Nocardioides imazamoxiresistens sp. nov. Isolated from the Activated Sludge.

A Gram-staining-positive actinomycete named YZH12T was isolated from the sediment of the Yangtze River in Nanjing, Jiangsu province, China. Cells were aerobic, non-spore forming, non-motile, short rod (0.4-0.6 × 0.5-1.0 µm) or coccus (0.4-0.6 µm in diameter). Colonies were circular, smooth, and beige to yellowish. Growth occurred at 15-42 °C (optimal 28 °C), pH 5.0-9.0 (optimal 7.0), and 0-10% (w/v) NaCl (optimal 2%). The strain could tolerate 1500 mg/L of imazamox. Strain YZH12T showed 98.7% 16S rRNA gene sequence similarity Nocardioides zeae JM-1068T and less than 97% similarities with other type strains in the genus Nocardioides. Phylogenetic analysis based on genome and 16S rRNA gene sequences indicated that strain YZH12T was phylogenetically affiliated to the genus Nocardioides and formed a subclade with N. zeae JM-1068T and N. alkalitolerans DSM 16699T. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between YZH12T and closely related type strain N. zeae JM-1068T were 79.9% and 35.2%, respectively. The major fatty acids (> 5%) were C18: 1ω9c, iso-C16: 0, C16: 0, C17: 1ω8cand C18: 0; the major respiratory quinone was MK-8(H4); and the polar lipids profiles were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), glycolipid (GL), two aminophospholipids (APL1, APL2), and an unknown polar lipid (L). The genomic DNA G + C content is 73.5%. Based on the phenotypic, chemotaxonomic, phylogenetic analyses, and genomic data, strain YZH12T represents a novel species of the genus Nocardioides, for which the name Nocardioides imazamoxiresistens YZH12T is proposed, with strain YZH12T (= KCTC 49964T = MCCC 1K0892T) as the type strain.

Diagnostic and Management Value of Multi-Slice Computed Tomography in Esophageal Jujube Pit Impaction.

Objective: The diagnostic value of multi-slice computed tomography (MSCT) in esophageal jujube pit impaction was explored in this study. Methods: A retrospective analysis was performed on MSCT data obtained from a cohort of 40 patients experiencing esophageal jujube pit impaction. The study period encompassed the interval from December 2018 to November 2019. The analysis involved examining the age distribution of the patients, the location of the jujube pit impaction, its connection to the esophagus, associated complications, and the methods used for treatment. All imaging results were compared with the outcomes of surgical or endoscopic interventions. Results: (1) Out of 40 patients, 30 individuals were 58 years old or above, constituting 75% of the study sample. (2) In 80% of the instances (32 cases), the jujube pit was located in the initial segment of the esophagus, exhibiting a spindle shape with varying levels of central low density. (3) We examined the correlation between the angle of the impacted jujube pit and the esophageal longitudinal axis, categorizing 2 cases as longitudinal impaction, 16 as oblique impaction, and 22 as transverse impaction. Among the 40 cases, 28 displayed only slight thickening of the esophageal wall at the impaction site, while 9 cases exhibited heightened periesophageal fat density, and 3 showed small periesophageal air bubbles. (4) Endoscopic evaluation identified damage to the esophageal mucosa in 35 instances and the formation of esophageal perforation in 5 cases. Among patients with perforation, one or both ends of the jujube pit had penetrated the esophageal wall, accompanied by different levels of surrounding inflammatory encapsulation. Conclusion: MSCT is crucial for pinpointing jujube pit impaction and its relation to the esophageal wall and nearby structures, aiding in preoperative and postoperative complications. It is highly feasible for endoscopic cases but limited in complex ones needing thoracoscopy or open-heart surgery.

Brain implantation of tissue-level-soft bioelectronics via embryonic development.

The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate 1,2 . These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development 3-9 . Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.

Assessment of coastal eco-environmental sustainable development under multiple pressures: A case study of Jiaozhou Bay, China.

