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Mouse epiblast and embryonic stem cells (mESCs) are considered to adhere strict lineage restriction and lack the potential to contribute to trophoectoderm (TE). In contrast, here we report the derivation of trophoblast stem cells (ESTS) from the mESCs. The single-cell transcriptome and molecular characterization of ESTS show similarity with TSCs. They efficiently integrate into the TE compartment of the blastocyst and contribute to the placenta during development. We discovered GSK3b signaling as the primary barrier for TE potential of the ESCs. It plays a vital stage-specific function during ESTS derivation. b-CATENIN and an intron-I regulatory element of Cdx2 were found to be essential for priming the ESCs to TE fate. We further show that the mouse epiblast possesses developmental plasticity and can readily differentiate into TE lineage. In contrast to the paradigm of the restricted potential of pluripotent ESCs and epiblast, our data shows that murine ESCs and epiblast have the unrestrained developmental potential for extraembryonic lineages.

SUMMARYmESCs and epiblast are considered to follow strict lineage adherence and lack the potential to contribute to trophoectoderm. Here, we report the derivation of trophoblast stem cells (ESTS) from the mESCs. The single-cell transcriptome and molecular characterization of ESTS show similarity with TSCs. They efficiently integrate into the TE compartment of the blastocyst and contribute to the placenta during development. We discovered GSK3β as a critical regulator of the TE fate of ESCs. It plays a vital stage-specific role during ESTS derivation. We further show β-CATENIN and an intron-I regulatory element ofCdx2are essential for the TE fate of ESCs. We further show that the mouse epiblast can readily differentiate into TE lineage. In contrast to the paradigm of the restricted potential of pluripotent ESCs and epiblast, our data shows that murine ESCs and epiblast have the unrestrained developmental potential for extraembryonic lineages.

SummaryHuman pluripotent stem cells (hPSCs) can self-organize into a blastocyst-like structure (blastoid) by virtue of their full developmental potential. The pluripotent mouse embryonic stem cells (mESC) are considered to lack this potential and hence can form blastoids only when combined with trophoblast stem cells. We performed a small molecule and cytokine screen to demonstrate that mESC have full potential to efficiently self-organize themselves into E-blastoids (ESC-blastoids). The morphology, cell lineages and the transcriptome of these blastoids resemble the mouse blastocyst. The E-blastoids undergo implantation andin uterodevelopment in mice. The transient reactivation of the 2C-gene network by retinoid signaling is essential for E-blastoid generation. GSK3β activity is critical for retinoid signaling and consequent 2C gene network activation. Collectively, the mESC possess full developmental potential to generate blastoids similar to hPSCs and other mammals. The plasticity of PSCs to self-organize into blastoids is not exclusive to humans or larger mammals; rather, it could be a general feature shared by most mammals, including rodents.

The self-renewal and differentiation potential of embryonic stem cells (ESCs) is maintained by the regulated expression of core pluripotency factors. Expression levels of the core pluripotency factor Nanog are tightly regulated by a negative feedback autorepression loop. However, it remains unclear how ESCs perceive NANOG levels and execute autorepression. Here, we show that a dose-dependent induction of Fgfbp1 and Fgfr2 by NANOG activates autocrine-mediated ERK signaling in Nanog-high cells to trigger autorepression. pERK recruits NONO to the Nanog locus to repress transcription by preventing POL2 loading. This Nanog autorepression process establishes a self-perpetuating reciprocal NANOG-pERK regulatory circuit. We further demonstrate that this reciprocal regulatory circuit induces pERK heterogeneity and ERK signaling dynamics in pluripotent stem cells. Collectively our data suggest that NANOG induces Fgfr2 and Fgfbp1 to activate ERK signaling in Nanog-high cells to establish a NANOG-pERK reciprocal regulatory circuit. This circuit regulates ERK signaling dynamics and Nanog autoregulation in pluripotent cells.

This paper is an effort to assemble in a synchronized manner, the brilliant contribution of the illustrious Keralian Mathematician and Astronomers, since Vararuchi (fourteenth century C.E) to Medieval Periods Madhava (C.1340- 1425), Paramesvara (C.1360- 1455), Nilakantha Somayaji (C. 1444 -1545) and his followers. It would entail that Indian Mathematics was well ahead by 350 to 400 years in comparison to European contributors Newton, Leibnitz, Taylor and others.

