Human induced pluripotent stem cells generate light responsive retinal organoids with variable and nutrient dependent efficiency

The availability of in vitro models of the human retina in which to perform pharmacological and toxicological studies is an urgent and unmet need. An essential step for developing in vitro models of human retina is the ability to generate laminated, physiologically functional and light-responsive retinal organoids from renewable and patient specific sources. We investigated five different human induced pluripotent stem cell (iPSC) lines and showed a significant variability in their efficiency to generate retinal organoids. Despite this variability, by month 5 of differentiation, all iPSC-derived retinal organoids were able to generate light responses, albeit immature, comparable to the earliest light responses recorded from the neonatal mouse retina, close to the period of eye opening. All iPSC-derived retinal organoids exhibited at this time a well-formed outer nuclear like layer containing photoreceptors with inner segments, connecting cilium and outer like segments. The differentiation process was highly dependent on seeding cell density and nutrient availability determined by factorial experimental design. We adopted the differentiation protocol to a multiwell plate format which enhanced generation of retinal organoids with retinal pigmented epithelium (RPE) and improved ganglion cell development and the response to physiological stimuli. We tested the response of iPSC-derived retinal organoids to Moxifloxacin and showed that similarly to in vivo adult mouse retina, the primary affected cell types were photoreceptors. Together our data indicate that light responsive retinal organoids derived from carefully selected and differentiation efficient iPSC lines can be generated at the scale needed for pharmacology and drug screening purposes. © AlphaMed Press 2018

Total Synthesis of (±)-Cafestol: A Late-Stage Construction of the Furan Ring Inspired by a Biosynthesis Strategy

An efficient bioinspired approach to the total synthesis of (±)-cafestol features a late-stage installation of the furan ring with a mild Au-catalyzed cycloisomerization. The Et₂AlCl-promoted aldehyde–ene cyclization and subsequent Friedel–Crafts reaction deliver a requisite tricyclic system in gram scale with high stereo- and regioselectivity. Moreover, a highly stereoselective SmI₂-mediated aldehyde–alkene radical cyclization furnishes the key bicyclo[3.2.1]­octane skeleton to offer an advanced intermediate for the synthesis of other oxygenated <i>ent</i>-kaurene diterpenoids

Data_Sheet_1_Mobile phone addiction is associated with impaired cognitive reappraisal and expressive suppression of negative emotion.DOCX

Previous studies have demonstrated people characterized by mobile phone addiction (MPA) are more prone to emotion regulation difficulties. However, no study has tested the effectiveness of their emotion regulation strategies in experimental conditions. In the present study, by instructing the MPA and control groups to regulate negative emotion through cognitive reappraisal (CR) or expressive suppression (ES), we compared their emotional states in the emotional visual search task after watching a negative emotion evoked video. A multi-factor mixed design of 2(group: MPA/control)×2(emotion regulation strategy: CR/ES)×3(image type: positive expression/negative expression/neutral expression) was conducted. We found the MPA group recognized the negative expression faster than control group after both emotion regulation strategies, indicating ES and CR were both impaired for MPA. The implications of these results were further discussed.</p

Stereoselective α‑Hydroxylation of Amides Using Oppolzer’s Sultam as Chiral Auxiliary

An Oppolzer’s sultam-based highly stereoselective α-hydroxylation of amides was developed to deliver the desired products in good yield and excellent diastereoselectivity (>20/1). The generally crystalline products and the recyclability of the chiral auxiliary illustrate the practicability and scalability of the current approach

A Chiral Pentenolide-Based Unified Strategy toward Dihydrocorynantheal, Dihydrocorynantheol, Protoemetine, Protoemetinol, and Yohimbane

An organocatalytic cross-aldol reaction of formaldehyde (formalin) with alkyl aldehydes, followed by the <i>Z</i>-selective Horner–Wadsworth–Emmons (HWE) reaction and immediate lactonization, afforded γ-alkylated pentenolides in good overall yields and excellent enantioselectivities. Based on this scalable sequence, five quinolizidine alkaloids were synthesized in a unified and concise manner. The development of an in situ activation of a tertiary amide to improve the efficiency of the Bischler–Napieraiski (B–N) reaction was also noteworthy due to the generality to sensitive substrates for a variety of target molecules

