Revealing the therapeutic properties of gut microbiota: transforming cancer immunotherapy from basic to clinical approaches.

The immune system plays a pivotal role in the battle against cancer, serving as a formidable guardian in the ongoing fight against malignant cells. To combat these malignant cells, immunotherapy has emerged as a prevalent approach leveraging antibodies and peptides such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 to inhibit immune checkpoints and activate T lymphocytes. The optimization of gut microbiota plays a significant role in modulating the defense system in the body. This study explores the potential of certain gut-resident bacteria to amplify the impact of immunotherapy. Contemporary antibiotic treatments, which can impair gut flora, may diminish the efficacy of immune checkpoint blockers. Conversely, probiotics or fecal microbiota transplantation can help re-establish intestinal microflora equilibrium. Additionally, the gut microbiome has been implicated in various strategies to counteract immune resistance, thereby enhancing the success of cancer immunotherapy. This paper also acknowledges cutting-edge technologies such as nanotechnology, CAR-T therapy, ACT therapy, and oncolytic viruses in modulating gut microbiota. Thus, an exhaustive review of literature was performed to uncover the elusive link that could potentiate the gut microbiome's role in augmenting the success of cancer immunotherapy.

Porous Organic Polymers for Efficient and Selective SO2 Capture from CO2-rich Flue Gas.

The quest for effective technologies to reduce SO2 pollution is crucial due to its adverse effects on the environment and human health. Markedly, removing a ppm level of SO2 from CO2-containing waste gas is a persistent challenge, and current technologies suffer from low SO2/CO2 selectivity and energy-intensive regeneration processes. Here using the molecular building blocks approach and theoretical calculation, we constructed two porous organic polymers (POPs) encompassing pocket-like structures with exposed imidazole groups, promoting preferential interactions with SO2 from CO2-containing streams. Markedly, the evaluated POPs offer outstanding SO2/CO2 selectivity, high SO2 capacity, and an easy regeneration process, making it one of the best materials for SO2 capture. To gain better structural insights into the notable SO2 selectivity of the POPs, we used dynamic nuclear polarization NMR spectroscopy (DNP) and molecular modelling to probe the interactions between SO2 and POP adsorbents. The newly developed materials are poised to offer an energy-efficient and environment-friendly SO2 separation process while we are obliged to use fossil fuels for our energy needs.

A review exploring the fusion of oncolytic viruses and cancer immunotherapy: An innovative strategy in the realm of cancer treatment.

Oncolytic viruses (OVs) are increasingly recognized as potent tools in cancer therapy, effectively targeting and eradicating oncogenic conditions while sparing healthy cells. They enhance antitumor immunity by triggering various immune responses throughout the cancer cycle. Genetically engineered OVs swiftly destroy cancerous tissues and activate the immune system by releasing soluble antigens like danger signals and interferons. Their ability to stimulate both innate and adaptive immunity makes them particularly attractive in cancer immunotherapy. Recent advancements involve combining OVs with other immune therapies, yielding promising results. Transgenic OVs, designed to enhance immunostimulation and specifically target cancer cells, further improve immune responses. This review highlights the intrinsic mechanisms of OVs and underscores their synergistic potential with other immunotherapies. It also proposes strategies for optimizing armed OVs to bolster immunity against tumors.

A review on comprehending immunotherapeutic approaches inducing ferroptosis: Managing tumour immunity.

Ferroptosis, a necrotic, iron-dependent controlled cell death mechanism, is distinguished by the development of lipid peroxides to fatal proportions. Malignant tumours, influenced by iron to promote fast development, are vulnerable to ferroptosis. Based upon mounting evidence it has been observed that ferroptosis may be immunogenic and hence may complement immunotherapies. A new approach includes iron oxide-loaded nano-vaccines (IONVs), having supremacy for the traits of the tumour microenvironment (TME) to deliver specific antigens through improving the immunostimulatory capacity by molecular disintegration and reversible covalent bonds that target the tumour cells and induce ferroptosis. Apart from IONVs, another newer approach to induce ferroptosis in tumour cells is through oncolytic virus (OVs). One such oncolytic virus is the Newcastle Disease Virus (NDV), which can only multiply in cancer cells through the p53-SLC7A11-GPX4 pathway that leads to elevated levels of lipid peroxide and intracellular reactive oxygen species leading to the induction of ferroptosis that induce ferritinophagy.

