Deciphering Charge Transfer Processes in Transition Metal Complexes from the Perspective of Ultrafast Electronic and Nuclear Motions.

Chemical transformations in charge transfer states result from the interplay between electronic dynamics and nuclear reorganization along excited-state trajectories. Here, we investigate the ultrafast structural dynamics following photoinduced electron transfer from the metal-metal-to-ligand charge transfer state of an electron donor, a Pt dimer complex, to a covalently linked electron acceptor group using ultrafast time-resolved wide-angle X-ray scattering and optical transient absorption spectroscopy methods to disentangle the interdependence of the excited-state electronic and nuclear dynamics. Following photoexcitation, Pt-Pt bond formation and contraction takes up to 1 ps, much slower than the corresponding process in analogous complexes without electron acceptor groups. Because the Pt-Pt distance change is slow with respect to excited-state electron transfer, it can affect the rate of electron transfer. These results have potential impacts on controlling electron transfer rates via structural alterations to the electron donor group, tuning the charge transfer driving force.

Lysophosphatidylserine: A Signaling Lipid with Implications in Human Diseases.

Lysophosphatidylserine (lyso-PS) has emerged as yet another important signaling lysophospholipid in mammals, and deregulation in its metabolism has been directly linked to an array of human autoimmune and neurological disorders. It has an indispensable role in several biological processes in humans, and therefore, cellular concentrations of lyso-PS are tightly regulated to ensure optimal signaling and functioning in physiological settings. Given its biological importance, the past two decades have seen an explosion in the available literature toward our understanding of diverse aspects of lyso-PS metabolism and signaling and its association with human diseases. In this Review, we aim to comprehensively summarize different aspects of lyso-PS, such as its structure, biodistribution, chemical synthesis, and SAR studies with some synthetic analogs. From a biochemical perspective, we provide an exhaustive coverage of the diverse biological activities modulated by lyso-PSs, such as its metabolism and the receptors that respond to them in humans. We also briefly discuss the human diseases associated with aberrant lyso-PS metabolism and signaling and posit some future directions that may advance our understanding of lyso-PS-mediated mammalian physiology.

A new Eosin Y-based 'turnon' fluorescent sensor for ratiometric sensing of toxic mercury ion (Hg2+) offering unaided eye detection and its antibacterial activity.

A unique fluorescent molecule (ND-S) was obtained from Eosin Y in two simple yet high yielding steps (1). ND-S has special metal ion sensing ability, such that it can selectively detect toxic Hg2+ present in very low concentration in aqueous solutions in the presence of other competing metal ions. The host-guest complexation is ratiometric and is associated with significant increase in fluorescence during the process. Isothermal titration calorimetry (ITC) experiments provided thermodynamic parameters related to interaction between ND-S and Hg2+. Using inductively coupled plasma mass spectrometry (ICP-MS), the Hg2+(aq) removal efficiency of ND-S was estimated to be 99.88%. Appreciable limit of detection (LOD = 7.4 nM) was observed. Other competing ions did not interfere with the sensing of Hg2+ by ND-S. The effects of external stimuli (temperature and pH) were studied. Besides, the complex (ND-M), formed by 1:1 coordination of ND-S and Hg2+ was found to be effective against the survival of Gram-positive bacteria (S. aureus and B. subtilis) with a high selectivity index. Moreover, bacterial cell death mechanism was studied systematically. Overall, we have shown the transformation of a toxic species (Hg2+), extracted from polluted water by a biocompatible sensor (ND-S), into an effective and potent antibacterial agent (ND-M).

Metabolic transitions regulate global protein fatty acylation.

Intermediary metabolites and flux through various pathways have emerged as key determinants of post-translational modifications. Independently, dynamic fluctuations in their concentrations are known to drive cellular energetics in a bi-directional manner. Notably, intracellular fatty acid pools that drastically change during fed and fasted states act as precursors for both ATP production and fatty acylation of proteins. Protein fatty acylation is well regarded for its role in regulating structure and functions of diverse proteins; however, the effect of intracellular concentrations of fatty acids on protein modification is less understood. In this regard, we unequivocally demonstrate that metabolic contexts, viz. fed and fasted states, dictate the extent of global fatty acylation. Moreover, we show that presence or absence of glucose that influences cellular and mitochondrial uptake/utilization of fatty acids and affects palmitoylation and oleoylation, which is consistent with their intracellular abundance in fed and fasted states. Employing complementary approaches including click-chemistry, lipidomics, and imaging, we show the top-down control of cellular metabolic state. Importantly, our results establish the crucial role of mitochondria and retrograde signaling components like SIRT4, AMPK, and mTOR in orchestrating protein fatty acylation at a whole cell level. Specifically, pharmacogenetic perturbations that alter either mitochondrial functions and/or retrograde signaling affect protein fatty acylation. Besides illustrating the cross-talk between carbohydrate and lipid metabolism in mediating bulk post-translational modification, our findings also highlight the involvement of mitochondrial energetics.

