (3) The change of Chla concentration in the Bohai sea is related to the environmental factors such as seawater temperature, salinity, illumination and nutrient salts, as well as the dynamic factors such as wind, flow field and tidal current.

The efficacy of modified posterior scleral reinforcement with round scleral patches in Chinese children with high myopia.

PURPOSE: To observe the efficacy of modified Snyder-Thompson posterior scleral reinforcement with round scleral patches in Chinese children with high myopia. METHODS: This retrospective study included 46 Chinese children with high myopia (72 eyes) who underwent modified Snyder-Thompson posterior scleral reinforcement (PSR) with round scleral patches and 43 Chinese children with high myopia (67 eyes) who wore only spectacles as a control group. Both groups attended a follow-up at 3 years. Axial length (AL), spherical equivalent (SE), best-corrected visual acuity (BCVA), and full ocular assessment results were evaluated at the initial and final visits. Complications were recorded. RESULTS: AL had increased by 0.29 ± 0.33 mm in the PSR group and 0.82 ± 0.33 mm in the control group (P < 0.0001) at the final follow-up. The change in the SE was 0.31 ± 0.81 D in the PSR group and 2.25 ± 1.02 D in the control group (P < 0.0001). A decrease of 0.02 ± 0.11 LogMAR was found in the control group, and a change of 0.22 ± 0.35 LogMAR was found in the PSR group. No serious complications due to PSR surgery occurred. CONCLUSIONS: Modified Snyder-Thompson PSR surgery with round scleral patches can effectively limit the progression of axial elongation in Chinese children with high myopia. The operation is safe, causes little damage, and can be customized.

Engineering of monodisperse core-shell up-conversion dendritic mesoporous silica nanocomposites with a tunable pore size.

Fabricating lanthanide doped up-conversion luminescence based nanocomposites has drawn increasing attention in nanoscience and nanotechnology. Although challenging in precise synthesis, structure manipulation and interfacial engineering, fabricating dendritic mesoporous silica coated up-conversion nanoparticles (UCNP@dMSNs) with a tunable pore size is of great importance for the functionalization and application of UCNPs. Herein, we report a strategy to prepare uniform monodisperse UCNP@dMSNs with a core-shell structure. The silica shell has tunable center-radial and dendritic mesoporous channels. The synthesis was carried out in the heterogeneous oil-water microemulsion phase of the Winsor III system reaction system, which allows silica to be deposited directly on hydrophobic UCNPs through the self-anchoring of micelle complexes on the oleic acid ligand. The average pore size of UCNP@dMSNs could be tailored from ∼10 to ∼35 nm according to the varied amounts of co-solvent in the mixture. The microemulsion approach could also be used to prepare hierarchical UCNP@dMSNs with a multi-generational mesostructure. The resultant UCNP@dMSNs exhibit the unique advantage of loading "guest" nanoparticles in a self-absorption manner. We proved that Cu1.8S NPs (∼10 nm), Au NPs (∼10 nm) and Fe3O4 NPs (∼25 nm) could be incorporated in UCNP@dMSNs, which in turn validates the high adsorption capacity of UCNP@dMSNs.

Acacetin protects against cerebral ischemia-reperfusion injury via the NLRP3 signaling pathway.

Acacetin (5,7-dihydroxy-4'-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3 (NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin (acacetin group) or an equal volume of saline (0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1 (Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1ß and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1ß, and interleukin-1ß were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway.

Sensitive and simultaneous determination of nine anticoagulant rodenticides in human blood by UPLC-MS-MS with phospholipid removal pretreatment.

A sensitive and rapid method for the simultaneous determination of nine anticoagulant rodenticides (ARs) in human blood is reported herein. The method involves phospholipid removal pretreatment for reduced matrix effect (ME) and detection with ultra-performance liquid chromatography coupled with tandem mass spectrometry. Satisfactory recoveries were achieved ranging from 80.6% to 113.1% for the nine analytes, with the intra-day relative standard deviations (RSDs) in the range of 3.4-7.9% and inter-day RSDs in the range of 4.1-8.3%, indicating good precision. Linear relationships with correlation coefficients above 0.998 (n = 6) were found in the range of 1-2,000 ng/mL. High sensitivity was achieved with limits of detection ranging from 0.02 to 0.3. The application of phospholipid removal step significantly optimized the ME, and the reduction of ME ranged from 6.1% to 15.5%. This method was successfully applied to the determination of ARs for blood samples from real forensic cases. These results prove that this method is reliable for rapid forensic and clinical diagnosis. The removal capabilities for five representative phospholipids that are abundant in blood were evaluated individually with Phree™ phospholipid removal plates. While significant capabilities for phospholipid removal were confirmed, the results showed that the removal capability for certain phospholipid could be improved.

