The Potential of Epigallocatechin Gallate in Targeting Cancer Stem Cells: A Comprehensive Review.

The dreadful scenario of cancer prevails due to the presence of cancer stem cells (CSCs), which contribute to tumor growth, metastasis, invasion, resistance to chemo- and radiotherapy, and recurrence. CSCs are a small subpopulation of cells within the tumor that are characterized by self-renewal capability and have the potential to manifest heterogeneous lineages of cancer cells that constitute the tumor. The major bioactive green tea polyphenol (-)-epigallocatechin gallate (EGCG) has been fruitful in downgrading cancer stemness signaling and CSC biomarkers in cancer progression. EGCG has been evidenced to maneuver extrinsic and intrinsic apoptotic pathways in order to decrease the viability of CSCs. Cancer stemness is intricately related to epithelial-mesenchymal transition (EMT), metastasis and therapy resistance, and EGCG has been evidenced to regress all these CSC-related effects. By inhibiting CSC characteristics EGCG has also been evidenced to sensitize the tumor cells to radiotherapy and chemotherapy. However, the use of EGCG in in vitro and in vivo cancer models raises concern about its bioavailability, stability and efficacy against spheroids raised from parental cells. Therefore, novel nano formulations of EGCG and adjuvant therapy of EGCG with other phytochemicals or drugs or small molecules may have a better prospect in targeting CSCs. However, extensive clinical research is still awaited to elucidate a full proof impact of EGCG in cancer therapy.

Delivery platforms for broadly neutralizing antibodies.

PURPOSE OF REVIEW: Passive administration of broadly neutralizing antibodies (bNAbs) is being evaluated as a therapeutic approach to prevent or treat HIV infections. However, a number of challenges face the widespread implementation of passive transfer for HIV. To reduce the need of recurrent administrations of bNAbs, gene-based delivery approaches have been developed which overcome the limitations of passive transfer. RECENT FINDINGS: The use of DNA and mRNA for the delivery of bNAbs has made significant progress. DNA-encoded monoclonal antibodies (DMAbs) have shown great promise in animal models of disease and the underlying DNA-based technology is now being tested in vaccine trials for a variety of indications. The COVID-19 pandemic greatly accelerated the development of mRNA-based technology to induce protective immunity. These advances are now being successfully applied to the delivery of monoclonal antibodies using mRNA in animal models. Delivery of bNAbs using viral vectors, primarily adeno-associated virus (AAV), has shown great promise in preclinical animal models and more recently in human studies. Most recently, advances in genome editing techniques have led to engineering of monoclonal antibody expression from B cells. These efforts aim to turn B cells into a source of evolving antibodies that can improve through repeated exposure to the respective antigen. SUMMARY: The use of these different platforms for antibody delivery has been demonstrated across a wide range of animal models and disease indications, including HIV. Although each approach has unique strengths and weaknesses, additional advances in efficiency of gene delivery and reduced immunogenicity will be necessary to drive widespread implementation of these technologies. Considering the mounting clinical evidence of the potential of bNAbs for HIV treatment and prevention, overcoming the remaining technical challenges for gene-based bNAb delivery represents a relatively straightforward path towards practical interventions against HIV infection.

Efficient Charge-Transfer Studies for Selective Detection of Bilirubin Biomolecules Using CsPbBr3 as the Fluorescent Probe.

Bright luminescence hybrid halide perovskite nanocrystals (PNCs) as a novel fluorophore class have not been broadly explored in biological sensing. Herein, we synthesized highly fluorescent CsPbBr3 PNCs through the LARP method using oleic acid and oleyl amine as capping ligands. Morphological and optical properties of as-synthesized PNCs were studied using transmission electron microscopy, X-ray diffraction, UV-vis, and emission spectroscopic analysis. Oleic acid- and oleyl amine-capped PNCs are employed for sensitive and selective detection of bilirubin (BR). A panel of characterizations (time-correlated single-photon count spectroscopy and photoluminescence (PL)) was carried out to investigate the detailed sensing study of PNCs-BR composite for quenching the PL emission of CsPbBr3 with BR. It has been noticed that the synthesized nanoparticles are highly capable of detecting BR and thus act as a biological material sensor.

Air stable highly luminescent 2D tin halide perovskite nanocrystals as photodetectors.