A Case of Myoepithelioma of Nasal Cavity and Short Review of Literature.

Introduction: Myoepithelioma is a rare neoplasm of the salivary glands and accounts for less than 1% of salivary gland neoplasms. Only 7 cases of myoepithelioma in the nasal cavity have been reported till date in literature. Case Report: A 61 year old male presented to us with epistaxis. There was a pinkish fleshy mass occupying the right nasal cavity. Biopsy showed evidence of an epithelial tumor of intermediate aggressiveness. We did an endoscopic complete excision of nasal cavity mass. Histopathological examination of the resected tumor was consistent with myoepithelioma. Due to its rarity, the nature of the tumor is not known and regular follow-ups are needed for early detection of recurrence and malignancy. There has been no evidence of tumor recurrence in the 18 months following surgery.

Collision Tumour of Combined Neuroendocrine and Squamous Cell Carcinoma of Nasal Cavity and Paranasal Sinus- Case Report and Review of Literature.

Background: There have been many disputes about the definition, diagnosis, therapy, and prognosis of collision tumours. Case Summary: We describe a rare patient with a collision tumour consisting of high-grade neuroendocrine carcinoma (NEC) and squamous cell carcinoma (SCC) in the right nasal cavity and paranasal sinus. She received surgery, concurrent chemoradiotherapy, and then two cycles of palliative chemotherapy. Follow-up at 26 months after diagnosis showed that this patient experienced a complete response with no signs of recurrence or metastasis. A literature review of previous 27 cases diagnosed with collision tumour of NEC and SCC in the head and neck was also undertaken. Conclusion: It is highly challenging to manage collision tumours because these are two morphologically and etiologically distinct tumours. Well-designed multimodality therapy including surgery and chemoradiotherapy might lead to a long survival in these patients.

Cutaneous Radiation-Associated Angiosarcoma After Treatment of Carcinoma Penis: First Report from Tertiary Cancer Centre of North India.

Cutaneous radiation-associated angiosarcoma (cRAA) is a rare and aggressive secondary cutaneous angiosarcoma (cAS) with poor survival. cRAA has been mostly reported in breast carcinoma patients. Owing to its rarity, there is scanty literature available and no treatment guidelines. To the best of our knowledge, this is the first report of cRAA after multimodality treatment of carcinoma penis. A sixty-eight-year-old gentleman, a known case of carcinoma penis, underwent total penectomy with perineal urethrostomy and bilateral radical inguinopelvic lymph node dissection 6 years ago. He received adjuvant radiotherapy to the pelvis and bilateral groin. He presented with a bleeding plaque-like lesion with ulceration over the left lower abdomen (within previous radiation field) which rapidly progressed in size over the past 2 months. On examination, the lesion bled profusely on touch. Contrast MRI was suggestive of lobulated exophytic enhancing cutaneous lesion free from underlying muscle. Wedge biopsy was suggestive of cutaneous angiosarcoma. He underwent wide local excision with local perforator flap reconstruction from the right lower abdomen. Histopathology was suggestive of cutaneous angiosarcoma which showed immunoexpression of CD31, ERG1, cMYC suggestive of cRAA. cRAA is a very aggressive disease with 5-year survival of 15-34%. To the best of our knowledge, this is the first ever reported case of cRAA of lower abdomen after multimodality management of carcinoma penis. It masquerades with other benign and less aggressive radiation-induced skin lesions. cMYC immunoexpression is specific for secondary cAS. Wide local resection with negative margin provides the best outcome.

Enzalutamide-Induced Acute Maculopapular Rash in Treatment of Metastatic Prostate Cancer: First Case Report from a Tertiary Cancer Care Center of North India.

