Development and characterization of human fetal female reproductive tract organoids to understand Müllerian duct anomalies.

Müllerian ducts are paired tubular structures that give rise to most of the female reproductive organs. Any abnormalities in the development and differentiation of these ducts lead to anatomical defects in the female reproductive tract organs categorized as Müllerian duct anomalies. Due to the limited access to fetal tissues, little is understood of human reproductive tract development and the associated anomalies. Although organoids represent a powerful model to decipher human development and disease, such organoids from fetal reproductive organs are not available. Here, we developed organoids from human fetal fallopian tubes and uteri and compared them with their adult counterparts. Our results demonstrate that human fetal reproductive tract epithelia do not express some of the typical markers of adult reproductive tract epithelia. Furthermore, fetal organoids are grossly, histologically, and proteomically different from adult organoids. While external supplementation of WNT ligands or activators in culture medium is an absolute requirement for the adult reproductive tract organoids, fetal organoids are able to grow in WNT-deficient conditions. We also developed decellularized tissue scaffolds from adult human fallopian tubes and uteri. Transplantation of fetal organoids onto these scaffolds led to the regeneration of the adult fallopian tube and uterine epithelia. Importantly, suppression of Wnt signaling, which is altered in patients with Müllerian duct anomalies, inhibits the regenerative ability of human fetal organoids and causes severe anatomical defects in the mouse reproductive tract. Thus, our fetal organoids represent an important platform to study the underlying basis of human female reproductive tract development and diseases.

Bovine and human endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues.

Organoid technology has provided unique insights into human organ development, function, and diseases. Patient-derived organoids are increasingly used for drug screening, modeling rare disorders, designing regenerative therapies, and understanding disease pathogenesis. However, the use of Matrigel to grow organoids represents a major challenge in the clinical translation of organoid technology. Matrigel is a poorly defined mixture of extracellular matrix proteins and growth factors extracted from the Engelbreth-Holm-Swarm mouse tumor. The extracellular matrix is a major driver of multiple cellular processes and differs significantly between tissues as well as in healthy and disease states of the same tissue. Therefore, we envisioned that the extracellular matrix derived from a native healthy tissue would be able to support organoid growth akin to organogenesis in vivo. Here, we have developed hydrogels from decellularized human and bovine endometrium. These hydrogels supported the growth of mouse and human endometrial organoids, which was comparable to Matrigel. Organoids grown in endometrial hydrogels were proteomically more similar to the native tissue than those cultured in Matrigel. Proteomic and Raman microspectroscopy analyses showed that the method of decellularization affects the biochemical composition of hydrogels and, subsequently, their ability to support organoid growth. The amount of laminin in hydrogels correlated with the number and shape of organoids. We also demonstrated the utility of endometrial hydrogels in developing solid scaffolds for supporting high-throughput, cell culture-based applications. In summary, endometrial hydrogels overcome a major limitation of organoid technology and greatly expand the applicability of organoids to understand endometrial biology and associated pathologies.

Accelerating Computational Materials Discovery with Machine Learning and Cloud High-Performance Computing: from Large-Scale Screening to Experimental Validation.

High-throughput computational materials discovery has promised significant acceleration of the design and discovery of new materials for many years. Despite a surge in interest and activity, the constraints imposed by large-scale computational resources present a significant bottleneck. Furthermore, examples of very large-scale computational discovery carried out through experimental validation remain scarce, especially for materials with product applicability. Here, we demonstrate how this vision became reality by combining state-of-the-art machine learning (ML) models and traditional physics-based models on cloud high-performance computing (HPC) resources to quickly navigate through more than 32 million candidates and predict around half a million potentially stable materials. By focusing on solid-state electrolytes for battery applications, our discovery pipeline further identified 18 promising candidates with new compositions and rediscovered a decade's worth of collective knowledge in the field as a byproduct. We then synthesized and experimentally characterized the structures and conductivities of our top candidates, the NaxLi3-xYCl6 (0≤ x≤ 3) series, demonstrating the potential of these compounds to serve as solid electrolytes. Additional candidate materials that are currently under experimental investigation could offer more examples of the computational discovery of new phases of Li- and Na-conducting solid electrolytes. The showcased screening of millions of materials candidates highlights the transformative potential of advanced ML and HPC methodologies, propelling materials discovery into a new era of efficiency and innovation.

