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An effective and stereoselective synthesis of halogenated (E)-4-methylenechromanes with a sulfonyl group was developed via the copper-catalyzed sulfonylative annulation/halogenation of 1,7-enynes, in which sodium sulfinates were used as the sulfonyl reagents and tetrabutylammonium halide provided the halogen sources. The formed alkenyl C-X bonds were valuable and can efficiently undergo the subsequent hydrolysis, alkenylation, alkynylation, arylation, alkylthiolation, and alkoxylation to furnish a series of highly functionalized 4-methylenechromanes.
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Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.
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Córnea , Neovascularização da Córnea , Nanopartículas , Soluções Oftálmicas , Neovascularização da Córnea/tratamento farmacológico , Animais , Nanopartículas/química , Soluções Oftálmicas/química , Córnea/metabolismo , Córnea/efeitos dos fármacos , Camundongos , Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/farmacologia , Tamanho da Partícula , Humanos , Masculino , Camundongos Endogâmicos C57BL , CoelhosRESUMO
Vibrio parahaemolyticus is a common foodborne pathogenic bacterium. With the overuse of antibiotics, an increasing proportion of drug-resistant strains are emerging, which puts enormous pressure on public health. In this study, a V. parahaemolyticus-specific phage, VP41s3, was isolated. The head length, width, and tail length of the phage were 77.7 nm, 72.2 nm, and 17.5 nm, respectively. It remained active in the temperature range of 30-50°C and pH range of 4-11. The lytic curve of phage VP41s3 showed that the host bacteria did not grow until 11 h under phage treatment at MOI of 1000, indicating that the phage had good bacteriostatic ability. When it was added to shellfish contaminated with V. parahaemolyticus (15°C, 48 h), the number of bacteria in the experimental group was 2.11 log10 CFU/mL lower than that in the control group at 24 h. Furthermore, genomic characterization and phylogenetic analysis indicated that phage VP41s3 was a new member of the Podoviridae family. The genome contained 50 open reading frames (ORFs), in which the ORF19 (thymidine kinase) was an enzyme involved in the pyrimidine salvage pathway, which might lead to the accelerated DNA synthesis efficiency after phage entered into host cells. This study not only contributed to the improvement of phage database and the development of beneficial phage resources but also revealed the potential application of phage VP41s3 in food hygiene and safety.
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Bacteriófagos , Genoma Viral , Frutos do Mar , Vibrio parahaemolyticus , Vibrio parahaemolyticus/virologia , Frutos do Mar/microbiologia , Bacteriófagos/fisiologia , Bacteriófagos/isolamento & purificação , Microbiologia de Alimentos , Filogenia , Podoviridae/isolamento & purificação , Podoviridae/genética , Podoviridae/fisiologia , Animais , Fases de Leitura Aberta , Contaminação de Alimentos/prevenção & controleRESUMO
The eye is a very important organ, and keratitis, corneal neovascularization, floaters, age-related macular degeneration, and other vision problems have seriously affected people's quality of life. Among the ophthalmic treatments, laser photocoagulations have been proposed and have shown therapeutic effects in clinical settings. However, corneal thinning and bleeding lesions induced by laser damage have led to limit its applications. To treat the issues of traditional hyperthermia treatments, photosensitizers [e.g., indocyanine green (ICG)] have been investigated to increase the therapeutic effects of corneal neovascularization and choroidal neovascularization. In the recent study, with the help of ICG, laser-induced nanobubble was proposed to treat vitreous opacities. The developed strategies could enlarge the effect of laser irradiation and reduce the side effects, so as to expand the scope of laser treatments in clinical ophthalmic diseases.
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The incidence of ulcerative colitis (UC) has increased globally. As a complex disease, the genetic predisposition for UC could be estimated by the polygenic risk score (PRS), which aggregates the effects of a large number of genetic variants in a single quantity and shows promise in identifying individuals at higher lifetime risk of UC. Here, based on a cohort of 2869 UC cases and 2900 controls with genotype array datasets, we used PRSice-2 to calculate PRS, and systematically analyzed factors that could affect the power of PRS, including GWAS summary statistics, population stratification, and impact of variants. After leveraging a stepwise condition analysis, we eventually established the best PRS model, achieving an AUC of 0.713. Meanwhile, samples in the top 20% of the PRS distribution had a risk of UC more than ten times higher than samples in the lowest 20% (OR = 10.435, 95% CI 8.571-12.703). Our analyses demonstrated that including population-enriched, more disease-associated SNPs and using GWAS summary statistics from similar ethnic background can improve the power of PRS. Strictly following the principle of focusing on one population in all aspects of generating PRS can be a cost-effective way to apply genotype-array-derived PRS to practical risk estimation.