Hybrid and inorganic perovskite nanocrystals are a hot topic in materials chemistry due to their versatile optoelectronic properties. Herein, we report highly luminescent water stable lead-free orange emissive (OleylAm)2SnBr4 (OleylAm = oleylammonium cation) 2D tin halide perovskite nanocrystals in humid conditions in a solution-based process. The photoresponse study performed with the synthesized nanocrystals exhibits a responsivity of 4.9 mA W-1 at a 5 V operating voltage.

A Room-Temperature Spin-Valve with van der Waals Ferromagnet Fe5 GeTe2 /Graphene Heterostructure.

The discovery of van der Waals (vdW) magnets opened a new paradigm for condensed matter physics and spintronic technologies. However, the operations of active spintronic devices with vdW ferromagnets are limited to cryogenic temperatures, inhibiting their broader practical applications. Here, the robust room-temperature operation of lateral spin-valve devices using the vdW itinerant ferromagnet Fe5 GeTe2 in heterostructures with graphene is demonstrated. The room-temperature spintronic properties of Fe5 GeTe2 are measured at the interface with graphene with a negative spin polarization. Lateral spin-valve and spin-precession measurements provide unique insights by probing the Fe5 GeTe2 /graphene interface spintronic properties via spin-dynamics measurements, revealing multidirectional spin polarization. Density functional theory calculations in conjunction with Monte Carlo simulations reveal significantly canted Fe magnetic moments in Fe5 GeTe2 along with the presence of negative spin polarization at the Fe5 GeTe2 /graphene interface. These findings open opportunities for vdW interface design and applications of vdW-magnet-based spintronic devices at ambient temperatures.

Gene Alterations Induced by Glutamine (Q) Encoding CAG Repeats Associated with Neurodegeneration.

Several studies have been reported linking the role of polyglutamine (polyQ) disease-associated proteins with altered gene regulation induced by an unstable trinucleotide (CAG) repeat. Owing to their dynamic nature of expansion, these DNA repeats form secondary structures interfering with the normal cellular mechanisms like replication and transcription and, thereby, have become the underlying cause of numerous neurodegenerative disorders involving mental retardation and/or muscular or neuronal degeneration. Despite the widespread expression of the disease-causing protein, specific subsets of neurons are susceptible to specific patterns of inheritance and clinical symptoms. Although this cell-type selectivity is still elusive and less understood, it has been found that aberrant transcriptional regulation is one of the primary causes of polyQ diseases where the functions of histone-modifying complexes are disrupted. Besides, epigenetic modifications play a critical role in the pathogenesis of these diseases. In this chapter, we will be delving into how these polyQ repeats induce the self-assembly and aggregation of altered carrier proteins based on gene alterations, causing neuronal toxicity and cellular deaths. Besides, genomic instability in CAG repeats due to altered chromatin-related enzymes will be highlighted, along with epigenetic changes present in many polyQ disorders. Understanding the underlying molecular mechanisms in the root cause of these disorders will culminate in identifying therapeutic approaches for the treatment of these neurodegenerative disorders.

Influence of differential arsenic exposure on cellular redox homeostasis of exposed rural women of West Bengal.

The metalloid arsenic (As) induces oxidative stress is a well-known fact. However, the extent of variation of oxidative stress according to different exposure levels of As in groundwater and the mechanism responsible for As mediated oxidative stress is yet to be elucidated in a human population of West Bengal. In the present study, we have investigated the impact of low level (> 10 ≤ 50 µg/L) and high-level groundwater As (> 50 µg/L) on cellular redox status, DNA damage, and repair mechanisms in chronically exposed rural women of West Bengal. Prediction models of ordinary least square regression of nail As, forced vital capacity (FVC) %, and that of forced expiratory volume during the first one second (FEV1) % deciphered that accumulation of As in nails may predict hemoglobin deficiency. Moreover, consumption of As-laced water tends to decrease FEV1% and FVC%. A strong positive correlation was observed between water and nail As level and reactive oxygen species (ROS) generation. ROS, perturbed nuclear factor erythroid 2-related factor 2(Nrf2)/ Kelch-like ECH-associated protein 1 (Keap1) redox regulation, compromised antioxidant defense machinery-superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione transferase (GST), induced DNA damage, and suppressed DNA repair proteins-poly ADP ribose polymerase1(PARP1)/ X-ray repair cross-complementing protein 1(XRCC1)/ 8-oxoguanine glycosylase (OGG1) in a dose-dependent manner. All the low and high As areas had very high cancer risk values for the exposed population. It has been predicted that if the As level in the drinking water of a 40-year adult increases by 2 ug/L, the likelihood of the cancer risk will increase by 10%, keeping the body weight and amount of water intake constant. Thus, long-term exposure to either low or high As is seriously affecting the lives of asymptomatic women who are vulnerable to developing carcinogenic changes after a period of latency.

