γc cytokine-aided crosstalk between dendritic cells and natural killer cells together with doxorubicin induces a healer response in experimental lymphoma by downregulating FOXP3 and programmed cell death protein 1.

BACKGROUND AIMS: The stimulatory natural killer-dendritic cell axis in the tumor microenvironment could play a critical role in stimulating cytotoxic T cells and driving immune responses against cancer. METHODS: We established a novel treatment protocol by adroitly combining chemotherapy with doxorubicin and immunotherapy with dendritic cells and natural killer cells against a highly aggressive and malignant lymphoma called Dalton's lymphoma. RESULTS: Our data suggest that binary application of adoptive cell therapy and chemotherapy nearly cures (95%) early-stage experimental lymphoma. In the case of mid-stage cancer, the success rate was significantly lower but still impressive (75%). Our results demonstrated that the application of combination therapy in early-stage cancer significantly reduced the tumor volume and extended the lifespan of the experimental animal in addition to reinvigorating the immune system, including restoring the effector functions of dendritic cells and natural killer cells. The novel protocol limits the metastasis of tumor cells in vascularized organs and rearms the adaptive immune response mediated by dendritic cells and CD4+ and CD8+ T cells. CONCLUSIONS: Combination therapy in the early stage alters the cytokine profile, increases interferon-γ and tumor necrosis factor-α in the serum of treated animals and downregulates programmed cell death protein 1 expression in CD8+ T cells. Thus, cooperative and cognitive interactions between dendritic cells and natural killer cells in addition to therapy with doxorubicin promote the immune response and tumoricidal activities against lymphoma.

Obstructed Surface States as the Descriptor for Predicting Catalytic Active Sites in Inorganic Crystalline Materials.

The discovery of new catalysts that are efficient and sustainable is a major research endeavor for many industrial chemical processes. This requires an understanding and determination of the catalytic origins, which remains a challenge. Here, a novel method to identify the position of active sites based on searching for crystalline symmetry-protected obstructed atomic insulators (OAIs) that have metallic surface states is described. The obstructed Wannier charge centers (OWCCs) in OAIs are pinned by symmetries at some empty Wyckoff positions so that surfaces that accommodate these sites are guaranteed to have metallic obstructed surface states (OSSs). It is proposed and confirmed that the OSSs are the catalytic activity origins for crystalline materials. The theory on 2H-MoTe2 , 1T'-MoTe2 , and NiPS3 bulk single crystals is verified, whose active sites are consistent with the calculations. Most importantly, several high-efficiency catalysts are successfully identified just by considering the number of OWCCs and the symmetry. Using the real-space-invariant theory applied to a database of 34 013 topologically trivial insulators, 1788 unique OAIs are identified, of which 465 are potential high-performance catalysts. The new methodology will facilitate and accelerate the discovery of new catalysts for a wide range of heterogeneous redox reactions.

Effect of magnetic field on the hydrogen evolution activity using non-magnetic Weyl semimetal catalysts.

An external switch to control the kinetics of the reaction by manipulating the participating electrons could be interesting as it can alter the rate of the reaction without affecting the reaction pathway. The magnetic field, like a switch, is non-invasive, tunable, and clean; it can also alter the electrons in a material. We study the effect of an applied magnetic field on the hydrogen evolution activity of the NbP family of Weyl semimetals because of their extremely high mobility and large magnetoresistance at room temperature and good hydrogen evolution properties. We find that by applying a magnetic field of ∼3500 G, the hydrogen evolution activity of NbP increases by up to 95%. The other members of this Weyl semimetal family (viz. TaP, NbAs, and TaAs) also exhibit increased hydrogen evolution activity. Thus, our observations suggest an interplay of electronic property, magnetic field, and catalytic activity in this class of compounds, providing evidence of manipulating the catalytic performance of topological materials through the application of a magnetic field.

Studies on interaction potency model based on drug synergy and therapeutic potential of triple stimuli-responsive delivery of doxorubicin and 5-fluoro-2-deoxyuridine against lymphoma using disulfide-bridged cysteine over mesoporous silica nanoparticles.