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Colite Ulcerativa , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , População Branca , Humanos , Colite Ulcerativa/genética , Herança Multifatorial/genética , Estudo de Associação Genômica Ampla/métodos , População Branca/genética , Feminino , Masculino , Fatores de Risco , Estudos de Casos e Controles , GenótipoRESUMO
The clinical experience of Shao's needling technique for post-stroke depression is introduced. Professor SHAO Jingming proposes that the main pathogenesis of this condition lies in the "imbalance of body and spirit," with its onset closely related to the heart, liver, spleen, and kidney. In clinical practice, based on the principle of "treating both the body and spirit", "three acupoints for treating the spirit" including Dazhui (GV 14), Fengchi (GB 20), and Baihui (GV 20) are selected, combined with back-shu points such as Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20), and Shenshu (BL 23). The nu-needle manipulation method is applied. The treatment focuses on both physical and mental aspects, achieving remarkable therapeutic effects.
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Pontos de Acupuntura , Terapia por Acupuntura , Depressão , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Terapia por Acupuntura/métodos , Depressão/terapia , Depressão/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) and Parkinson's disease (PD) are chronic disorders that have been suggested to share common pathophysiological processes. LRRK2 has been implicated as playing a role in both diseases. Exploring the genetic basis of the IBD-PD comorbidity through studying high-impact rare genetic variants can facilitate the identification of the novel shared genetic factors underlying this comorbidity. METHODS: We analyzed whole exomes from the BioMe BioBank and UK Biobank, and whole genomes from a cohort of 67 European patients diagnosed with both IBD and PD to examine the effects of LRRK2 missense variants on IBD, PD and their co-occurrence (IBD-PD). We performed optimized sequence kernel association test (SKAT-O) and network-based heterogeneity clustering (NHC) analyses using high-impact rare variants in the IBD-PD cohort to identify novel candidate genes, which we further prioritized by biological relatedness approaches. We conducted phenome-wide association studies (PheWAS) employing BioMe BioBank and UK Biobank whole exomes to estimate the genetic relevance of the 14 prioritized genes to IBD-PD. RESULTS: The analysis of LRRK2 missense variants revealed significant associations of the G2019S and N2081D variants with IBD-PD in addition to several other variants as potential contributors to increased or decreased IBD-PD risk. SKAT-O identified two significant genes, LRRK2 and IL10RA, and NHC identified 6 significant gene clusters that are biologically relevant to IBD-PD. We observed prominent overlaps between the enriched pathways in the known IBD, PD, and candidate IBD-PD gene sets. Additionally, we detected significantly enriched pathways unique to the IBD-PD, including MAPK signaling, LPS/IL-1 mediated inhibition of RXR function, and NAD signaling. Fourteen final candidate IBD-PD genes were prioritized by biological relatedness methods. The biological importance scores estimated by protein-protein interaction networks and pathway and ontology enrichment analyses indicated the involvement of genes related to immunity, inflammation, and autophagy in IBD-PD. Additionally, PheWAS provided support for the associations of candidate genes with IBD and PD. CONCLUSIONS: Our study confirms and uncovers new LRRK2 associations in IBD-PD. The identification of novel inflammation and autophagy-related genes supports and expands previous findings related to IBD-PD pathogenesis, and underscores the significance of therapeutic interventions for reducing systemic inflammation.