In Situ Characterization of Metastable Pb3O5 and Pb2O3 Phases During Thermal Decomposition of PbO2 to PbO.

Nonstoichiometric lead oxides play a key role in the formation and cycling of the positive electrodes in a lead acid battery. These phases have been linked to the underutilization of the positive active material but also play a key role in the battery's cycle life, providing interparticle adhesion and the connection to the underlying lead grid. Similar phases have previously been identified by mass loss or color change during thermal annealing of PbO2 to PbO, suggesting that at least two intermediate PbOx phases exist. Using multiple, in situ analysis techniques (powder diffraction, X-ray absorption, X-ray photoelectron spectroscopy) and ex situ nuclear magnetic resonance measurements, the structural conversion and changes in the lead oxidation state were identified during this process. Isolation of the PbOx phases enabled confirmation of Pb3O5 and Pb2O3 by diffraction and the first 207Pb NMR measurement of these intermediates. The thermodynamic and kinetic stability of these intermediates and other reported polymorphs were determined by density functional theory, providing key insight into their origins and variation of PbOx structures found in previous studies.

Stimuli-Responsive Silica Silanol Conjugates: Strategic Nanoarchitectonics in Targeted Drug Delivery.

The design of novel drug delivery systems is exceptionally critical in disease treatments. Among the existing drug delivery systems, mesoporous silica nanoparticles (MSNs) have shown profuse promise owing to their structural stability, tunable morphologies/sizes, and ability to load different payload chemistry. Significantly, the presence of surface silanol groups enables functionalization with relevant drugs, imaging, and targeting agents, promoting their utility and popularity among researchers. Stimuli-responsive silanol conjugates have been developed as a novel, more effective way to conjugate, deliver, and release therapeutic drugs on demand and precisely to the selected location. Therefore, it is urgent to summarize the current understanding and the surface silanols' role in making MSN a versatile drug delivery platform. This review provides an analytical understanding of the surface silanols, chemistry, identification methods, and their property-performance correlation. The chemistry involved in converting surface silanols to a stimuli-responsive silica delivery system by endogenous/exogenous stimuli, including pH, redox potential, temperature, and hypoxia, is discussed in depth. Different chemistries for converting surface silanols to stimuli-responsive bonds are discussed in the context of drug delivery. The critical discussion is culminated by outlining the challenges in identifying silanols' role and overcoming the limitations in synthesizing stimuli-responsive mesoporous silica-based drug delivery systems.

Emerging Trends of Carbon-Based Quantum Dots: Nanoarchitectonics and Applications.

Carbon-based quantum dots (QDs) have emerged as a fascinating class of advanced materials with a unique combination of optoelectronic, biocompatible, and catalytic characteristics, apt for a plethora of applications ranging from electronic to photoelectrochemical devices. Recent research works have established carbon-based QDs for those frontline applications through improvements in materials design, processing, and device stability. This review broadly presents the recent progress in the synthesis of carbon-based QDs, including carbon QDs, graphene QDs, graphitic carbon nitride QDs and their heterostructures, as well as their salient applications. The synthesis methods of carbon-based QDs are first introduced, followed by an extensive discussion of the dependence of the device performance on the intrinsic properties and nanostructures of carbon-based QDs, aiming to present the general strategies for device designing with optimal performance. Furthermore, diverse applications of carbon-based QDs are presented, with an emphasis on the relationship between band alignment, charge transfer, and performance improvement. Among the applications discussed in this review, much focus is given to photo and electrocatalytic, energy storage and conversion, and bioapplications, which pose a grand challenge for rational materials and device designs. Finally, a summary is presented, and existing challenges and future directions are elaborated.