Rapid and sensitive determination of formamidines and metabolites with HPLC-MS/MS using core-shell columns.

A number of poisoning and suicide cases involving formamidine pesticides have been reported, thus developing a rapid and low cost determination method is crucial. In this work, a rapid, sensitive and low-cost method for the simultaneous determination of formamidine pesticides (amitraz, chlordimeform, formetanate) and their main metabolites, N-(2,4-dimethylphenyl)-N-methyl-formamidine, 2,4-dimethylformamidine, 2,4-dimethylaniline, 4-chloro-2-methylaniline and 3-hydroxyacetanilide in human blood by high-performance liquid chromatography with tandem mass spectrometry is developed. The application of columns with core-shell particles significantly reduced the analysis time. Very low LODs (0.01-0.04 µg L-1) were obtained for formamidine pesticides and their metabolites. The method was successfully applied to the analysis of human blood samples from a real forensic case. The significantly reduced analysis time, high sensitivity and low cost are the primary advantages of the developed method. This methodology provides important value for sensitive and rapid determination of residue pesticides and metabolites, study of residue pesticides behavior in human body, as well as application in real forensic cases.

A Gene Scan Study of RPE65 in Chinese Patients with Leber Congenital Amaurosis.

BACKGROUND: Leber congenital amaurosis (LCA) is a visual disease which is caused by RPE65 mutations and results in retinal degeneration and severe vision loss in early infancy. According to previous researches, mutations of the RPE65 gene account for 16% of all cases of LCA. This study aimed to identify RPE65 gene mutations in Chinese patients with LCA. METHODS: We recruited 52 sporadic patients from Peking University Third Hospital in 2016 and applied Sanger sequencing to identify variants among exons responsible for the disease. The genomic DNAs from blood leukocytes of these patients were isolated, and the entire coding region of the RPE65 gene was amplified by polymerase chain reaction. We then determined the sequence of RPE65 using ABI 3100 Genetic Analyzer. RESULTS: Our study identified that only 1 out of the 52 patients with LCA carried the previously unreported homozygosis missense mutation c1174A>C (T392P) of the RPE65 gene. However, the mutation was associated with the disease phenotype and not detected in 100 normal controls. CONCLUSIONS: Though we identified a novel missense mutation in the RPE65 gene that causes LCA, our result indicates that RPE65 mutations may not play a major role in the LCA patients in China since only 1 out of the 52 patients carried mutation in the RPE65 gene.

Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis.

BACKGROUND: Emerging evidence indicates that impaired angiogenesis may contribute to hypertension-induced cardiac remodeling. The nicotinamide adenine dinucleotide-dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between SIRT3-mediated angiogenesis and cardiac remodeling. METHODS AND RESULTS: Our experiments were performed on SIRT3 knockout and age-matched wild-type mice infused with angiotensin II (1400 ng/kg per minute) or saline for 14 days. After angiotensin II infusion, SIRT3 knockout mice developed more severe microvascular rarefaction and functional hypoxia in cardiac tissues compared with wild-type mice. These events were concomitant with mitochondrial dysfunction and enhanced collagen I and collagen III expression, leading to cardiac fibrosis. Silencing SIRT3 facilitated angiotensin II-induced aberrant Pink/Parkin acetylation and impaired mitophagy, while excessive mitochondrial reactive oxygen species generation limited angiogenic capacity in primary mouse cardiac microvascular endothelial cells. Moreover, SIRT3 overexpression in cardiac microvascular endothelial cells enhanced Pink/Parkin-mediated mitophagy, attenuated mitochondrial reactive oxygen species generation, and restored vessel sprouting and tube formation. In parallel, endothelial cell-specific SIRT3 transgenic mice showed decreased fibrosis, as well as improved cardiac function and microvascular network, compared with wild-type mice with similar stimuli. CONCLUSIONS: Collectively, these findings suggest that SIRT3 could promote angiogenesis through attenuating mitochondrial dysfunction caused by defective mitophagy.

A previously unidentified deletion in G protein-coupled receptor 143 causing X-linked congenital nystagmus in a Chinese family.