Colloidal nanoparticles with a magnetic–fluorescent property and varied surface chemistry have enormous biomedical application potential. However, the synthesis of a high quality of such a nanopart...

The self-renewal and differentiation potential of Embryonic stem cells (ESCs) is maintained by the regulated expression of core pluripotency factors. The expression level of core pluripotency factor Nanog is tightly regulated by a negative feedback autorepression loop. However, it remains unclear how the ESCs perceive the NANOG levels and execute autorepression. Here, we show that a dose-dependent induction of Fgfbp1 and Fgfr2 by NANOG activates an autocrine mediated ERK signaling in high-Nanog cells to trigger autorepression. pERK recruits NONO to Nanog locus to repress transcription by preventing POL2 loading. The Nanog autorepression process establishes a self-perpetuating NANOG-pERK reciprocal regulatory circuit. We further demonstrate that the reciprocal regulatory circuit induces the pERK heterogeneity and ERK signaling dynamics in pluripotent stem cells.

Luminescent materials possessing both the mechanoluminescence (MCL) and electroluminescence (EL) properties are the quest for sensing and optoelectronic applications. We report on the synthesis of a new tailor-made luminogen, 1,2-bis(4-(1-([1,1'-biphenyl]-4-yl)-2,2-diphenylvinyl)phenyl)-1,2-diphenylethene (TPE 5), using Suzuki coupling reaction with high yield. An aggregation-induced emission (AIE) active complex TPE 5 forms supramolecular spherical aggregates at the air-water interface of a Langmuir trough. As a consequence, a large enhancement of luminescence is obtained from the mono- and multilayer Langmuir-Blodgett films of TPE 5 owing to the AIE effect. The luminogen TPE 5 exhibits a reversible MCL response, displaying photoluminescence switching due to change in the crystalline states under external stimuli. The unique feature of luminescence enhancement upon aggregate formation is utilized for the fabrication of light-emitting diodes with low threshold voltage using supramolecular aggregates as the active layer. This work demonstrates an efficient strategy for obtaining controlled supramolecular aggregates of AIEgen with a potential in the dual applications of MCL and EL.

Caudal-type homeobox 2 (.Cdx2) transcription factor is an essential regulator of differentiation to the intestinal epithelium, somatic mesoderm and trophectoderm function in the mouse. However, the regulation of Cdx2 in these processes is poorly understood. Separation of viable Cdx2 expressing cells during differentiation for downstream experiments is not possible due to its nuclear localization, limiting experimental possibilities and studying Cdx2 regulation. Here, we report generation of a Cdx2-mCherry knock-in reporter mouse embryonic stem cell line (TCMC), for modeling and studying in vitro differentiation of mESCs to intestinal epithelia, somatic mesoderm, and trophectoderm.

An unambiguous synthesis of dichromeno[2,3-b;3′,2′-e]pyridine-12,14-diones has been developed under mild conditions and their optical properties have been evaluated by studying UV-vis absorption and photoluminescence (PL) spectroscopy, cyclic voltammetry (CV) measurements, DFT calculations and thermogravimetric analysis.

Four new donor–acceptor based stilbene derivatives were synthesized via Heck coupling reaction. These materials are green light emitters with good fluorescence quantum yield. Furthermore, the emitters show well matched HOMO/LUMO value as bipolar molecule. In addition, they are highly thermally stable. Optimized structures and electronic distribution in ground state are also studied to understand photophysical properties using DFT calculation. Keywords: Quinoxaline, Triphenylamine, Stilbene, Bipolar, Green light emitters

Aggregation induced emission (AIE) active molecules are widely used for fluorescence “turn-on” detection applications with the unique advantages over conventional fluorescent probes. Transformation of AIE molecule into functional nanoparticle can greatly expand their biomedical application potential. Here we report an approach for preparation of 20–80 nm size functional nanoparticle made of AIE molecule. The approach involves aggregation of AIE active tetraphenylethene (TPE) molecule in the presence of functional TPE molecule. Following this approach we have synthesized TPE-based nanoparticle functionalized with polyethylene glycol, primary amine, aspartic acid, glucose, and arginine. Compared to reported methods of making AIE-based nanoparticles, presented nanoparticles have distinct advantages that they are composed of AIE molecules only (without any non-AIE molecule/polymer) and wide variety of surface functionalization can be achieved by this approach. Nanoparticles have good colloidal stability with ...