A triple stimuli-responsive drug delivery platform involving doxorubicin, 5-fluoro-2-deoxy uridine and folic acid was fabricated on mesoporous silica nanoparticles for targeting delivery against a highly aggressive murine lymphoma called Dalton's lymphoma. Fabrication of the unique construct by amalgamating active and passive targeting mechanisms offers a novel hyper-chimeric platform for a stimuli-responsive drug delivery system. The novel construct enables efficient and precise delivery of the precious cargo to the tumor sites. Active targeting by folic acid directs the doxorubicin and 5-fluoro-2-deoxy uridine in the close proximities of the tumor cells, causing efficient killing and significant growth inhibition. Isobologram models, zero interaction potency dose-response surface plots and matrices were generated to evaluate the combination synergism of the two drugs. Therapy with the dual drug-bearing construct in mice with established tumors significantly reduced the tumor load and enhanced the survival of the animals compared with the untreated control. Therapy with the dual delivery system also augmented the innate and adaptive immune defense mechanisms of the treated animals. CD8+ T cells, natural killer cells and the dendritic cells from the treated group following successful therapy with the novel construct showed enhanced cytotoxicity and growth inhibitory capacities against DL tumor cells.

Essential role of TNF-α in gamma c cytokine aided crosstalk between dendritic cells and natural killer cells in experimental murine lymphoma.

Cooperative and cognitive interaction between the dendritic cells and natural killer cells was investigated for demonstrating the anti-tumor activity against an aggressive murine lymphoma, treated with doxorubicin. Crosstalk between the dendritic cells and the natural killer cells significantly reduced the proliferation of Dalton's lymphoma cells in a dose dependent manner. Treatment of Dalton's lymphoma cells with doxorubicin in vitro enhances the effects of crosstalk against the target cells. This crosstalk between the cells was regulated via stimulation with recombinant interleukin-15, and release of TNF-α which is critically important for the tumoricidal effects. Dendritic cells and the natural killer cells crosstalk activate both the cells and upregulate the expression of CD40, CD69 and CD86 on the dendritic cells. These findings provided new insight regarding these interactions and define a mechanism by which cellular immune response promotes tumoricidal activity against lymphoma in therapeutic setting.

Covalently Linked Heterostructures of Phosphorene with MoS2/MoSe2 and Their Remarkable Hydrogen Evolution Reaction Activity.

Hydrogen production by photochemical and electrochemical means is an important area of research related to renewable energy. 2D nanomaterials such as C3N4 and MoS2 have proven to be active for the hydrogen evolution reaction (HER). Phosphorene, a mono-elemental 2D layer of phosphorus, is known to catalyze the HER, but the activity is marginal. The use of phosphorene is also limited by its ambient instability. We have been able to prepare covalently cross-linked nanocomposites of phosphorene with MoS2 as well as MoSe2. The phosphorene-MoS2 nanocomposite shows excellent photochemical HER activity yielding 26.8 mmol h-1 g-1 of H2, while only a negligible amount is produced by the physical mixture of phosphorene and MoS2. The phosphorene-MoS2 composite also displays high electrochemical HER activity with an onset overpotential of 110 mV, close to that of Pt. The enhanced HER activity of the phosphorene-MoS2 nanocomposite can be attributed to the ordered cross-linking of the 2D sheets, increasing the interfacial area as well as the charge-transfer interaction between phosphorene and MoS2 layers. The phosphorene-MoSe2 nanocomposite also exhibits good photochemical HER activity.

Dependence of the Properties of 2D Nanocomposites Generated by Covalent Crosslinking of Nanosheets on the Interlayer Separation: A Combined Experimental and Theoretical Study.