Virus-Like Particles of SARS-CoV-2 as Virus Surrogates: Morphology, Immunogenicity, and Internalization in Neuronal Cells.

The engineering of virus-like particles (VLPs) is a viable strategy for the development of vaccines and for the identification of therapeutic targets without using live viruses. Here, we report the generation and characterization of quadruple-antigen SARS-CoV-2 VLPs. VLPs were generated by transient transfection of two expression cassettes in adherent HEK293T cells─one cassette containing Mpro for processing of three structural proteins (M, E, and N), and the second cassette expressing the Spike protein. Further characterization revealed that the VLPs retain close morphological and antigenic similarity with the native virus and also bind strongly to the SARS-CoV-2 receptor hACE-2 in an in vitro binding assay. Interestingly, the VLPs were found to internalize into U87-MG cells through cholesterol-rich domains in a dynamin-dependent process. Finally, our results showed that mice immunized with VLPs induce robust humoral and cellular immune responses mediated by enhanced levels of IL-4, IL-17, and IFNγ. Taken together, our results demonstrate that VLPs mimic the native virus and induce a strong immune response, indicating the possible use of these particles as an alternative vaccine candidate against SARS-CoV-2. VLPs can also be effective in mapping the initial stages of virus entry and screening inhibitors.

Flexion of Nrf2 by tea phytochemicals: A review on the chemopreventive and chemotherapeutic implications.

Nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2), the redox-sensitive transcription factor, plays a key role in stress-defense and detoxification. Nrf2 is tightly controlled by its negative regulator cum sensor Kelch-[ECH]-associated protein 1 (Keap1). Nrf2 is well known for its dual nature owing to its cancer preventive and cancer promoting abilities. Modulation of this biphasic nature of Nrf2 signaling by phytochemicals may be a potential cancer preventive and anticancer therapeutic strategy. Phytocompounds may either act as Nrf2-activator or Nrf2-inhibitor depending on their differential concentration and varied cellular environment. Tea is not just the most popular global beverage with innumerable health-benefits but has well-established chemopreventive and chemotherapeutic effects. Various types of tea infusions contain a wide range of bioactive compounds, such as polyphenolic catechins and flavonols, which are endowed with potent antioxidant properties. Despite of their rapid biotransformation and poor bioavailability, regular tea consumption is risk-reductive for several cancer forms. Tea catechins show their dual Nrf2-modulatory effect by directly acting on Nrf2-Keap1 or their upstream regulators and downstream effectors in a highly case-specific manner. In this review, we have tried to present a comprehensive evaluation of the Nrf2-mediated chemopreventive and chemotherapeutic applications of tea in various preclinical cancer models, the Nrf2-modulatory mechanisms, and the limitations which need to be addressed in future research.

Aromatic Amino Acid-Mediated Perovskite Nanocrystals: Fluorescence Tuning and Morphological Evolution.

Lead halide perovskites with high fluorescent and tunable morphology appeared at the forefront of materials chemistry because of their corresponding impressive optoelectronic properties. The current advancement of metal halide perovskites put forward the functional and bidentate ligand to expand their utilization in modified ligand chemistry. We successfully introduced nontoxic aromatic amino acid as a capping ligand to synthesize the perovskite nanocrystals (PNCs). The implementation of aromatic amino acid for the construction of CsPbX3 nanocrystals (NCs) provides the synergetic service of the carboxylic and amine groups with the phenyl residue, which prompts the formation of NCs with high fluorescence intensity. The experimental results demonstrate the emissive property of PNCs in a whole visible region with long-term stability. Additionally, the morphology of the NCs has been tuned. We performed several characterization techniques to investigate the nature of the NCs in the solid and solution phases.

Google earth engine based computational system for the earth and environment monitoring applications during the COVID-19 pandemic using thresholding technique on SAR datasets.