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Comorbidade , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doenças Inflamatórias Intestinais/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Feminino , Masculino , Mutação de Sentido Incorreto , Estudo de Associação Genômica Ampla , Variação Genética , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVE: This study investigated the safety and efficacy of sclerotherapy with intralesional bleomycin injection (IBI) for retrobulbar orbital low-flow vascular lesions under multi-slice computed tomography (CT) guidance. METHODS: Between January 2010 and September 2021, consecutive patients with retrobulbar orbital low-flow vascular lesions who underwent CT-guided IBI at a tertiary centre in Taiwan were enrolled. Their medical records and imaging data were retrospectively collected. RESULTS: This study enrolled 13 patients (7 male and 6 female patients; age range: 1-57 years; mean age: 25.9 years) with lymphatic malformation (LM, n = 4), venolymphatic malformation (n = 1), and venous malformation (VM, n = 8). The overall radiological response rate was 76.9% (10 of 13); the radiological response rate was 75.0% in the VM group (6 of 8) and 75.0% in the LM group (3 of 4). Moreover, 3 patients (23.1%) had minor complications and 1 (7.7%) had a major complication. The mean clinical and radiological follow-up was 8.3 months and no recurrence or progression was reported. CONCLUSION: CT-guided IBI is an effective and relatively safe minimally invasive treatment for retrobulbar orbital low-flow vascular lesions, with an overall radiological response rate of 76.9% in a mean of 1.5 sessions and a low complication rate. ADVANCES IN KNOWLEDGE: CT-guided sclerotherapy with IBI is a relatively safe, effective, and feasible alternative treatment option for retrobulbar orbital low-flow vascular lesions.
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Bleomicina , Escleroterapia , Humanos , Feminino , Masculino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Injeções Intralesionais , Tomografia Computadorizada por Raios XRESUMO
Opium poppy, coca and cannabis are raw materials for three notorious illicit drugs. For a long time, drug lords have been growing and smuggling these drugs in a variety of ways and channels and are continually finding new ways of trafficking their wares, which has led to the increasing difficulty of global drug enforcement. In the present paper, we propose an innovative pollen identification system for these important drug plants, which provides a tool for screening and detection of the drugs to aid in drug enforcement. By utilizing the characteristics of these fine particles, their abundant production, and high resistance to decay, we believe this tool could be applied in the following scenarios: detecting and dynamically monitoring drug cultivation activities; determining whether a suspect has been to fields of drug plants and determining whether the site has ever been planted with a drug plant and/or was involved in drug production. In the future, combined with microscope automatic image acquisition technology and intelligent image recognition technology, this pollen identification system is expected to be used to screen three notorious illicit drug plants, thus enhancing the efficiency of drug related crime investigations.
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BACKGROUND: Our study aims to evaluate the genetic and phenotypic spectrum of Frontotemporal dementia (FTD) gene variant carriers in Chinese populations, investigate mutation frequencies, and assess the functional properties of TBK1 and OPTN variants. METHODS: Clinically diagnosed FTD patients underwent genetic analysis through exome sequencing, repeat-primed polymerase chain reaction, and Sanger sequencing. TBK1 and OPTN variants were biologically characterized in vitro using immunofluorescence, immunoprecipitation, and immunoblotting analysis. The frequencies of genes implicated in FTD in China were analyzed through a literature review and meta-analysis. RESULTS: Of the 261 Chinese FTD patients, 61 (23.4%) carried potential causative variants in FTD-related genes, including MAPT (n = 17), TBK1 (n = 7), OPTN (n = 6), GRN (n = 6), ANXA11 (n = 4), CHMP2B (n = 3), C9orf72 GGGGCC repeats (n = 2), CYLD (n = 2), PRNP (n = 2), SQSTM1 (n = 2), TARDBP (n = 2), VCP (n = 1), CCNF (n = 1), CHCHD10 (n = 1), SIGMAR1 (n = 1), CHCHD2 (n = 1), FUS (n = 1), TMEM106B (n = 1), and UBQLN2 (n = 1). 29 variants can be considered novel, including the MAPT p.D54N, p.E342K, p.R221P, p.T263I, TBK1 p.E696G, p.I37T, p.E232Q, p.S398F, p.T78A, p.Q150P, p.W259fs, OPTN p.R144G, p.F475V, GRN p.V473fs, p.C307fs, p.R101fs, CHMP2B p.K6N, p.R186Q, ANXA11 p.Q155*, CYLD p.T157I, SQSTM1 p.S403A, UBQLN2 p.P509H, CCNF p.S160N, CHCHD10 p.A8T, SIGMAR1 p.S117L, CHCHD2 p.P53fs, FUS p.S235G & p.S236G, and TMEM106B p.L144V variants. Patients with TBK1 and OPTN variants presented with heterogeneous clinical phenotypes. Functional analysis demonstrated that TBK1 I37T and E232Q mutants showed decreased autophosphorylation, and the OPTN phosphorylation was reduced by the TBK1 I37T mutant. The OPTN-TBK1 complex formation was enhanced by the TBK1 E696G mutant, while OPTN R144G and F475V mutants exhibited reduced recruitment to autophagosomes compared to the wild-type. The overall frequency of TBK1 and OPTN in Chinese FTD patients was 2.0% and 0.3%, respectively. CONCLUSIONS: Our study demonstrates the extensive genetic and phenotypic heterogeneity of Chinese FTD patients. TBK1 mutations are the second most frequent cause of clinical FTD after MAPT in the Chinese.