Covalently cross-linked heterostructures of 2D materials are a new class of materials which possess electrochemical and photochemical hydrogen evolution properties. It was of considerable interest to investigate the role of interlayer spacing in the nanocomposites involving MoS2 and graphene sheets and its control over electronic structures and catalytic properties. We have investigated this problem with emphasis on the hydrogen evolution properties of these structures by a combined experimental and theoretical study. We have linked MoS2 based nanocomposites with other 2D materials with varying interlayer spacing by changing the linker and studied their hydrogen evolution properties. The hydrogen evolution activity for these composites decreases with increasing linker length, which we can link to a decrease in magnitude of charge transfer across the layers with increasing interlayer spacing. Factors such as the nature of the sheets, interlayer distance as well as the nature of the linker provide pathways to tune the properties of covalently cross-linked 2D material rendering this new class of materials highly interesting.

Supramolecularly Bonded Layered Heterostructures Exhibiting HER Activity.

van der Waals heterostructures formed by 2D materials have attracted much attention in the last few years. Recently, 2D nanosheets linked by covalent bonds have been found to exhibit novel properties. In the present study we have investigated supramolecular layered heterostructures formed by nanosheets of MoS2 with BC7 N, g-C3 N4 and graphene. These materials have been synthesized via a non-covalent host-guest synthetic design using cucurbit[8]uril (CB[8]) hosts. In addition to offering reversible disassembly, these heterostructures show good visible-light-driven hydrogen evolution reaction (HER) activity as well as reasonable gas adsorption and other properties.

In silico studies and evaluation of antiparasitic role of a novel pyruvate phosphate dikinase inhibitor in Leishmania donovani infected macrophages.

The present work deals with the identification and characterization of a novel inhibitor Z220582104, specific to pyruvate phosphate dikinase, for leishmanicidal activities against free promastigotes and intracellular amastigotes. We have used structure-based drug designing approaches and performed homology modelling, virtual screening and molecular dynamics studies. Primary mouse macrophages and macrophage cell line J774A1 were infected with promastigotes of Leishmania donovani. Both promastigotes and infected macrophages were subjected to treatment with the varying concentrations of Z220582104 or miltefosine for assessment of leishmanicidal activity. The novel inhibitor Z220582104 demonstrated growth inhibitory potential and reduced the viability of the free promastigotes in a concentration- and time-dependent manner. Z220582104 was also effective against the intracellular form of the parasites and reduced the number of amastigotes in macrophages and also lowered the parasite index, compared with the untreated infected macrophages. Although less effective compared with the miltefosine, Z220582104 is well tolerated by the dividing cells and normal human lymphocytes and monocytes with no adverse effects on the growth kinetics or viability. Our in silico and in vitro studies suggested that Leishmania donovani pyruvate phosphate dikinase could be a potential new drug target.

Photochemical and Photoelectrochemical Hydrogen Generation by Splitting Seawater.

Producing hydrogen from water in an efficient manner could significantly reduce consumption of fossil fuels. In this regard the abundant presence of water in oceans offers an important alternative approach for water splitting using seawater. Direct use of seawater for the generation of hydrogen is a difficult and complex process due to the presence of various ions in seawater, which affect the activity of the catalysts and makes the selectivity towards efficient water splitting a challenging task. Herein various ways are reported to efficiently reduce seawater to hydrogen under visible light irradiation by various catalysts already reported by this group. A better performance than pure water was observed in some cases, and in a few cases the opposite was observed, implying that with a proper approach seawater can be efficiently reduced to generate hydrogen.

Mix headache: A valid clinical entity?