Amyloid protein fibrillation is associated with a variety of neurodegenerative and other diseases, and their efficient detection and monitoring can greatly advance early diagnosis and therapy. Herein, we report a fluorescent "switch-on" probe for the reliable detection and monitoring of amyloid fibrils. The probe consists of a peptide component for binding with amyloid structure and a color component with an aggregation-induced green emission property. This probe is nonfluorescent in the presence of amyloid forming monomer protein/peptide, but fluorescence "switch-on" occurs after binding with amyloid fibrils. Compared to conventionally used thioflavin T, this probe offers a high signal-to-noise ratio, which is unaffected by the quencher ion/nanoparticle. The proposed new probe has been used for the detection and monitoring of amyloid fibrils produced by a wide variety of amyloid protein/peptides and can be extended for in vitro diagnostic applications.

A Public-Private Partnership (PPP) is a government service or private business venture which is funded and operated through a partnership of government and one or more private sector companies. Public-Private Partnerships and Collaboration (PPPs and PPC) in the Health Sector is important and timely in light of the challenges the public sector is facing in healthcare finance, management, and provision. PPPs and PPC in the health sector can take a variety of forms with differing degrees of public and private sector responsibility and risk but are characterized by various similarities as well. In our country, with regard to health care, the main responsibility is that of the state which aims to provide free access to health care system to all sections of the society. But a look at the health infrastructure of our country shows that in rural areas, in particular, there is insufficient infrastructure, be it hospitals, primary health care systems, ambulances etc. Hence, the urgent need of the government is to immediately take measures that will help to develop a basis to provide the needed medical support to all. Although the private sector is inequitable and expensive with over-application of clinical/operational procedures, it is perceived to be easily accessible, better managed and more efficient than its public counterpart. It is expected that PPP model in the sector will prove the success story of Indian health care system.

Aggregation behavior of luminophores is a subject of great interest over more than half a century. Aggregation generally causes quenching of luminescence of luminophores, which is detrimental for the solid state electroluminescence device fabrication. In oppose to the aggregation caused quenching, aggregation-induced emission phenomenon leads to highly luminescence state of luminophores upon aggregate formation. However, aggregation-induced emission behavior of the luminophores is commonly observed in irregular bulk solids, by adding antisolvents into a solution or in the biological cells, where the state of aggregation remains uncontrolled. Here we report on the synthesis of a new tailor made luminogen, 4′,4‴-(2,2-bis(4-methoxyphenyl)ethene-1,1-diyl)bis([1,1′-biphenyl]-4-carbaldehyde) (TPE 2) using Suzuki coupling reaction with high yield. We form the well-controlled supramolecular aggregates of TPE 2 ​at the air−water interface of a Langmuir trough. As a consequence, the mono- and multilayer Langmuir−Blodgett films of TPE 2 show a large enhancement of luminescence in comparison to the solution phase owing to the aggregation-induced emission phenomenon. We reveal inherent interaction of TPE 2 complexes within the supramolecular aggregates using density functional theory. This unique feature of luminescence enhancement is utilized for the fabrication of light-emitting diodes with low threshold voltage using TPE 2 as active layer. This study opens up the advantage of ordered supramolecular assembly to achieve optimal luminescence performances.

Three new oligophenylenevinylene (OligoPV)-cored luminogens were synthesized by utilizing the Suzuki coupling/Buchwald–Hartwig amination reaction and their aggregation-induced emission properties have been studied. Out of three, two are aggregation-induced emission enhancement (AIEE)-active molecules: weakly fluorescent in solution, while highly emissive in the aggregation state. The presence of the OligoPV core has turned an aggregation-caused quenching (ACQ) luminophore into an AIEE one. They show excellent solubility in common organic solvents, emit light in the green region (500–516 nm) and have high thermal stability.

Three new hexaphenylbenzene end-capped tri(p-phenylenevinylenes) were synthesized by the Horner–Wadsworth–Emmons reaction in good yields (86–76%). All compounds have bright fluorescent emissions in the blue to blue–green region in solution (λmax = 445–492 nm in tetrahydrofuran) and also high emission efficiency (Φfl = 0.51–0.72 in tetrahydrofuran). They exhibit good electrochemical reversibility, high thermal stability, and have high HOMO value.