Metal nitride-based nanostructures for electrochemical and photocatalytic hydrogen production.

The over-dependence on fossil fuels is one of the critical issues to be addressed for combating greenhouse gas emissions. Hydrogen, one of the promising alternatives to fossil fuels, is renewable, carbon-free, and non-polluting gas. The complete utilization of hydrogen in every sector ranging from small to large scale could hugely benefit in mitigating climate change. One of the key aspects of the hydrogen sector is its production via cost-effective and safe ways. Electrolysis and photocatalysis are well-known processes for hydrogen production and their efficiency relies on electrocatalysts, which are generally noble metals. The usage of noble metals as catalysts makes these processes costly and their scarcity is also a limiting factor. Metal nitrides and their porous counterparts have drawn considerable attention from researchers due to their good promise for hydrogen production. Their properties such as active metal centres, nitrogen functionalities, and porous features such as surface area, pore-volume, and tunable pore size could play an important role in electrochemical and photocatalytic hydrogen production. This review focuses on the recent developments in metal nitrides from their synthesis methods point of view. Much attention is given to the emergence of new synthesis techniques, methods, and processes of synthesizing the metal nitride nanostructures. The applications of electrochemical and photocatalytic hydrogen production are summarized. Overall, this review will provide useful information to researchers working in the field of metal nitrides and their application for hydrogen production.

The emergence of nanoporous materials in lung cancer therapy.

Lung cancer is one of the most common cancers, affecting more than 2.1 million people across the globe every year. A very high occurrence and mortality rate of lung cancer have prompted active research in this area with both conventional and novel forms of therapies including the use of nanomaterials based drug delivery agents. Specifically, the unique physico-chemical and biological properties of porous nanomaterials have gained significant momentum as drug delivery agents for delivering a combination of drugs or merging diagnosis with targeted therapy for cancer treatment. This review focuses on the emergence of nano-porous materials for drug delivery in lung cancer. The review analyses the currently used nanoporous materials, including inorganic, organic and hybrid porous materials for delivering drugs for various types of therapies, including chemo, radio and phototherapy. It also analyses the selected research on stimuli-responsive nanoporous materials for drug delivery in lung cancer before summarizing the various findings and projecting the future of emerging trends. This review provides a strong foundation for the current status of the research on nanoporous materials, their limitations and the potential for improving their design to overcome the unique challenges of delivering drugs for the treatment of lung cancer.

Redox Active Cerium Oxide Nanoparticles: Current Status and Burning Issues.

Research on cerium oxide nanoparticles (nanoceria) has captivated the scientific community due to their unique physical and chemical properties, such as redox activity and oxygen buffering capacity, which made them available for many technical applications, including biomedical applications. The redox mimetic antioxidant properties of nanoceria have been effective in the treatment of many diseases caused by reactive oxygen species (ROS) and reactive nitrogen species. The mechanism of ROS scavenging activity of nanoceria is still elusive, and its redox activity is controversial due to mixed reports in the literature showing pro-oxidant and antioxidant activity. In light of its current research interest, it is critical to understand the behavior of nanoceria in the biological environment and provide answers to some of the critical and open issues. This review critically analyzes the status of research on the application of nanoceria to treat diseases caused by ROS. It reviews the proposed mechanism of action and shows the effect of surface coatings on its redox activity. It also discusses some of the crucial issues in deciphering the mechanism and redox activity of nanoceria and suggests areas of future research.

Silica-Based Nanoparticles as Drug Delivery Vehicles for Prostate Cancer Treatment.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers and is the fifth common cause of cancer-related mortality in men. Current methods for PCa treatment are insufficient owing to the challenges related to the non-specificity, instability and side effects caused by the drugs and therapy agents. These drawbacks can be mitigated by the design of a suitable drug delivery system that can ensure targeted delivery and minimise side effects. Silica based nanoparticles (SBNPs) have emerged as one of the most versatile materials for drug delivery due to their tunable porosities, high surface area and tremendous capacity to load various sizes and chemistry of drugs. This review gives a brief overview of the diagnosis and current treatment strategies for PCa outlining their existing challenges. It critically analyzes the design, development and application of pure, modified and hybrid SBNPs based drug delivery systems in the treatment of PCa, their advantages and limitations.