BACKGROUND: Chronic daily headache (CDH) patients respond better with a combination of anti-migraine and anti-stress medications, irrespective of clinical diagnosis of chronic migraine (CM) or chronic tension-type headache (CTTH). HYPOTHESIS: "CDH: Mix headache" type is a valid clinical entity. MATERIALS AND METHODS: A total of 70 participants fulfilling the diagnosis of "primary CDH", aged between 15 and 55 years were taken up for the present study. All these patients were subdivided into either CM or CTTH, based on the predominance of symptom profiles in these patients, in confirmation with the International Headache Society guidelines (International Classification of Headache Disorders-2, 2004). Schedules for clinical assessment in neuropsychiatry (SCAN) were applied to these patients to collect information about any mental or behavioral symptoms present at the time of the study. Psychiatric comorbidity was confirmed according to the International Classification of Diseases (ICD)-10. RESULTS: Forty-eight (68.6%) patients could be differentiated into CM and rest 22 (31.4%) patients were given a diagnosis of CTTH. SCAN and ICD-10 diagnosis revealed the presence of comorbid anxiety and depressive illness in 47 (67.2%) patients. Thirty-four of them belonged to CM (MH) group and the rest 13 had CTTH. DISCUSSION: We propose that these 47 (67.2%) patients of CDH form our special category of "CDH - mix headache" subtype. Thus, 14 (20%) patients constitute "CDH - migraine" subtype and rest 9 (12.8%) patients have a diagnosis of "CDH - tension headache" subtype. CONCLUSION: Findings of the present study validate the concept of "mix headache" and explains the clinical observation that chronic daily headache (CDH) patients responds better with a combination of anti-migraine and anti-stress medications.

ATP-Decorated Mesoporous Silica for Biomineralization of Calcium Carbonate and P2 Purinergic Receptor-Mediated Antitumor Activity against Aggressive Lymphoma.

Adenosine triphosphate (ATP) is an important transmitter that mediates various biological effects via purinergic receptors (P2 receptors) in cancer. We investigated the antitumor activity of ATP-decorated and doxorubicin (DOX)-loaded mesoporous silica with biomineralization of calcium carbonate against a highly aggressive and metastatic murine lymphoma called Dalton's lymphoma (DL). Our results suggest that this nanocomposite has unique effects with respect to the morphology and properties of calcium carbonate on the surface of the nanoparticle. DOX in the nanoparticles was prevented from quick release via the interactions of the phosphate group present on ATP and calcium carbonate. This construct is significantly tumoricidal against parental and DOX-resistant DL cells and is thus a promising candidate for applications in drug delivery. The composite nanomaterial has excellent biocompatibility with higher uptake and acts via the participation of the purinergic receptor P2X7. The nanocomposite induces significantly higher apoptosis in tumor cells compared with DOX alone. Treatment of DL-bearing mice with the construct significantly reduces tumor burden, in addition to augmenting the lifespan of tumor-bearing mice as demonstrated by a sustained healthy life of the animals and improved histopathological parameters.

A covalently conjugated MoS2/Fe3O4 magnetic nanocomposite as an efficient & reusable catalyst for H2 production.

Quick and easy recovery without the loss of the photocatalytic activity of the catalysing agent is an effective way to meet the challenges associated with the high cost of hazard-free hydrogen production. A '2D/0D' covalently conjugated nanocomposite of MoS2/Fe3O4 has shown efficient catalyzing ability for five cycles of dye-sensitized H2 evolution.

Pepsin Assisted Doxorubicin Delivery from Mesoporous Silica Nanoparticles Downsizes Solid Tumor Volume and Enhances Therapeutic Efficacy in Experimental Murine Lymphoma.

Pepsin, a digestive enzyme, plays an important role in the metabolism of protein products in the stomach. The pH is regarded as the most pivotal criteria in appraising the pepsin's enzymatic activity. Pepsin is idle at the physiological pH (7.4) but dynamic in the acidic environments of the stomach (pH 2.0-4.0). Inspired by such pH regulatory actions, we have used pepsin as an enhancer, which is attached to silica nanoparticles for the doxorubicin release in the acidic tumor environment. Pepsin enzyme is transitional between the doxorubicin loaded silica nanoparticles and the biotin-avidin cap system, which intercedes the pores. The formed nanoplatform is poised at the physiological pH. However, when switched to low pH simulated conditions, the pepsin become vibrant and cleaves the avidin, rendering the clearance of the path for the diffusion of the drug. This design strategy augmented the drug bioavailability deep inside the solid tumor with enhanced uptake and apoptosis of the tumor cells in experimental lymphoma.