The increasing demand for economic development in the coastal zone is exerting greater pressure on the eco-environment in this region. Therefore, it is imperative to conduct comprehensive research on the sustainable development of the eco-environment in coastal areas. Grounded in sustainable development theory and Integrated Coastal Zone Management (ICZM), this study assessed sustainable development of Jiaozhou Bay (JZB), China over the period from 2015 to 2019 under multiple pressures applying the Driver-Pressure-State-Impact-Response (DPSIR) framework. Subsequently, a SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis was employed to propose specific countermeasures and recommendations. In terms of weight within the criterion layer, Response (R) and Pressure (P) were assigned higher weights. The comprehensive assessment value Z in the target layer indicated a slight decrease in 2016 followed by a gradual increase that eventually led to stabilization. The comprehensive assessment values of the indicators varied depending on different conditions, implying that higher values would contribute to sustainable development of the eco-environment. Based on a SWOT analysis, strategies for Qingdao were derived from a combination of research findings and future development policy. These strategies include preventing and controlling land and sea pollution, governing reclamation activities, optimizing industrial structure, and strengthening public opinion guidance. This study highlights the application of quantitative and qualitative analysis methods in ICZM, providing specific recommendations based on policy analysis for achieving sustainable development in JZB's eco-environment under multiple pressures.

A new machine learning model to predict the prognosis of cardiogenic brain infarction.

Cardiogenic cerebral infarction (CCI) is a disease in which the blood supply to the blood vessels in the brain is insufficient due to atherosclerosis or stenosis of the coronary arteries in the patient's heart, which leads to neurological deficits. To predict the pathogenic factors of cardiogenic cerebral infarction, this paper proposes a machine learning based analytical prediction model. 494 patients with CCI who were hospitalized for the first time were consecutively included in the study between January 2017 and December 2021, and followed up every three months for one year after hospital discharge. Clinical, laboratory and imaging data were collected, and predictors associated with relapse and death in CCI patients at six months and one year after discharge were analyzed using univariate and multivariate logistic regression methods, meanwhile established a new machine learning model based on the enhanced moth-flame optimization (FTSAMFO) and the fuzzy K-nearest neighbor (FKNN), called BITSAMFO-FKNN, which is practiced on the dataset related to patients with CCI. Specifically, this paper proposes the spatial transformation strategy to increase the exploitation capability of moth-flame optimization (MFO) and combines it with the tree seed algorithm (TSA) to increase the search capability of MFO. In the benchmark function experiments FTSAMFO beat 5 classical algorithms and 5 recent variants. In the feature selection experiment, ten times ten-fold cross-validation trials showed that the BITSAMFO-FKNN model proved actual medical importance and efficacy, with an accuracy value of 96.61%, sensitivity value of 0.8947, MCC value of 0.9231, and F-Measure of 0.9444. The results of the trial showed that hemorrhagic conversion and lower LVDD/LVSD were independent risk factors for recurrence and death in patients with CCI. The established BITSAMFO-FKNN method is helpful for CCI prognosis and deserves further clinical validation.

Assembly of Heterocyclic C-Glycosides by Ru-Catalyzed C-H Activation/Cyclization with Carbonyl Sulfoxonium Ylide Glyco-Reagents.

New carbonyl sulfoxonium ylide glyco-reagents have been developed, enabling the synthesis of versatile heteroarene C-glycosides through a Ru-catalyzed C-H activation/annulation strategy. These reactions tolerate various saccharide donors and represent a significant advance in the stereoselective synthesis of heterocyclic C-glycosides. Furthermore, the strategy and methods could be applied to large-scale reactions and late-stage modifications of some structurally complex natural products or drugs.

Associations of mixed metal exposure with chronic kidney disease from NHANES 2011-2018.

Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear. We assessed the urine and whole blood levels of cadmium (Cd), manganese (Mn), lead (Pb), mercury (Hg), and renal function in 3080 adults from National Health and Nutrition Survey (NHANES) (2011-2018) to explore the effect of mixed metal exposure on CKD especially in people with type 2 diabetes mellitus (T2DM). Weighted quantile sum regression model and Bayesian Kernel Machine Regression model were used to evaluate the overall exposure impact of metal mixture and potential interaction between metals. The results showed that the exposure to mixed metals was significantly associated with an increased risk of CKD in blood glucose stratification, with the risk of CKD being 1.58 (1.26,1.99) times in urine and 1.67 (1.19,2.34) times in whole blood higher in individuals exposed to high concentrations of the metal mixture compared to those exposed to low concentrations. The effect of urine metal mixture was elevated magnitude in stratified analysis. There were interactions between urine Pb and Cd, Pb and Mn, Pb and Hg, Cd and Mn, Cd and Hg, and blood Pb and Hg, Mn and Cd, Mn and Pb, Mn and Hg on the risk of CKD in patients with T2DM and no significant interaction between metals was observed in non-diabetics. In summary, mixed metal exposure increased the risk of CKD in patients with T2DM, and there were complex interactions between metals. More in-depth studies are needed to explore the mechanism and demonstrate the causal relationship.

An investigation of the prevalence and diversity of Anisakis in China: marine food safety implications.