A discrete magno-parvo additive model in early vision for explaining brightness perception in varying contrastive contexts.

A varying contrastive context filter (VCCF)-based model of brightness perception has been proposed. It is motivated first by a recently proposed difference of difference-of-Gaussian (DDOG) filter. Alongside, it is also inspired from the fact that the nature evolves various discrete systems and mechanisms to carry out many of its complex tasks. A weight factor, used for the linear combination of two filters representing the magnocellular and parvocellular channels in the central visual pathway, has been defined and termed as the factor of contrastive context (FOCC) in the present model. This is a binary variable that lends a property of discretization to the DDOG filter. By analyzing important brightness contrast as well as brightness assimilation illusions, we arrive at the minimal set of values (only two) for FOCC, using which one is able to successfully predict the direction of brightness shift in both situations of brightness contrast, claimed and categorized here as low contrastive context, and those of brightness assimilation, claimed and categorized here as high contrastive context perception, depending upon whether the initial M-channel-filtered stimulus is above or below a threshold of the contrastive context. As distinct from Michelson/Weber/RMS contrast, high or low, the contrastive context claimed is dependent on the edge information in the stimulus determined by the Laplacian operator, also used in the DDOG model. We compared the proposed model against the already well-established oriented difference-of-Gaussian (ODOG) model of brightness perception. Extensive simulations suggest that though for most illusions both ODOG and VCCF produce correct output, for certain intricate cases in which the ODOG filter fails to correctly predict the illusory effect, our proposed VCCF model continues to remain effective.

Intermediate Binding Control Using Metal-Organic Frameworks Enhances Electrochemical CO2 Reduction.

In the electrochemical CO2 reduction reaction (CO2RR), control over the binding of intermediates is key for tuning product selectivity and catalytic activity. Here we report the use of reticular chemistry to control the binding of CO2RR intermediates on metal catalysts encapsulated inside metal-organic frameworks (MOFs), thereby allowing us to improve CO2RR electrocatalysis. By varying systematically both the organic linker and the metal node in a face-centered cubic (fcu) MOF, we tune the adsorption of CO2, pore openness, and Lewis acidity of the MOFs. Using operando X-ray absorption spectroscopy (XAS) and in situ Raman spectroscopy, we reveal that the MOFs are stable under operating conditions and that this tuning plays the role of optimizing the *CO binding mode on the surface of Ag nanoparticles incorporated inside the MOFs with the increase of local CO2 concentration. As a result, we improve the CO selectivity from 74% for Ag/Zr-fcu-MOF-1,4-benzenedicarboxylic acid (BDC) to 94% for Ag/Zr-fcu-MOF-1,4-naphthalenedicarboxylic acid (NDC). The work offers a further avenue to utilize MOFs in the pursuit of materials design for CO2RR.

Made-to-order porous electrodes for supercapacitors: MOFs embedded with redox-active centers as a case study.

In this work, a pre-designed Zr-based-MOF encompassing an organic linker with a redox active core is synthesized and its structure-property relationship as a supercapacitor electrode is investigated. An enhanced performance is revealed by the combination of this MOF's high porosity and redox core incorporation, which alters its double-layer and pseudocapacitance, respectively. An increase in the capacitance performance by a factor of two is achieved via post-synthetic structure rigidification using organic pillars.

Iron-Induced Apoptotic Cell Death and Autophagy Dysfunction in Human Neuroblastoma Cell Line SH-SY5Y.