Enzalutamide is a new potent inhibitor of the signaling pathway for the androgen receptor with a half-life of 5.8 days. It has been on the market for the treatment of metastatic castration-resistant prostate cancer since November 2013. We report a case of acute generalized exanthematous maculopapular rash induced by enzalutamide. In summary, newer androgen receptor blockers have a propensity to cause skin related adverse effects. Most common among these are apalutamide. Enzalumatamide, per se, is a safe drug and has not been associated frequently in causing maculopapular rash. Few cases has been reported. In all these cases, the drug was discontinued and 2nd line therapy was instituted. In this report, Enzalutamide was withheld for 10 days and anti-histaminics was instituted. After a full recovery, Enzalutamide was reinstituted in treatment. A 62-year-old male patient with no significant medical history, was diagnosed in March 2020 with metastatic prostatic adenocarcinoma. Baseline PSA was 456 ng/ml. PSMA PET scan showed evidence of multiple bony metastasis. He was started on Degarelix subcutaneous injection with oral abiraterone initially. PSA level showed initial decreasing trend till September 2021 followed by sudden increase. Intramuscular Injection leuprolide was started and initial responses were good followed by later rise of PSA from January. Tab Xtandi (Enzalutamide) was added to the regimen from 31.1.22. Three days after starting enzalutamide treatment, the patient experienced an acute skin reaction. It is about of the plaques covered with widespread millimetric non-follicular papules. Enzalutamide was stopped after appearance of rashes to avoid further serious adverse effects. Anti-histaminics were started. Complete resolution of skin lesions occurred within 10 days. Tab Enzalutamide was reinstituted on 11th day after stoppage and on complete resolution of skin resolutions. According to the CTCAE 5.0 criteria, these skin rash was graded as grade 2. In view of evidence in literature and clinical improvement after stoppage, the acute drug reaction was attributed to enzalutamide. Uro oncologist can be confronted with adverse skin drug reactions attributable to new therapeutic molecules. The slow resolution of symptoms seems be due to the long half-life of enzalutamide. It should not be withdrawn from therapy owing to these effects. Rather, it should be with stopped for 10-14 days. Basic treatment with anti-histaminics or topical steroids may be enough to warranty the resolution of symptoms, and the drug (Enzalutamide) can be continued thereafter.

Extremely Rare Case of Extra Skeletal Soft Tissue Chondroma of Masseteric Space: a Diagnostic Challengel.

Benign soft tissue chondroma is a rare type of extraskeletal chondrocytic tumour. It usually can be found in skeletal system in extremities. Head and neck region is one of the most uncommon sites for extraskeletal chondroma .Most common site is tongue and there has been paucity of cases arising from the other subsites .We present a case of 56 years gentleman who came to our OPD with a right masticator space swelling. It was nonmalignant on FNAC. He underwent wide local excision through a transparotid approach. Final biopsy & IHC report showed presence of benign chondrocytic neoplasm- soft tissue chondroma (extraskeletal). No further therapy was used and he has been in follow up since then. To our knowledge ,this is the third reported case of masseteric space chondroma. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03705-5.

Metabolic regulation of CTCF expression and chromatin association dictates starvation response in mice and flies.

Coordinated temporal control of gene expression is essential for physiological homeostasis, especially during metabolic transitions. However, the interplay between chromatin architectural proteins and metabolism in regulating transcription is less understood. Here, we demonstrate a conserved bidirectional interplay between CTCF (CCCTC-binding factor) expression/function and metabolic inputs during feed-fast cycles. Our results indicate that its loci-specific functional diversity is associated with physiological plasticity in mouse hepatocytes. CTCF differential expression and long non-coding RNA-Jpx mediated changes in chromatin occupancy, unraveled its paradoxical yet tuneable functions, which are governed by metabolic inputs. We illustrate the key role of CTCF in controlling temporal cascade of transcriptional response, with effects on hepatic mitochondrial energetics and lipidome. Underscoring the evolutionary conservation of CTCF-dependent metabolic homeostasis, CTCF knockdown in flies abrogated starvation resistance. In summary, we demonstrate the interplay between CTCF and metabolic inputs that highlights the coupled plasticity of physiological responses and chromatin function.

Revealing Excited-State Trajectories on Potential Energy Surfaces with Atomic Resolution in Real Time.

Photoexcited molecular trajectories on potential energy surfaces (PESs) prior to thermalization are intimately connected to the photochemical reaction outcome. The excited-state trajectories of a diplatinum complex featuring photo-activated metal-metal σ-bond formation and associated Pt-Pt stretching motions were detected in real time using femtosecond wide-angle X-ray solution scattering. The observed motions correspond well with coherent vibrational wavepacket motions detected by femtosecond optical transient absorption. Two key coordinates for intersystem crossing have been identified, the Pt-Pt bond length and the orientation of the ligands coordinated with the platinum centers, along which the excited-state trajectories can be projected onto the calculated PESs of the excited states. This investigation has gleaned novel insight into electronic transitions occurring on the time scales of vibrational motions measured in real time, revealing ultrafast nonadiabatic or non-equilibrium processes along excited-state trajectories involving multiple excited-state PESs.