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Proteínas de Ciclo Celular , Demência Frontotemporal , Proteínas de Membrana Transportadoras , Proteínas Serina-Treonina Quinases , Fator de Transcrição TFIIIA , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Ciclo Celular/genética , China/epidemiologia , População do Leste Asiático/genética , Demência Frontotemporal/genética , Predisposição Genética para Doença/genética , Proteínas de Membrana Transportadoras/genética , Mutação , Proteínas Serina-Treonina Quinases/genética , Fator de Transcrição TFIIIA/genéticaRESUMO
CONTEXT: Sugar alcohols (also called polyols) are regarded as a "healthy" sugar substitute. One of the possible reasons for their safe use in pregnant women is their natural origin and the presence of polyols in maternal and fetal samples during normal human gestation. But little is known about the association between circulating sugar alcohols levels and maternal metabolic disorders during pregnancy. OBJECTIVE: We aimed to detect the concentration of the polyols in participants with and without gestational diabetes mellitus (GDM), and to investigate the association between maternal serum levels of polyols and GDM, as well as newborn outcomes. METHODS: A nested population-based case-control study was conducted in 109 women with and without GDM. Maternal concentrations of serum erythritol, sorbitol, and xylitol in the fasting state were quantified using a time of flight mass spectrometry system. RESULT: In women with GDM, serum concentrations of erythritol and sorbitol were higher, but serum concentrations of xylitol were lower than those in women without GDM. Per 1-SD increment of Box-Cox-transformed concentrations of erythritol and sorbitol were associated with the increased odds of GDM by 43% and 155% (95% CI 1.07-1.92 and 95% CI 1.77-3.69), while decreased odds were found for xylitol by 25% (95% CI 0.57-1.00). Additionally, per 1-SD increase of Box-Cox-transformed concentrations of serum sorbitol was associated with a 52% increased odds of large for gestational age newborns controlling for possible confounders (95% CI 1.00-2.30). CONCLUSION: Maternal circulating sugar alcohols levels during pregnancy were significantly associated with GDM. These findings provide the potential roles of polyols on maternal metabolic health during pregnancy.
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Diabetes Gestacional , Polímeros , Sorbitol , Humanos , Feminino , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Gravidez , Estudos de Casos e Controles , Adulto , Sorbitol/sangue , Recém-Nascido , Eritritol/sangue , Xilitol/sangueRESUMO
Biological invasions pose a significant threat to ecosystems, disrupting local biodiversity and ecosystem functions. The genomic underpinnings of invasiveness, however, are still largely unknown, making it difficult to predict and manage invasive species effectively. The common reed (Phragmites australis) is a dominant grass species in wetland ecosystems and has become particularly invasive when transferred from Europe to North America. Here, we present a high-quality gap-free, telomere-to-telomere genome assembly of Phragmites australis consisting of 24 pseudochromosomes and a B chromosome. Fully phased subgenomes demonstrated considerable subgenome dominance and revealed the divergence of diploid progenitors approximately 30.9 million years ago. Comparative genomics using chromosome-level scaffolds for three other lineages and a previously published draft genome assembly of an invasive lineage revealed that gene family expansions in the form of tandem duplications may have contributed to the invasiveness of the lineage. This study sheds light on the genome evolution of Arundinoideae grasses and suggests that genetic drivers, such as gene family expansions and tandem duplications, may underly the processes of biological invasion in plants. These findings provide a crucial step toward understanding and managing the genetic basis of invasiveness in plant species.