Anisakis can cause Anisakiasis in humans if raw or undercooked fish is consumed. Symptoms of infection may include vomiting, acute abdominal symptoms, or allergies. In this study, we collected 187 commercially available marine fish from the Yellow Sea, East China Sea, and South China Sea. Among them, 79 were found positive containing 520 Anisakis worms. The average prevalence rate was found 42% in this investigation. Ninety-two worms from different sea areas were selected and analyzed for identification, revealing the presence of five different species, which are Anisakis pegreffii, Hysterothylacium aduncum, Hysterothylacium zhoushanense, Hysterothylacium amoyense, and Hysterothylacium sp. In the meta-analysis, three databases: PubMed, CNKI, and BaiduXueshu were searched for surveys on the prevalence of Anisakis in Chinese waters from January 2000 to December 2023. A total of 26 studies were included in this analysis of which 25 publications were retrieved from different databases and one being the present study. The pooled prevalence of Anisakis was 45% among commercially available marine fish. Variances in the prevalence of Anisakis were noted among the four seas, with the highest rates in the East China Sea and the Bohai Sea, reaching 53% [0.38; 0.68] and 49% [0.36; 0.62], respectively. The Prevalence of Anisakis infection was significantly higher in astern parts such as Liaoning, Shanghai, and Zhejiang. Analysis of the host fish subgroups revealed that the orders of Anguilliformes, Scombriformes, and Gadiformes had high rates of infection. These findings suggest a significant prevalence of Anisakis, posing an increasing risk of infection for individuals. This study provides impactful information for implementing preventative measures against Anisakis.

YTHDF2 regulates MSS51 expression contributing to mitochondria dysfunction of granulosa cells in polycystic ovarian syndrome patients.

RESEARCH QUESTION: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients? DESIGN: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition. RESULTS: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM. CONCLUSIONS: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients.

Analysis of microbial community composition and diversity in the rhizosphere of Salvia miltiorrhiza at different growth stages.

Salvia miltiorrhiza is a kind of medicinal plant with various pharmacological activities. Few studies on the composition and diversity of rhizosphere microbial communities at different growth stages have been conducted on Salvia miltiorrhiz; in particular, salviorrhiza grows in soil that has been continuously planted for 3 years. The purpose of this study was to understand the changes of soil physicochemical properties of Salvia miltiorrhiza at different growth stages, and to study the composition and diversity of rhizosphere microbial community at different growth stages. Illumina NovaSeq sequencing technology was used to analyze the bacterial 16S rRNA gene and the fungal ITS region in the rhizosphere soil of Salvia miltiorrhiza at different growth stages. The results showed that the dominant bacterial phyla in the Salvia miltiorrhiza rhizosphere were Proteobacteria, Bacteroidetes, Acidobacteria, Firmicutes, Actinobacteria, and Chloroflexi. The dominant fungal phyla were Ascomycota, Mortierellomycota, Basidiomycota, and Rozellomycota. During the growth of Salvia miltiorrhiza, the physical and chemical properties of soil changed. As the Salvia miltiorrhiza grew, the content of available phosphorus, available potassium, pH, nitrate nitrogen, and ammonium nitrogen significantly decreased. Ammonium nitrogen and nitrate nitrogen had a greater impact on the bacterial community structure in the rhizosphere than on the fungal community structure. The work was to reveal differences in the rhizosphere bacterial and fungal community structure during different growth stages of Salvia miltiorrhiza, further understand the changes of rhizosphere microbial ecological characteristics and soil physicochemical properties during the cultivation of Salvia miltiorrhiza.

The role of inflammation in central serous chorioretinopathy: From mechanisms to therapeutic prospects.

Central serous chorioretinopathy (CSC) is a leading cause of permanent vision loss, ranking fourth among macular diseases, trailing only age-related macular degeneration, diabetic retinopathy, and retinal vein obstruction. While mounting evidence implicates inflammation as a pivotal factor in the onset and advancement of CSC, the specific pathophysiological process and molecular mechanisms underlying inflammation remain incompletely understood. A complex network of cytokines, chemokines, and adhesion molecules interplay to trigger inflammatory and pathological cascades, highlighting the need for a comprehensive comprehension of the inflammation-related mechanisms behind CSC progression. In this piece, we examine the existing comprehension of CSC's pathology and pathogenesis. Additionally, we present an overview of the mechanisms underlying the onset and progression of CSC inflammation, followed by a thorough analysis and discussion of the potential of targeted inflammatory intervention for both preventing and treating CSC.

Therapeutic Potential of Essential Oils Against Ulcerative Colitis: A Review.