Emerging trends in porous materials for CO2 capture and conversion.

The presence of an excessive concentration of CO2 in the atmosphere needs to be curbed with suitable measures including the reduction of CO2 emissions at stationary point sources such as power plants through carbon capture technologies and subsequent conversion of the captured CO2 into non-polluting clean fuels/chemicals using photo and/or electrocatalytic pathways. Porous materials have attracted much attention for carbon capture and in the recent past; they have witnessed significant advancements in their design and implementation for CO2 capture and conversion. In this context, the emerging trends in major porous adsorbents such as MOFs, zeolites, POPs, porous carbons, and mesoporous materials for CO2 capture and conversion are discussed. Their surface texture and chemistry, and the influence of various other features on their efficiency, selectivity, and recyclability for CO2 capture and conversion are explained and compared thoroughly. The scientific and technical advances on the material structure versus CO2 capture and conversion provide deep insights into designing effective porous materials. The review concludes with a summary, which compiles the key challenges in the field, current trends and critical challenges in the development of porous materials, and future research directions combined with possible solutions for realising the deployment of porous materials in CO2 capture and conversion.

Microporous Carbon Nitride (C3 N5.4 ) with Tetrazine based Molecular Structure for Efficient Adsorption of CO2 and Water.

Mesoporous carbon nitrides with C3 N5 and C3 N6 stoichiometries created a new momentum in the field of organic metal-free semiconductors owing to their unique band structures and high basicity. Here, we report on the preparation of a novel graphitic microporous carbon nitride with a tetrazine based chemical structure and the composition of C3 N5.4 using ultra-stable Y zeolite as the template and aminoguanidine hydrochloride, a high nitrogen-containing molecule, as the CN precursor. Spectroscopic characterization and density functional theory calculations reveal that the prepared material exhibits a new molecular structure, which comprises two tetrazines and one triazine rings in the unit cell and is thermodynamically stable. The resultant carbon nitride shows an outstanding surface area of 130.4 m2 g-1 and demonstrates excellent CO2 adsorption per unit surface area of 47.54 µmol m-2 , which is due to the existence of abundant free NH2 groups, basic sites and microporosity. The material also exhibits highly selective sensing over water molecules (151.1 mmol g-1 ) and aliphatic hydrocarbons due to its unique microporous structure with a high amount of hydrophilic nitrogen moieties and recognizing ability towards small molecules.

An unexpected phase transformation of ceria nanoparticles in aqueous media.

Cerium oxide Nanoparticles (CNPs) are of significant interest to the scientific community due to their wide spread applications in a variety of fields. It is proposed that size dependent variations in the extent of Ce3+ and Ce4+ oxidation states of cerium in CNPs determines the performance of CNPs in application environments. To obtain greater molecular and structural understanding of chemical state transformations previously reported for ceria ≈ 3 nm nanoparticles (CNPs) in response to changing ambient conditions, microXRD and Raman measurements were carried out for various solution conditions. The particles were observed to undergo a reversible transformation from a defective ceria structure to a non-ceria amorphous oxy-hydroxide/peroxide phase in response to the addition of 30% hydrogen peroxide. For CNPs made up of ~8 nm crystallites, a partial transformation was observed and no transformation was observed for CNPs made up of ~ 40 nm crystallites. This observation of differences in size dependent transition behavior may help explain the benefits of using smaller CNPs in applications requiring regenerative behavior.

Redox-Sensitive Cerium Oxide Nanoparticles Protect Human Keratinocytes from Oxidative Stress Induced by Glutathione Depletion.