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Cromossomos de Plantas , Evolução Molecular , Genoma de Planta , Espécies Introduzidas , Poaceae , Poaceae/genética , Cromossomos de Plantas/genética , Filogenia , Genômica/métodosRESUMO
Fuchs endothelial corneal dystrophy (FECD) stands as the most prevalent primary corneal endothelial dystrophy worldwide, posing a significant risk to corneal homeostasis and clarity. Corneal endothelial cells exhibit susceptibility to oxidative stress, suggesting a nuanced relationship between oxidant-antioxidant imbalance and FECD pathogenesis, irrespective of FECD genotype. Given the constrained availability of corneal transplants, exploration into non-surgical interventions becomes crucial. This encompasses traditional antioxidants, small molecule compounds, biologics, and diverse non-drug therapies, such as gene-related therapy, hydrogen therapy and near infrared light therapy. This review concentrates on elucidating the mechanisms behind oxidant-antioxidant imbalance and the evolution of strategies to restore oxidant-antioxidant balance in FECD. It provides a comprehensive overview of both conventional and emerging therapeutic approaches, offering valuable insights for the advancement of non-surgical treatment modalities. The findings herein might establish a robust foundation for future research and the therapeutic strategy of FECD.
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Ovarian cancer is the tumor with the highest mortality among gynecological malignancies. Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages (TAMs) in the microenvironment. Colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) plays a key role in regulating the number and differentiation of macrophages in certain solid tumors. There are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tumor microenvironment. Here, we explored the antitumor efficacy and possible mechanisms of the CSF - 1R inhibitor pexidartinib (PLX3397) when combined with the first-line chemotherapeutic agent paclitaxel in the treatment of ovarian cancer. We found that CSF-1R is highly expressed in ovarian cancer cells and correlates with poor prognosis. Treatment by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in vivo. Blockade of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.
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While low-dose computed tomography (LDCT) for lung cancer screening (LCS) has been recognized for its effectiveness in reducing lung cancer mortality, it often simultaneously leads to the detection of incidental findings (IFs) unrelated to the primary screening indication. These IFs present diagnostic and management challenges, potentially causing unnecessary anxiety and further invasive diagnostic procedures for patients. This review article provides an overview of IFs encountered in LDCT, emphasizing their clinical significance and recommended management strategies. We categorize IFs based on their anatomical locations (intrathoracic-intrapulmonary, intrathoracic-extrapulmonary, and extrathoracic) and discuss the most common findings. We highlight the importance of utilizing guidelines and standardized reporting systems by the American College of Radiology (ACR) to guide appropriate follow-ups. For each category, we present specific IF examples, their radiologic features, and the suggested management approach. This review aims to provide radiologists and clinicians with a comprehensive understanding of IFs in LCS for accurate assessment and management, ultimately enhancing patient care. Finally, we outline a few key aspects for future research and development in managing IFs.
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Aedes albopictus is an important vector of arboviruses and prefers small containers of stagnant water as oviposition sites. One of the mechanisms mosquitoes use to search for suitable oviposition sites is relying on odor cues from prospective sites and their surroundings. The genetic and molecular bases of this behavior are not known for Ae. albopictus. Oviposition site-searching behavior can be separated into 2 stages: container location and water detection. We applied a glue compound to the antennae and the maxillary palps of adult females to mask their ability to detect molecules that may guide them to preferred oviposition sites. Treatment of the antennae significantly reduces the location index (P < 0.001), indicating a decreased ability to find oviposition sites, whereas no significant difference was observed in mosquitoes with maxillary palps treated with the same glue compound (P > 0.05). The detection time, measured as the duration from contact with the water surface to the deposition of the first egg, was extended in mosquitoes with treated antennae or maxillary palps, supporting the conclusion that olfaction is involved in the detection of oviposition site. Transcriptomic analysis identified differentially expressed olfactory-related genes, including obp67, obp56d-like, obp19d-like and obp67-like. RNA interference (RNAi)-mediated knockdown of obp67 and obp56d-like significantly affected the location index and detection time, respectively. Cas9/guide RNA-mediated knockout of obp56d-like resulted in a prolonged detection time, compared with the wild type (P < 0.05). These findings help to elucidate aspects of the olfactory mechanisms involved in Ae. albopictus oviposition site selection, and provide a basis for the development of mosquito surveillance and control strategies.