Ulcerative colitis (UC) is a chronic non-sp ecific inflammatory disease of the colorectal mucosa. Researchers have associated UC onset with familial genetics, lifestyle behavior, inflammatory immune factors, intestinal microbiota, and the integrity of the intestinal mucosal barrier. The primary therapeutic interventions for UC consist of pharmacological management to control inflammation and promote mucosal healing and surgical interventions. The available drugs effectively control and decelerate the progression of UC in most patients; nonetheless, their long-term administration can exert adverse effects and influence the therapeutic effect. Plant essential oils (EOs) refer to a group of hydrophobic aromatic volatile substances. EOs have garnered considerable attention in both domestic and international research because of their anti-inflammatory, antibacterial, and antioxidant properties. They include peppermint, peppercorns, rosemary, and lavender, among others. Researchers have investigated the role of EOs in medicine and have elucidated their potential to mitigate the detrimental effects of UC through their anti-inflammatory, antioxidant, antidepressant, and anti-insomnia properties as well as their ability to regulate the intestinal flora. Furthermore, EOs exert minimal toxic adverse effects, further enhancing their appeal for therapeutic applications. However, these speculations are based on theoretical experiments, thereby warranting more clinical studies to confirm their effectiveness and safety. In this article, we aim to provide an overview of the advancements in utilizing natural medicine EOs for UC prevention and treatment. We will explore the potential pathogenesis of UC and examine the role of EOs therapy in basic research, quality stability, and management specification of inadequate EOs for UC treatment. We intend to offer novel insights into the use of EOs in UC prevention and management.

Exploring the potential of Paris polyphylla var. yunnanensis pollen manipulation in modifying seed dormancy.

Paris polyphylla var. yunnanensis, a well-known Chinese medicinal herb, shows a unique physiological trait characterized by the cyclic opening and closing of its anthers after pollen maturation. The aim of this study was to explore the implications of this phenomenon on breeding. RNA sequencing coupled with methylation sequencing was used to scrutinize and compare gene expression profiles and methylation alterations in pollen and seeds during anther opening and closing, along with cold exposure. Genes enriched within Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were examined to identify gene clusters susceptible to temperature-related methylation changes in both pollen and seeds. Four pollen treatment models, namely, normal control, "pollen protected from low temperatures," "pollen from just-opened anther," and "pollen from close-blocked anther," were used to produce corresponding seeds via artificial pollination. Subsequently, qRT-PCR was used to validate modifications in the expression patterns of marker genes in pollinated seeds under diverse treatment scenarios. Genes exhibiting significant differences in expression between anthers and normal tissues, along with gene regions linked to methylation variations attributed to low-temperature-treated pollen and seeds, were identified through transcriptomic analysis. Convergence was observed in three signaling pathways: oxidative phosphorylation (ko00190), plant hormone signal transduction (Ko04075), and zeatin biosynthesis (ko00908). Notably, gene clusters prone to temperature-induced methylation changes, such as NADH-ubiquinone oxidoreductase chain 5, plasma membrane ATPase 4, cytochrome c oxidase subunit 2, cis-zeatin O-glucosyltransferase, ABSCISIC ACID-INSENSITIVE 5-like protein 4, and indole-3-acetic acid-amido synthetase (IAAS), were identified. Evaluation using various pollen pollination models revealed altered expression patterns of five dormancy-regulating marker genes: IAAS, sucrose synthase (SUS), gibberellin 2-oxidase (GA2ox), ABA INSENSITIVE 2 (ABI2), and auxin-repressed protein (ARP), in seeds pollinated with pollen from close-blocked anthers, cold-protected pollen, and pollen from freshly opened anthers. The close-blocked anther treatment led to significantly upregulated expression of IAAS, SUS, GA2ox, and ABI2, whereas ARP expression decreased markedly, indicating a propensity toward prolonged seed dormancy. Conversely, in the low-temperature-protected anther model, SUS, ARP, GA2ox, and IAAS exhibited reduced expression levels, whereas the expression of ABI2 was upregulated, overall facilitating seed germination.

Organocatalyzed Asymmetric Michael Addition of 3-Fluorooxindole to Vinylidene Bisphosphonates.

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

Invasive assessment of coronary microvascular dysfunction and cardiovascular outcomes across the full spectrum of CAD: a meta-analysis.