Photochemical Water Splitting by Bismuth Chalcogenide Topological Insulators.

As one of the major areas of interest in catalysis revolves around 2D materials based on molybdenum sulfide, we have examined the catalytic properties of bismuth selenides and tellurides, which are among the first chalcogenides to be proven as topological insulators (TIs). We find significant photochemical H2 evolution activity with these TIs as catalysts. H2 evolution increases drastically in nanosheets of Bi2 Te3 compared to single crystals. First-principles calculations show that due to the topology, surface states participate and promote the hydrogen evolution.

Weyl Semimetals as Hydrogen Evolution Catalysts.

The search for highly efficient and low-cost catalysts is one of the main driving forces in catalytic chemistry. Current strategies for the catalyst design focus on increasing the number and activity of local catalytic sites, such as the edge sites of molybdenum disulfides in the hydrogen evolution reaction (HER). Here, the study proposes and demonstrates a different principle that goes beyond local site optimization by utilizing topological electronic states to spur catalytic activity. For HER, excellent catalysts have been found among the transition-metal monopnictides-NbP, TaP, NbAs, and TaAs-which are recently discovered to be topological Weyl semimetals. Here the study shows that the combination of robust topological surface states and large room temperature carrier mobility, both of which originate from bulk Dirac bands of the Weyl semimetal, is a recipe for high activity HER catalysts. This approach has the potential to go beyond graphene based composite photocatalysts where graphene simply provides a high mobility medium without any active catalytic sites that have been found in these topological materials. Thus, the work provides a guiding principle for the discovery of novel catalysts from the emerging field of topological materials.

Protease-Responsive Targeted Delivery of Doxorubicin from Bilirubin-BSA-Capped Mesoporous Silica Nanoparticles against Colon Cancer.

Bilirubin is regarded as a toxic waste, produced from heme degradation and also acts as a potentially important antioxidant. Bilirubin causes arrest in cell cycle and lead to lesser occurrence of malignancies in individuals, having normal or slender increase in levels of serum bilirubin. Prompted by the dynamic interaction between bilirubin and bovine serum albumin (BSA), bilirubin-BSA complex was explored as a biocompatible cap system for protease responsive delivery device of anticancer drug against colon cancer. Bilirubin, conjugated to the amine terminated and doxorubicin loaded mesoporous silica nanoparticles were employed as a novel formulation against colon carcinoma cells. Compared to doxorubicin only, bilirubin in combination with doxorubicin-loaded mesoporous silica nanoparticle significantly inhibits tumor cell growth as assessed in MC-38 (murine) and HCT-116 (human) colon cancer cells. Bilirubin-doxorubicin combination potently inhibits proliferation of tumor cells and acted as cytotoxic and pro-apoptotic agent in vitro. Our result demonstrates that this novel cap system could play a precise role in defense against colon cancer by interrupting the pro-cancerogenic survival pathways during carcinogenesis.

Hydrazine as a hydrogen carrier in the photocatalytic generation of H2 using CdS quantum dots.

The compelling need for safe storage and transportation of H2 has made liquid-phase materials safer H2-carriers with a high gravimetric and volumetric hydrogen density. Unlike thermal or electrocatalytic decomposition on precious metal catalysts, a photocatalytic route to decomposing these liquid-phase materials can offer triggered onboard production of H2 and help mitigate the safety issues concerned with H2 storage. We have investigated visible-light induced H2 evolution from aqueous hydrazine using CdS quantum dots (QDs) as metal-free photocatalysts. Hydrazine acts as a H2 carrier as well as a donor, giving rise to a visible-light induced H2 evolution activity as high as 33 mmol h-1 g-1 at pH 8. This has been achieved by the use of CdS QDs capped with S2- ligands. The use of larger ligands such as mercaptopropionic acid hinders the adsorption of hydrazine onto CdS QDs and significantly decreases the activity. The effect of pH on the hydrogen yield in aqueous hydrazine has also been examined.