Data_Sheet_1_The durable effect of acupuncture for episodic migraine: a systematic review and meta-analysis.DOCX

BackgroundMigraine is a common and recurrent type of headache. Avoiding trigger factors is not often successful in reducing headache frequency, duration, and severity. Prophylactic medications may be effective but are limited by strict indications and daily medication intake. This review aimed to investigate the durable effect of acupuncture on episodic migraine.MethodsSeven databases including Medline, Embase, PubMed, etc., were searched for English and Chinese literature from their inception to 23 November 2022. Two independent reviewers screened the retrieved studies and extracted the data. Primary outcomes were monthly migraine days, monthly migraine attacks, and VAS score at 3 months post-treatment. The risk of bias in included studies was assessed using the Cochrane Risk of Bias 2.0 tool. Meta-analysis was conducted where applicable.ResultsFifteen studies were included in this review. Acupuncture reduced the number of migraine attacks (MD -0.68; 95% CI –0.93, −0.43; p ConclusionThis review found that the durable effect of acupuncture for episodic migraine lasted at least 3 months after treatment. More high-quality studies with longer follow-up periods in the future are needed to confirm the findings.</p

Confinement-Induced Deviation of Chain Mobility and Glass Transition Temperature for Polystyrene/Au Nanoparticles

The mobility and glass transition temperature (<i>T</i>_g) for polymers under nanoscale confinement differ substantially from the bulk. Whereas many studies have focused on the one-dimensional confinement, it has great significance to extend studies to higher geometries. Here, we systematically investigate the mobility by dipolar-filter sequence in solid-state NMR and <i>T</i>_g by DSC for thiolated polystyrene (PS-SH) on gold nanoparticles. The increase in <i>T</i>_g and signal suppression in NMR spectra clearly indicate that the surface confinement dominates molecular mobility as well as <i>T</i>_g. The molecular weight of PS-SH and nanoparticles size show significant influence on the immobilization and <i>T</i>_g. Our results can be fitted with a core–two shell model; the inner shell is under strong constraints while the outer shell with less confinement. This work is essential to better understand the confinement effect and also provides a step toward the ultimate desire to tailor the properties of nanomaterials

Catalytic Aza-Wacker Annulation: Tuning Mechanism by the Activation Mode of Amide and Enantioselective Syntheses of Melinonine‑E and Strychnoxanthine

An unprecedented N-substituent of the amide was found to be crucial for the successful annulation to establish 2-azabicyclo[3.3.1]­nonane and other ring skeletons in good yield. The novel catalytic aza-Wacker annulation methodology was further illustrated in the concise syntheses and the absolute configuration determinations of melinonine-E and strychnoxanthine

Investigation on the Mechanism of the Synthesis of Gold(I) Thiolate Complexes by NMR

In this article, we characterized the polymeric gold­(I) thiolates that precipitated from the intermediate solutions during the synthesis process of gold nanoparticles (GNPs) by the Brust–Schiffrin two-phase method and investigated the formation mechanism of the polymeric gold­(I) thiolates. The solution ¹H NMR confirmed the complete reduction from Au­(III) to Au­(I) with the addition of the first two equivalents of thiols, while only the third and fourth equivalents of thiols were found to participate in forming gold­(I) thiolates. Gold­(I) thiolates, [Au­(I)­SR]_<i>n</i>, precipitated from these solutions were further characterized by ¹H solid-state NMR spectroscopy under fast magic angle spinning (MAS), Raman spectroscopy, and thermogravimetric analysis. Further quantitative studies revealed that the composition of [Au­(I)­SR]_<i>n</i> could be controlled by changing the order of addition of the third and fourth equivalents of thiols. This work has great significance to better understand the mechanism of gold nanoparticle formation and thus to tailor the properties of the final products

Additional file 1: Figure S1. of Marker assisted pyramiding of Bph6 and Bph9 into elite restorer line 93–11 and development of functional marker for Bph9

Strategy used to pyramid Bph6 and Bph9 in 93–11 genetic background. Pokkali and Swarnalata are the resistance donors of Bph9 and Bph6, respectively. The resulting Bph6 and Bph9 pyramided line in 93–11 genetic background is designated as LuoYang69. (TIFF 330 kb