Observing the earth and environmental conditions during the COVID-19 pandemic lockdown along with travel restrictions headed to worse circumstance. These scenarios amplified the hurdles of flood management. In order to resolves these issues, an efficient and resilient geospatial framework with unconventional systems is also required for the generation of instantaneous results. Hence to avoid these deficiencies, the google earth engine based computational system integrated with analytical tools for large-scale data handling is introduced for the earth and environmental monitoring applications. The present study proposes a working model for geospatial data processing to understand socio-demographic implications with a web-based analytical interface. The research introduces a histogram-based thresholding approach for real-time surface water mapping along with precise data processing and analysis for automated monitoring. The study integrates geospatial datasets to a enhanced data processing methods in a web-based platform to deliver the required results for extensive planning and decision making. Furthermore, a similar type of work can be undertaken for other disaster management applications.

Unusual Magnetic Features in Two-Dimensional Fe5GeTe2 Induced by Structural Reconstructions.

Recent experiments on Fe5GeTe2 suggested the presence of a symmetry breaking of its conventional crystal structure. Here, using density functional theory calculations, we elucidate that the stabilization of the (√3 × âˆš3)R30° supercell structure is caused by the swapping of Fe atoms occurring in the monolayer limit. The swapping to the vicinity of Te atoms is facilitated by the spontaneous occurrence of Fe vacancy and its low diffusion barrier. Our calculated magnetic exchange parameters show the simultaneous presence of ferromagnetic and antiferromagnetic exchange among a particular type of Fe atom. The Fe sublattice projected magnetization obtained from Monte Carlo simulations clearly demonstrates an exotic temperature-dependent behavior of this Fe type along with a large canting angle at T = 0 K, indicating the presence of a complex noncollinear magnetic order. We propose that the low-temperature crystal structure results from the swapping between two sublattices of Fe, giving rise to peculiar magnetization obtained in experiments.

Bioengineering of Extracellular Vesicles: Exosome-Based Next-Generation Therapeutic Strategy in Cancer.

Extracellular nano vesicles and exosomes hold compelling evidence in intercellular communication. Exosomal intracellular signal transduction is mediated by the transfer of cargo proteins, lipids, micro (mi)RNAs, long noncoding (lnc)RNAs, small interfering (si)RNAs, DNA, and other functional molecules that play a pivotal role in regulating tumor growth and metastasis. However, emerging research trends indicate that exosomes may be used as a promising tool in anticancer treatment. This review features a majority of the bioengineering applications of fabricated exosomal cargoes. It also encompasses how the manipulation and delivery of specific cargoes-noncoding RNAs (ncRNAs), recombinant proteins, immune-modulators, chemotherapeutic drugs, and other small molecules-may serve as a precise therapeutic approach in cancer management.

Overcoming the asymmetry of the electron and hole doping for magnetic transitions in bilayer CrI3.

Electrical control of magnetism has great potential for low-power spintronics applications and the newly discovered two-dimensional van der Waals magnetic materials are promising systems for this type of applications. In fact, it has been recently shown experimentally (Jiang et al., Nat. Nanotechnol., 2018, 13, 549-553) that upon electrostatic doping by electrons bilayer CrI3 undergoes an antiferromagnetic-ferromagnetic (AFM-FM) phase transition, even in the absence of magnetic field. Doping by holes, on the other hand, does not induce the same transition in the experiment, which points to an intrinsic asymmetry in the hole and electron doping that limits the control of the transition by doping. We here show, based on first-principles calculations, that the asymmetry originates in the relativistic nature of the valence-band-edge states of the pristine bilayer, which inhibits the magnetic transition upon hole doping. Based on this finding, we propose an approach to overcome the asymmetry and predict the existence of the AFM-FM transition for both hole and electron doping upon moderate uniaxial compression along the soft direction of the bilayer.

A smart viral vector for targeted delivery of hydrophobic drugs.