Cerium oxide nanoparticles (CeNPs) have gathered much attention in the biomedical field due to its unique antioxidant property. It can protect cells and tissues from oxidative stress induced damage due to its autoregenerative redox cycle. Our study explores the antioxidant and antigenotoxic behavior of PEGylated CeNPs toward oxidative insult produced by buthionine sulfoximine (BSO) in human keratinocytes (HaCaT cells). BSO inhibits the γ-glutamylcysteinesynthetase (γ-GCS) enzyme and thus acts as a glutathione (GSH) depleting agent to modulate the cellular redox potential. GSH is a natural ROS scavenger present in the mammalian cells, and its depletion causes generation of reactive oxygen species (ROS). In this study, we challenged HaCaT cells (keratinocytes) with BSO to alter the redox potential within the cell and monitored toxicity, ROS generation, and nuclear fragmentation. We also followed changes in expressions of related proteins and genes. We found that PEGylated CeNPs can protect HaCaT cells from BSO-induced oxidative damage. BSO-exposed cells, preincubated with PEGylated CeNPs, showed better cell survival and significant decrease in the intracellular levels of ROS. We also observed decrease in lactate dehydrogenase (LDH) release and nuclear fragmentation in CeNP-treated cells that were challenged with BSO as compared to treatment with BSO alone. Exposure of HaCaT cells with BSO leads to altered expression of antioxidant genes and proteins, i.e., thioredoxin reductase (TrxR) and peroxiredoxin 6 (Prx6) whereas, in our study, pretreatment of PEGylated CeNPs reduces the need for induction of genes that produce enzymes involved in the defense against oxidative stress. Since, growing evidence argued the involvement of ROS in mediating death of mammalian cells in several ailments, our finding reinforces the use of PEGylated CeNPs as a potent pharmacological agent under the lower cellular GSH/GSSG ratios for the treatment of diseases mediated by free radicals.

Investigation of trimethylacetic acid adsorption on stoichiometric and oxygen-deficient CeO2(111) surfaces.

We studied the interactions between the carboxylate anchoring group from trimethylacetic acid (TMAA) and CeO2(111) surfaces as a function of oxygen stoichiometry using in situ X-ray photoelectron spectroscopy (XPS). The stoichiometric CeO2(111) surface was obtained by annealing the thin film under 2.0 × 10(-5) Torr of oxygen at ∼550 °C for 30 min. In order to reduce the CeO2(111) surface, the thin film was annealed under ∼5.0 × 10(-10) Torr vacuum conditions at 550 °C, 650 °C, 750 °C and 850 °C for 30 min to progressively increase the oxygen defect concentration on the surface. The saturated TMAA coverage on the CeO2(111) surface determined from XPS elemental composition is found to increase with increasing oxygen defect concentration. This is attributed to the increase of under-coordinated cerium sites on the surface with the increase in the oxygen defect concentrations. XPS results were in agreement with periodic density functional theory (DFT) calculations and indicate a stronger binding between the carboxylate group from TMAA and the oxygen deficient CeO2-δ(111) surface through dissociative adsorption.

Aqueous medium induced optical transitions in cerium oxide nanoparticles.

Experimental and theoretical investigations were performed to investigate the effect of water on optical properties of nanoceria as a function of Ce(3+) concentration. Theoretical studies based on density functional plane-wave calculations reveal that the indirect optical transitions in bare ceria nanoparticles are red-shifted with an increase in the concentration of Ce(3+). However, ceria nanoparticles model with adsorbed water molecules show a blue shift in the indirect optical spectra under identical conditions. Direct optical transitions are almost independent of Ce(3+) concentration but show a pronounced blue shift in the aqueous environment relative to the bare nanoparticles. The theoretical study is consistent with our experimental observation in difference of shift behaviour in bare and aqueous suspended ceria nanoparticles. This change from red- to blue-shift in indirect optical transitions is associated with the polarization effect of water molecules on f-electron states.

Bio-distribution and in vivo antioxidant effects of cerium oxide nanoparticles in mice.