Iron accumulation plays a major role in neuronal cell death which has severe effects on mental health like neurodegenerative disorders. The present work aims to explore the involvement of molecular pathways involved in iron-mediated neuronal cell death using Ferric Ammonium Citrate (FAC) as a source of iron to treat neuroblastoma SH-SY5Y cells. In this study, it was found that cytotoxicity induced by iron treatment is highly correlated with enhanced intracellular reactive oxygen species (ROS) generation and loss of mitochondrial integrity. Appearance of early and late apoptotic cells with altered nuclear morphology and increased expression of effector proteins, i.e., cleaved Caspase 3 and cleaved PARP (Poly-ADP-ribose Polymerase), clearly confirmed iron-induced apoptotic cell deaths. Furthermore, excess accumulation of acidic vesicles and microtubule-associated protein 1 light chain 3 (LC3) puncta and LC3II/I expressions were observed. Simultaneously, ultrastructural studies of SH-SY5Y cells demonstrated the accumulation of a large number of autophagosomes, autophagic vacuolization, and swollen mitochondria which further confirmed the induction of autophagy concomitant with mitochondrial damage. Furthermore, increased incorporation of lysosome-specific dye, LysoTracker Deep Red, and the red fluorescence retention of LC3-GFP-RFP constructs indicates the incomplete autophagy or autophagy dysfunction due to altered lysosomal activity. Hence, the present work unveiled the interruption in autophagy progression caused by the plausible suppression of lysosomal activity due to iron treatment resulting in autophagic cell death in SH-SY5Y cell lines. In general, both apoptotic and autophagic pathways were prominent and each of the pathways played their prospective roles, in iron-mediated neuronal cell death.

Outcome of surgery in neck of femur fracture patients with poor pre-fracture mobility.

BACKGROUND: Hip fractures are common with a UK incidence of over 70,000 cases and total healthcare costs of over £2 billion per year. Mortality rates of 10% at 30 days and up to 30% at 1-year have been reported. We wanted to assess the outcome of hip fracture surgery in patients with reduced pre-fracture mobility as this has not been exclusively studied previously. METHODS: We retrospectively reviewed 168 hip fracture patients with reduced pre-fracture mobility (wheelchair bound, bed bound, walking with 2 aids or a frame) who underwent hip fracture surgery at our institution between 2008 and 2013 using case notes, discharge letters, outpatient clinic letters and laboratory test results. Measured outcomes included 30-day renal, cardiac and respiratory morbidity as well as 30-day and 1-year mortality. RESULTS: Our study comprised 27% males and 73% females with a mean age of 82 years. The 30-day chest infection, acute renal failure and acute coronary syndrome rates were 26%, 7.7% and 4% respectively. In those patients who were either wheelchair or bed bound, 30-day and 1-year mortality rates were 11.8% and 52% respectively whereas in those who could mobilise with the help of 2 aids or frame, 30-day and 1-year mortality rates were 4.34% and 39.70% respectively. CONCLUSION: Our study highlighted increased 30-day and 1-year morbidity and mortality rates following hip fracture surgery with notable high rates of respiratory and renal complications in patients with reduced pre-fracture mobility. We would recommend pre- and postoperative optimisation with orthogeriatric review, chest physiotherapy and intravenous fluid hydration to reduce complication rates and improve morbidity and mortality.

MXene Derived Metal-Organic Frameworks.

Synthesis of nanoscale metal-organic frameworks (MOFs) is a highly challenging task because conventional soluble metal salt precursors are not easy to manipulate spatially, thus normally leading to bulk MOFs. In the present work, V2CTx MXene is demonstrated for the first time as a metal precursor to fabricate two-dimensional (2D) MOF nanosheets, whose thickness (6 to 18 nm) can be tuned by varying the reaction temperature. The highly electronegative surface atoms of MXene and sufficient accessible attacking sites for ligands are responsible for the evolution of 2D MOF nanosheets. Moreover, highly oriented and smooth MOF thin films have been grown based on these nanosheets using a convenient spin coating process. With the impregnation of nonvolatile H3PO4, the MOF thin film exhibits a proton-conducting property. This study demonstrates that high-quality 2D MOF sheets and thin films are enabled by 2D MXene precursors. We believe that the high-quality MOF films prepared in this study pave the way for many device applications.

Unprecedented Ultralow Detection Limit of Amines using a Thiadiazole-Functionalized Zr(IV)-Based Metal-Organic Framework.