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Objective: Incomplete occlusion of cerebral dural arteriovenous fistula (DAVF) may lead to fistula recurrence and rebleeding, which may necessitate several embolizations and lead to worse clinical outcomes. Herein, we describe a grouting technique for endovascular embolization and its outcomes in a series of patients with complex intracranial DAVF. Methods: A total of 20 patients with aggressive type or symptomatic intracranial non-cavernous DAVF underwent endovascular transvenous embolization combining detachable coils and Onyx. Two microcatheters were positioned either in the distal segment of the involved sinus or near the draining veins. To achieve tight occlusion of the involved sinus, coils were carefully delivered through the first microcatheter, starting from the distal segment and then to the proximal segment. Next, Onyx was injected through the second microcatheter to reinforce and fill (grout) the interspace of coil mass and gradually refluxed to the mural channels and para-sinus cortical veins until the fistula was completely occluded. Results: Successful embolization was achieved in all 20 patients. The initial angiographic results revealed the achievement of complete occlusion in 19 patients (95%). At the postembolization follow-up, complete obliteration of the fistula was achieved in all patients (100%). No symptom or angiographic recurrence was observed at the 2- to 5-year follow-ups. No patient required additional embolization or stereotactic radiosurgery. Conclusion: The proposed grouting technique combining detachable coils and Onyx appears to be promising for the elimination of complex intracranial non-cavernous DAVFs.
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Corneal neovascularization (CNV) is a major cause of blindness worldwide. However, the recent drug treatment is limited by repeated administration and low drug bioavailability. In this work, SU6668 (an inhibitor of receptor tyrosine kinases) and indocyanine green (ICG) are loaded onto poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and then coated with anti-VEGFR2 single chain antibody (AbVr2 scFv) genetically engineered cell membrane vesicles. The nanomedicine is delivered via eye drops, and the hyperthermia induced by laser irradiation could block the blood vessels. Meanwhile, the photothermal effect can also cause the degradation of nanomaterials and release chemotherapeutic drugs in the blocked area, thereby continuously inhibit the neovascularization. Furthermore, SU6668 could inhibit the expression of heat shock protein 70 (HSP70), promoting the cell death induced by photothermal effect. In conclusion, the combination of photothermal and chemotherapy drugs provides a novel, effective and safe approach for the treatment of CNV.
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The vast majority of all global species have circadian rhythm cycles that allow them to adapt to natural environments. These regular rhythms are regulated by core clock genes and recent studies have also implicated roles for microRNAs in this regulation. Oviposition is an important circadian behavior in the reproductive cycle of insect vectors of diseases, and little is known about the rhythm or its regulation in mosquitoes. Aedes albopictus is a diurnal mosquito that transmits arboviruses and is the major cause of outbreaks of dengue fever in China. We analyzed the oviposition rhythm patterns of A. albopictus under different light/dark conditions and show that the mosquitoes have an oviposition peak between zeitgeber time 9 (ZT 9) and ZT 12. Furthermore, the antagomir-mediated knockdown of expression of the microRNA miR-2940-1 affected the oviposition rhythm of A. albopictus. These data support the conclusion that miR-2940-1 is involved in the regulation of oviposition rhythm in A. albopictus and provide a foundation for using oviposition rhythms as a new target for vector mosquito control.
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The potassium (K+) ion channel KCNK13 is specifically expressed in human microglia with elevated expression observed in post-mortem human brain tissue from patients with Alzheimer's disease. Modulation of KCNK13 activity by a small-molecule inhibitor is proposed as a potential treatment for neurodegenerative diseases. Herein, we describe the evolution of a series of KCNK13 inhibitors derived from a high-throughput screening campaign, resulting in CVN293, a potent, selective, and brain permeable clinical candidate molecule. CVN293 demonstrated a concentration-dependent inhibition of the NLRP3-inflammasome mediated production of IL-1ß from LPS-primed murine microglia. Cross-species pharmacokinetic data of CVN293 are also disclosed. These findings support the advancement of CVN293 in clinical trials.