Targeted delivery of hydrophobic chemotherapeutic drugs to tumor cells remains a fundamental problem in cancer therapy. Effective encapsulation of hydrophobic drugs in nano-vehicles can improve their pharmacokinetics, bioavailability and prevent off-target localization. We have devised a method for easy chemical conjugation and multivalent display of a tumor-homing peptide to virus-like particles of a non-mammalian virus, Flock House Virus (FHV), to engineer it into a smart vehicle for targeted delivery of hydrophobic drugs. This conjugation method provides dual functionalization to the VLPs, first, a 2 kDa PEG spacer arm shields VLPs from immune reactivity, and second, attachment of the tumor homing peptide tLyP-1 chauffeurs the encapsulated hydrophobic drugs to target cells. The fortuitous affinity of the FHV capsid towards hydrophobic molecules, and dependence on Ca2+ for maintaining a stable capsid shell, were utilized for incorporation of hydrophobic drugs-doxorubicin and ellipticine-in tLyP-1 conjugated VLPs. The drug release profile from the VLP was observed to be gradual, and strictly endosomal pH dependent. We propose that this accessible platform empowers surface functionalization of VLP with numerous ligands containing terminal cysteines, for generating competent delivery vehicles, antigenic display and other biomedical applications.

Investigating the property of water driven lead-free stable inorganic halide double perovskites.

Lead free halide double perovskite materials, A2BB́X6 (where A, B and B́ are cations and X is a halide anion) have achieved considerable attention in the field of optoelectronic devices due to their high thermal along with the moisture stability and less toxicity as lead halide perovskites suffer from the stability and toxicity issues which inhibit them to be commercialized. Therefore, synthesis of low cost and stable perovskite materials are the main focus of perovskite family nowadays. Herein, we have reported lead free Cs2AgBiCl6 and Cs2AgBiBr6 double perovskite microcrystals in both organic and a mixture of the aqueous-organic medium. Our studies are not only eradicating the toxicity of lead but also explored towards the stability of perovskite materials in the aqueous medium. Morphology is investigated using SEM and TEM imaging along with the enhancement in emission peak by increasing the content of water.

Unprecedented formation of reverse micellar vesicles from psuedopeptidic bottlebrush polymers.

Spherical assemblies named "reverse micellar vesicles" from self-assembling psuedopeptidic bottlebrush polymers are reported. These assemblies exhibited the combined features of both micelles and vesicles viz. molecular arrangement of classical micelles and dimensions similar to that of classical vesicles. Comprehensive ultramicroscopic and spectroscopic analyses were performed to delineate the hierarchical mechanism of their formation.

Prostate cancer and sarcoma: Challenges of synchronous malignancies.

Synchronous primary malignancies are a rare finding which can be difficult to diagnose. We present the case of a 57-year-old patient with a high prostate specific antigen who was found to have prostate cancer on subsequent magnetic resonance imaging. A skeletal metastasis was also identified at the time, although no osteoblastic activity or sclerosis was identified on skeletal scintigraphy or computed tomography, respectively. The patient was started on hormonal therapy and follow-up imaging revealed the prostate cancer to have reduced in volume. Despite this, the skeletal metastasis appeared unchanged on magnetic resonance imaging and an F18-choline positron emission tomography study was negative. A computed tomography guided bone biopsy was organized and this demonstrated metastatic leiomyosarcoma. As a result, an F18-fluorodeoxyglucose positron emission tomography study was performed to find the primary lesion which demonstrated a large malignant tumor within the calf. Subsequently, the patient was referred to a tertiary sarcoma unit. This case highlights the challenges involved in diagnosing and managing synchronous malignancies.

Support work function as a descriptor and predictor for the charge and morphology of deposited Au nanoparticles.

We show, using density functional theory calculations, that the charge, magnetic moment, and morphology of deposited Au nanoclusters can be tuned widely by doping the oxide support with aliovalent cations and anions. As model systems, we have considered Aun (n = 1, 2, or 20) deposited on doped MgO and MgO/Mo supports. The supports have been substitutionally doped with varying concentrations θ of F, Al, N, Na, or Li. At θ = 2.78%, by varying the dopant species, we are able to tune the charge of the Au monomer between -0.84e and +0.21e, the Au dimer between -0.87e and -0.16e, and, most interestingly, Au20 between -3.97e and +0.49e. These ranges can be further extended by varying θ. These changes in charge are correlated with changes in adsorption and/or cluster geometry and magnetic moment. We find that the work function Φ of the bare support is a good predictor and descriptor of both the geometry and charge of the deposited Au cluster; it can, therefore, be used to quickly estimate which dopant species and concentration can result in a desired cluster morphology and charge state. This is of interest as these parameters are known to significantly impact cluster reactivity, with positively or negatively charged clusters being preferred as catalysts for different chemical reactions. It is particularly noteworthy that the Na-doped and Li-doped supports succeed in making Au20 positively charged, given the high electronegativity of Au.