Four new gem-tetraphenylethylene-based oligomers were synthesized by Suzuki coupling reaction in good yields (62–80%) and characterized by NMR, mass spectrometer and elemental analysis. The absorption maxima of the synthesized oligomers in the solution possess similar absorption bands located at 328–332 nm. They are shown to be thermally stable and emit light in blue region (404–485 nm). All the oligomers are AIE-active, emit weakly in solutions with Φf values not exceeding 4%, become strong emitters in the aggregated states and the PL intensity values increase up to 18-fold. The results of CV measurements of the oligomers showed good reversibility, indicating that the compounds have good electrochemical stability. The HOMO values of the oligomers are in the range of −5.63 to −5.61 eV. The photoluminescence properties in aggregate-state and the high HOMO energy levels of these oligomers make them applicable as an active material for a light-emitting device.

Three new tetraphenylethylene based oligomers bearing triphenylethylene moiety were synthesized utilizing Suzuki coupling reaction and their aggregation-induced emission properties were studied. They show excellent solubility in common organic solvents and emit light in blue region (440−504 nm). AIE effect is predominant for tetra-substituted TPE (20.1-fold) than mono-substituted one (4.5-fold).

A new series of V-shaped pyridine-cored π-conjugated oligomers are synthesized utilizing two-fold Heck/Suzuki coupling reactions. Optical properties of these compounds ( λ max =390–449 nm, Φ fl =79–5%, in solutions) are discussed. They are shown to be thermally stable and soluble in common organic solvents. Stilbenoid oligomers exhibited much higher fluorescence quantum yields than tri- and tetra-phenylethylene substituted oligomers in solutions.

Two novel star-shaped π-conjugated oligomers bearing a triphenylpyridine moiety as peripheral units and triphenylamine as a core have been synthesized via the threefold Heck/Sonogoshira coupling reaction protocol and their absorption and fluorescence properties have been examined. These oligomers showed excellent solubility in common organic solvents, emit light in blue and violet regions, and have high thermal stability.

Two new conjugated dendrimers bearing a tetraphenylethylene moiety as dendrons and triphenylamine as a core have been synthesized through a convergent synthetic strategy using threefold Heck/threefold Sonogashira coupling reaction. These dendrimers showed excellent solubility in common organic solvents and emit light in the blue and violet regions.

Four pyrene–vinyl–tetraphenylethylene based conjugated materials were synthesized and characterized by FT-IR, NMR, and mass spectroscopy. The photophysical (including absorption, fluorescence, and fluorescence lifetime) and aggregation properties in tetrahydrofuran were investigated. The photophysical and aggregation behavior depends on the spacer, substituent, and also the architecture (mono or tetra-branched) of the molecule. The vinyl spacer mono-branched compound is aggregation induced emission (AIE) active (αAIE = ∼6). Vinyl spacer tetra-branched compounds are AIE inactive, but their emitting efficiency is good in both solution (Φfl = 63%) phase and in the aggregated state (Φfl = 43%). Phenylvinyl spacer tetra-branched compounds emit light strongly in solution (Φfl = 92%), but not in the aggregated state (Φfl = 8%). They are shown to be thermally stable and emit light in the green region (500–550 nm). The results of cyclic voltammetry measurements of these materials showed irreversible oxidation waves, and have high HOMO energy levels (−5.66 to −5.53 eV).

The study attempts to look into the status of financial literacy in the unorganized sector of Purba Medinipur district of West Bengal. The focus is to identify any degree of association between the different variables that represent demographic factors and the level of financial literacy. For having a heterogeneous sample representing different parts of the district, multistage sampling method has been applied. First, five blocks of Purba Medinipur district have been chosen, following which one village has been chosen from each of them. Then, ten respondents from each village have been interviewed with the help of a questionnaire. Fisher's Exact Test is used to examine the significance of the association between the two kinds of classification as the sample sizes are small.

Two new tetraphenylethylene-cored stilbenoid dendrimers have been efficiently prepared by fourfold Heck reaction with appropriate dendron molecules. The methodology permits highly trans-selective c...