A luminescent Zr(IV)-based metal-organic framework (MOF), with the underlying fcu topology, encompassing a π-conjugated organic ligand with a thiadiazole functionality, exhibits an unprecedented low detection limit of 66 nM for amines in aqueous solution. Markedly, this ultralow detection is driven by hydrogen-bonding interactions between the linker and the hosted amines. This observation is supported by density functional theory (DFT) calculations, which clearly corroborate the suppression of the twisting motion of thiadiazole core in the presence of amine, reducing significantly the nonradiative recombination pathways and subsequently enhancing the emission intensity. Credibly, nicotine regarded as a harmful chemical and bearing an amine pending group is also detected with high sensitivity, positioning this MOF as a potential sensor for practical environmental applications. This finding serves also as a benchmark to understand the sensing mechanism in MOFs.

Metal-Organic Framework Thin Films on High-Curvature Nanostructures Toward Tandem Electrocatalysis.

In tandem catalysis, two distinct catalytic materials are interfaced to feed the product of one reaction into the next one. This approach, analogous to enzyme cascades, can potentially be used to upgrade small molecules such as CO2 to more valuable hydrocarbons. Here, we investigate the materials chemistry of metal-organic framework (MOF) thin films grown on gold nanostructured microelectrodes (AuNMEs), focusing on the key materials chemistry challenges necessary to enable the applications of these MOF/AuNME composites in tandem catalysis. We applied two growth methods-layer-by-layer and solvothermal-to grow a variety of MOF thin films on AuNMEs and then characterized them using scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The MOF@AuNME materials were then evaluated for electrocatalytic CO2 reduction. The morphology and crystallinity of the MOF thin films were examined, and it was found that MOF thin films were capable of dramatically suppressing CO production on AuNMEs and producing further-reduced carbon products such as CH4 and C2H4. This work illustrates the use of MOF thin films to tune the activity of an underlying CO2RR catalyst to produce further-reduced products.

Covalent Organic Framework Material Bearing Phloroglucinol Building Units as a Potent Anticancer Agent.

Covalent organic frameworks (COFs) having periodicity in pores of nanoscale dimensions can be suitably designed for the organic building units bearing reactive functional groups at their surfaces. Thus, they are an attractive option as an anticancer agent to overcome the limitations of chemotherapy. Herein, we first report a new porous biodegradable nitrogen containing COF material, EDTFP-1 (ethylenedianiline-triformyl phloroglucinol), synthesized using 4,4'-ethylenedianiline and 2,4,6-triformylphloroglucinol via Schiff base condensation reaction. EDTFP-1 exhibited 3D-hexagonal porous structure with average pores of ca. 1.5 nm dimension. Here, we have explored the anticancer potentiality of EDTFP-1. Result demonstrated an enhanced cytotoxicity was observed against four cancer cells HCT 116, HepG2, A549, and MIA-Paca2 with significant lower IC50 on HCT116 cells. Additionally, EDTFP-1-induced cell death was associated with the characteristic apoptotic changes like cell membrane blebbing, nuclear DNA fragmentation, externalization of phosphatidylserine from the cell membrane followed by a loss of mitochondrial membrane potential as well as modulation of pro and antiapoptotic proteins. Further, the result depicted a direct correlation between the generations of ROS with mitochondrial-dependent apoptosis through the involvement of p53 phosphorylation upon EDTFP-1 induction, suggesting this COF material is a novel chemotherapeutic agent for cancer treatment.

Valuing Metal-Organic Frameworks for Postcombustion Carbon Capture: A Benchmark Study for Evaluating Physical Adsorbents.

The development of practical solutions for the energy-efficient capture of carbon dioxide is of prime importance and continues to attract intensive research interest. Conceivably, the implementation of adsorption-based processes using different cycling modes, e.g., pressure-swing adsorption or temperature-swing adsorption, offers great prospects to address this challenge. Practically, the successful deployment of practical adsorption-based technologies depends on the development of made-to-order adsorbents expressing mutually two compulsory requisites: i) high selectivity/affinity for CO2 and ii) excellent chemical stability in the presence of impurities. This study presents a new comprehensive experimental protocol apposite for assessing the prospects of a given physical adsorbent for carbon capture under flue gas stream conditions. The protocol permits: i) the baseline performance of commercial adsorbents such as zeolite 13X, activated carbon versus liquid amine scrubbing to be ascertained, and ii) a standardized evaluation of the best reported metal-organic framework (MOF) materials for carbon dioxide capture from flue gas to be undertaken. This extensive study corroborates the exceptional CO2 capture performance of the recently isolated second-generation fluorinated MOF material, NbOFFIVE-1-Ni, concomitant with an impressive chemical stability and a low energy for regeneration. Essentially, the NbOFFIVE-1-Ni adsorbent presents the best compromise by satisfying all the required metrics for efficient CO2 scrubbing.