INTRODUCTION AND OBJECTIVES: Coronary microvascular dysfunction (CMD) is highly prevalent and is recognized as an important clinical entity in patients with coronary artery disease (CAD). Nevertheless, the association of CMD with adverse cardiovascular events in the spectrum of CAD has not been systemically quantified. METHODS: We searched electronic databases for studies on patients with CAD in whom coronary microvascular function was measured invasively, and clinical events were recorded. The primary endpoint was major adverse cardiac events (MACE), and the secondary endpoint was all-cause death. Estimates of effect were calculated using a random-effects model from published risk ratios. RESULTS: We included 27 studies with 11 404 patients. Patients with CMD assessed by invasive methods had a higher risk of MACE (RR, 2.18; 95%CI, 1.80-2.64; P < .01) and all-cause death (RR, 1.88; 95%CI, 1.55-2.27; P < .01) than those without CMD. There was no significant difference in the impact of CMD on MACE (interaction P value = .95) among different invasive measurement modalities. The magnitude of risk of CMD assessed by invasive measurements for MACE was greater in acute coronary syndrome patients (RR, 2.84, 95%CI, 2.26-3.57; P < .01) than in chronic coronary syndrome patients (RR, 1.77, 95%CI, 1.44-2.18; P < .01) (interaction P value < .01). CONCLUSIONS: CMD based on invasive measurements was associated with a high incidence of MACE and all-cause death in patients with CAD. The magnitude of risk for cardiovascular events in CMD as assessed by invasive measurements was similar among different methods but varied among CAD populations.

Big Decisions on Small Cell Lung Cancer: A Focus on Clinical Care Updates and Patient Perspectives.

Small cell lung cancer (SCLC) is an uncommon, aggressive high-grade neuroendocrine carcinoma, associated with tobacco use. It is a highly chemosensitive disease that initially responds quickly to systemic therapy, although patients with SCLC tend to develop relapse. Although the landscape of SCLC treatment has remained stagnant for many decades, the field has seen notable advances in the past few years, including the use of immunotherapy, the development of further lines of systemic therapy, the refinement of thoracic and intracranial radiotherapy, and-most recently-the promise of more targeted therapies. Patients with SCLC also must face unique psychosocial burdens in their experience with their cancer, distinct from patients with other lung cancer. In this article, we review the latest literature and future directions in the management and investigation of SCLC, as well as the critical decisions that providers and patients must navigate in the current landscape. We also present the perspectives of several patients with SCLC in conjunction with this summary, to spotlight their individual journeys in the context of this challenging disease.

Oyster mantle-derived exosomes alleviate osteoporosis by regulating bone homeostasis.

Osteoporosis is a major public health problem with an urgent need for safe and effective therapeutic interventions. The process of shell formation in oysters is similar to that of bone formation in mammals, and oyster extracts have been proven to exert osteoprotective effects. Oyster mantle is the most crucial organ regulating shell formation, in which exosomes play an important role. However, the effects of oyster mantle-derived exosomes (OMEs) on mammalian osteoporosis and the underlying mechanisms remain unknown. The OMEs investigated herein was found to carry abundant osteogenic cargos. They could also survive hostile gastrointestinal conditions and accumulate in the bones following oral administration. Moreover, they promoted osteoblastic differentiation and inhibited osteoclastic differentiation simultaneously. Further mechanistic examination revealed that OMEs likely promoted osteogenic activity by activating PI3K/Akt/ß-catenin pathway in osteoblasts and blunted osteoclastic activity by inhibiting NF-κB pathway in osteoclasts. These favorable pro-osteogenic effects of OMEs were also corroborated in a rat femur defect model. Importantly, oral administration of OMEs effectively attenuated bone loss and improved the bone microstructure in ovariectomy-induced osteoporotic mice, and demonstrating excellent biosafety. The mechanistic insights from our data support that OMEs possess promising therapeutic potential against osteoporosis.

Raddeanin A Protects the BRB Through Inhibiting Inflammation and Apoptosis in the Retina of Alzheimer's Disease.

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.

Acid-Promoted Multicomponent Reaction To Synthesize 4-Phosphorylated 4H-Chromenes.

An effective multicomponent reaction for the synthesis of 4-phosphorylated 4H-chromenes via a tandem phosphorylation/alkylation/cyclization/dehydration sequence with water as the only byproduct was developed. Extensive mechanistic investigations involving in situ NMR experiments, time control experiments, and in situ HRMS experiment allowed us to elucidate the order of each subreaction to arrive at a complete understanding of the underlying mechanism of this multicomponent reaction. Mechanistic data confirm that the reaction begins with a phospha-aldol-elimination, followed by addition of a ketone enolate, intermolecular alkylation, intramolecular cyclization, and dehydration under acidic conditions.