Cerium oxide nanoparticles have oxygen defects in their lattice structure that enables them to act as a regenerative free radical scavenger in a physiological environment. We performed a comprehensive in vivo analysis of the biological distribution and antioxidant capabilities of nanoceria administered to mice perorally (PO), intravenously (IV), or intraperitoneally (IP) by dosing animals weekly for 2 or 5 weeks with 0.5 mg kg(-1) nanoceria. Next, we examined if nanoceria administration would decrease ROS production in mice treated with carbon tetrachloride (CCl(4)). Our results showed that the most extensive and cumulative nano-deposition was via IV and IP administered while PO administration showed mice excreted greater than 95% of their nanoceria within 24 h. Organ deposition for IV and IP mice was greatest in the spleen followed by the liver, lungs, and kidneys. Elimination for all administration routes was through feces. Nanoceria administration showed no overt toxicity, however, WBC counts were elevated with IV and IP administration. Our in vivo studies show that nanoceria administration to mice with induced liver toxicity (by CCl(4)) showed similar findings to mice treated with N-acetyl cystine (NAC), a common therapeutic to reduce oxidative stress. Taken together, our studies show that nanoceria remains deposited in tissues and may decrease ROS, thereby suggesting that cerium oxide nanoparticles may be a useful antioxidant treatment for oxidative stress.

Surface characterization of nanomaterials and nanoparticles: Important needs and challenging opportunities.

This review examines characterization challenges inherently associated with understanding nanomaterials and the roles surface and interface characterization methods can play in meeting some of the challenges. In parts of the research community, there is growing recognition that studies and published reports on the properties and behaviors of nanomaterials often have reported inadequate or incomplete characterization. As a consequence, the true value of the data in these reports is, at best, uncertain. With the increasing importance of nanomaterials in fundamental research and technological applications, it is desirable that researchers from the wide variety of disciplines involved recognize the nature of these often unexpected challenges associated with reproducible synthesis and characterization of nanomaterials, including the difficulties of maintaining desired materials properties during handling and processing due to their dynamic nature. It is equally valuable for researchers to understand how characterization approaches (surface and otherwise) can help to minimize synthesis surprises and to determine how (and how quickly) materials and properties change in different environments. Appropriate application of traditional surface sensitive analysis methods (including x-ray photoelectron and Auger electron spectroscopies, scanning probe microscopy, and secondary ion mass spectroscopy) can provide information that helps address several of the analysis needs. In many circumstances, extensions of traditional data analysis can provide considerably more information than normally obtained from the data collected. Less common or evolving methods with surface selectivity (e.g., some variations of nuclear magnetic resonance, sum frequency generation, and low and medium energy ion scattering) can provide information about surfaces or interfaces in working environments (operando or in situ) or information not provided by more traditional methods. Although these methods may require instrumentation or expertise not generally available, they can be particularly useful in addressing specific questions, and examples of their use in nanomaterial research are presented.

Recent Advances in Carbon-Based Electrodes for Energy Storage and Conversion.

Carbon-based nanomaterials, including graphene, fullerenes, and carbon nanotubes, are attracting significant attention as promising materials for next-generation energy storage and conversion applications. They possess unique physicochemical properties, such as structural stability and flexibility, high porosity, and tunable physicochemical features, which render them well suited in these hot research fields. Technological advances at atomic and electronic levels are crucial for developing more efficient and durable devices. This comprehensive review provides a state-of-the-art overview of these advanced carbon-based nanomaterials for various energy storage and conversion applications, focusing on supercapacitors, lithium as well as sodium-ion batteries, and hydrogen evolution reactions. Particular emphasis is placed on the strategies employed to enhance performance through nonmetallic elemental doping of N, B, S, and P in either individual doping or codoping, as well as structural modifications such as the creation of defect sites, edge functionalization, and inter-layer distance manipulation, aiming to provide the general guidelines for designing these devices by the above approaches to achieve optimal performance. Furthermore, this review delves into the challenges and future prospects for the advancement of carbon-based electrodes in energy storage and conversion.