Self-Exfoliated Metal-Organic Nanosheets through Hydrolytic Unfolding of Metal-Organic Polyhedra.

Few-layers thick metal-organic nanosheets have been synthesized using water-assisted solid-state transformation through a combined top-down and bottom-up approach. The metal-organic polyhedra (MOPs) convert into metal-organic frameworks (MOFs) which subsequently self-exfoliate into few-layered metal-organic nanosheets. These MOP crystals experience a hydrophobicity gradient with the inner surface during contact with water because of the existence of hydrophobic spikes on their outer surface. When the amount of water available for interaction is higher, the resultant layers are not stacked to form bulk materials; instead few-layered nanosheets with high uniformity were obtained in high yield. The phenomenon has resulted high yield production of uniformly distributed layered metal-organic nanosheets from three different MOPs, showing its general adaptability.

Limitations of the Oriented Difference of Gaussian Filter in Special Cases of Brightness Perception Illusions.

The Oriented Difference of Gaussian (ODOG) filter of Blakeslee and McCourt has been successfully employed to explain several brightness perception illusions which include illusions of both brightness-contrast type, for example, Simultaneous Brightness Contrast and Grating Induction and the brightness-assimilation type, for example, the White effect and the shifted White effect. Here, we demonstrate some limitations of the ODOG filter in predicting perceived brightness by comparing the ODOG responses to various stimuli (generated by varying two parameters, namely, test patch length and spatial frequency) with experimental observations of the same.

Photochromic metal-organic frameworks for inkless and erasable printing.

Inkless and erasable printing is the key solution towards a more sustainable paper industry, in terms of reducing paper wastages and the associated environmental hazards from waste paper processing. However, only a few cases have been reported in the literature where inkless printing has been tested in some practical systems. In an attempt to address this solution, we used photochromic metal-organic frameworks (MOFs) and tested their capability as inkless and erasable printing media. The printing was performed using sunlight as the light source on MOF-coated papers. The resulting printing had good resolution and stability, and was capable of being read both by the human eye and smart electronic devices; furthermore, the paper could be reused for several cycles without any significant loss in intensity. Interestingly, different coloured printing with a similar efficiency was achieved by varying the structure of the MOF.

Hollow tubular porous covalent organic framework (COF) nanostructures.

Hollow and tubular TpPa-COF structures have been synthesized by template-assisted replication of nanometer sized ZnO-nanorods. The hollow structures composed of microporous TpPa shells have high periodicity, moderate porosity, chemical stability and capsule shaped morphology as revealed by X-ray diffraction, porosity measurements, and SEM and TEM analyses.

Solid state organic amine detection in a photochromic porous metal organic framework.

A new Mg(ii) based photochromic porous metal-organic framework (MOF) has been synthesized bearing naphthalenediimide (NDI) chromophoric unit. This MOF (Mg-NDI) shows instant and reversible solvatochromic behavior in presence of solvents with different polarity. Mg-NDI also exhibits fast and reversible photochromism via radical formation. Due to the presence of electron deficient NDI moiety, this MOF exhibits selective organic amine (electron rich) sensing in solid state. The organic amine detection has been confirmed by photoluminescence quenching experiment and visual color change.

Gold(I)/chiral Brønsted acid catalyzed enantioselective hydroamination-hydroarylation of alkynes: the effect of a remote hydroxyl group on the reactivity and enantioselectivity.

The catalytic enantioselective hydroamination-hydroarylation of alkynes under the catalysis of (R3P)AuMe/(S)-3,3'-bis(2,4,6-triisopropylphenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate ((S)-TRIP) is reported. The alkyne was reacted with a range of pyrrole-based aromatic amines to give pyrrole-embedded aza-heterocyclic scaffolds bearing a quaternary carbon center. The presence of a hydroxyl group in the alkyne tether turned out to be very crucial for obtaining products in high yields and enantioselectivities. The mechanism of enantioinduction was established by carefully performing experimental and computational studies.