BACKGROUND: Congenital nystagmus (CN) is characterized by conjugated, spontaneous, and involuntary ocular oscillations. It is an inherited disease and the most common inheritance pattern is X-linked CN. In this study, our aim is to identify the disease-causing mutation in a large sixth-generation Chinese family with X-linked CN. METHODS: It has been reported that mutations in four-point-one, ezrin, radixin, moesin domain-containing 7 gene (FRMD7) and G protein-coupled receptor 143 gene (GPR143) account for the majority patients of X-linked nystagmus. We collected 8 ml blood samples from members of a large sixth-generation pedigree with X-linked CN and 100 normal controls. FRMD7 and GPR143 were scanned by polymerase chain reaction (PCR)-based DNA sequencing assays, and multiplex PCR assays were applied to detect deletions. RESULTS: We identified a previously unreported deletion covering 7 exons in GPR143 in a Chinese family. The heterozygous deletion from exon 3 to exon 9 of GPR143 was detected in all affected males in the family, while it was not detected in other unaffected relatives or 100 normal controls. CONCLUSIONS: This is the first report of molecular characterization in GPR143 gene in the CN family. Our results expand the spectrum of GPR143 mutations causing CN and further confirm the role of GPR143 in the pathogenesis of CN.

A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family.

BACKGROUND: Congenital cataract is a rare disorder characterized by crystallin denaturation, which becomes a major cause of childhood blindness. Although more than fifty pathogenic genes for congenital cataract have been reported, the genetic causes of many cataract patients remain unknown. In this study, the aim is to identify the genetic cause of a five-generation Chinese autosomal dominant congenital cataract family. METHODS: Whole exome sequencing (WES) was performed on three affected and one unaffected member of the family, known causative genes were scanned first. Sanger sequencing was used to validate co-segregation of the candidate variant in the family. The impact on the transcript and amino acid sequences of the variant was further analyzed. RESULTS: We identified a novel splice donor site mutation c. 2825+1G >A in EPHA2 that was absent in public and in-house databases and showed co-segregation in the family. This variant resulted in an altered splice that led to protein truncation. CONCLUSIONS: The mutation we identified was responsible for congenital cataract in our studied family. Our findings broaden the spectrum of causative mutations in EPHA2 gene for congenital cataract and suggest that WES is an efficient strategy to scan variants in known causative genes for genetically heterogeneous diseases.

Facile growth of well-dispersed and ultra-small MoS2 nanodots in ordered mesoporous silica nanoparticles.

A facile one-step solvothermal method was developed for the homogeneously confined growth of ultra-small (∼1.5 nm) and monodispersed 2H phase MoS2 nanodots into mesoporous silica nanoparticles (MSNs).

Inhibition of adenosine monophosphate-activated protein kinase reduces glial cell-mediated inflammation and induces the expression of Cx43 in astroglias after cerebral ischemia.

We investigated the protective effect of adenosine monophosphate-activated protein kinase (AMPK) inhibition on cerebral ischemic injury of mice, and characterized the role of AMPK inhibition on astrocytes, microglias, and neuroinflammation. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in male Kunming mice, and Compound C was used to inhibit AMPK activity. The neurobehavioral scores, infarct volumes, phosphorylation of AMPK, activation of the glial cells, levels of connexin 43 (Cx43), and related inflammatory mediators were affected by the presence or absence of AMPK inhibitor Compound C. AMPK was activated after cerebral ischemia. AMPK inhibition reduced infarct size and improved neurological outcomes after 24h reperfusion of mice. Furthermore, our study revealed that the mechanisms of neuroprotection of AMPK inhibition may be as follows: (1) inhibiting the excessive activation of astrocyte and microglia cells, (2) stabilizing the expression of protective proteins such as Cx43 in astroglias, and (3) inhibiting the release of microglial pro-inflammatory factors. These results demonstrated that AMPK inhibition attenuated cerebral ischemic injury, at least in part, by glial cell-mediated protective effects in mice.

Fluorescence sensors for Zn(2+) based on conjugated indole Schiff base.

Two novel fluorescence probes based on conjugated Schiff base for the detection of Zn(2+) were developed. Corresponding molecular geometries, orbital energies, electron contributions and absorption properties of the fluorescence probes were calculated at B3LYP/6-31G(∗) by density functional theory. The fluorescence properties of the probes were investigated by UV-vis and fluorescence spectrometer. Results indicate that the probes exhibit excellent sensitivity and selectivity for Zn(2+) compared with metal ions examined. For example, the enhancement efficiency of the compound 2 for Zn(2+) is up to 846%. The detection limit of the sensor toward Zn(2+) could low to 1.0×10(-7)M. Moreover, mechanisms for the high selectivity and sensitivity of the probes to Zn(2+) were studied.