SNAP@CQD as a promising therapeutic vehicle against HCoVs: An overview.

This report discusses potential therapies for treating human coronaviruses (HCoVs) and their economic impact. Specifically, we explore therapeutics that can support the body's immune response, including immunoglobulin (Ig)A, IgG and T-cell responses, to inhibit the viral replication cycle and improve respiratory function. We hypothesize that carbon quantum dots conjugated with S-nitroso-N-acetylpenicillamine (SNAP) could be a synergistic alternative cure for treating respiratory injuries caused by HCoV infections. To achieve this, we propose developing aerosol sprays containing SNAP moieties that release nitric oxide and are conjugated onto promising nanostructured materials. These sprays could combat HCoVs by inhibiting viral replication and improving respiratory function. Furthermore, they could potentially provide other benefits, such as providing novel possibilities for nasal vaccines in the future.

Robot-assisted retroperitoneal lymph node dissection for post-chemotherapy residual mass in testicular cancer: Long-term experience from a tertiary care centre.

Objectives: To present our intermediate to long-term oncological and functional outcomes of robot-assisted retroperitoneal lymph node dissection (RA-RPLND) in post-chemotherapy (PC) residual mass in testicular cancers. To the best of our knowledge, this is the largest single-centre experience of RA-RPLND for in such setting. Methods: Prospectively maintained database of carcinoma testis patients undergoing RA-RPLND from February 2012 to September 2021 was reviewed. Patient demographics, tumour stage and risk groups and chemotherapy details were recorded. Intraoperative details and post-operative complications were also noted. Pathological outcomes included were lymph node yield and histopathology report. Further, follow-up was done for recurrence and antegrade ejaculation status. Results: Total of 37 cases were done for PC residual masses. International germ cell cancer collaborative group good, intermediate and poor risk proportion was 18 (48.6%), 14 (37.8%) and 5 (13.5%), respectively. Bilateral full template dissection, unilateral modified template dissection and residual mass excision was performed in 59.5% (22/37), 35.1% (13/37) and 5.4% (2/37) patients, respectively. The median size of the excised residual mass was 3.45 cm interquartile range (IQR 2-6 cm), with the largest being 9 cm. The median lymph nodal yield was 19. The most common histology was necrosis (n = 24, 65%), followed by teratoma (n = 11, 30%) and viable malignancy (n = 2, 5%). Antegrade ejaculation was reported in 32 patients (86.4%). After a median follow-up of 41 (IQR 14-64) months, only one patient had a recurrence. Conclusions: RA-PC-RPLND is thus a safe, feasible and oncologically effective option for selected patients. With increasing experience, larger masses can also be dealt with efficiently.

Benchmarking the semi-stochastic CC(P;Q) approach for singlet-triplet gaps in biradicals.

We recently proposed a semi-stochastic approach to converging high-level coupled-cluster (CC) energetics, such as those obtained in the CC calculations with singles, doubles, and triples (CCSDT), in which the deterministic CC(P;Q) framework is merged with the stochastic configuration interaction Quantum Monte Carlo propagations [J. E. Deustua, J. Shen, and P. Piecuch, Phys. Rev. Lett. 119, 223003 (2017)]. In this work, we investigate the ability of the semi-stochastic CC(P;Q) methodology to recover the CCSDT energies of the lowest singlet and triplet states and the corresponding singlet-triplet gaps of biradical systems using methylene, (HFH)-, cyclobutadiene, cyclopentadienyl cation, and trimethylenemethane as examples.

Exploring the Role of Carbon-Based Nanomaterials in Microalgae for the Sustainable Production of Bioactive Compounds and Beyond.

An enchanting yet challenging task is the development of higher productivity in plants to meet the ample food demands for the growing global population while harmonizing the ecosystem using front-line technologies. This has kindled the practice of green microalgae cultivation as a driver of key biostimulant products, targeting agronomic needs. To this end, a prodigious and economical strategy for producing bioactive compounds (sources of secondary metabolites) from microalgae using carbon-based nanomaterials (CNMs) as a platform can circumvent these hurdles. Recently, the nanobionics approach of incorporating CNMs with living systems has emerged as a promising technique to develop organelles with new and augmented functions. Herein, we discuss the importance of 2D carbon nanosheets (CNS) as an alternative carbon source for the phototrophic cultivation of microalgae. CNS not only aids in cost reduction for algal cultivation but also confers combinatorial innate or exogenous functions that enhance its programmed biosynthetic metabolism, proliferation, or tolerance to stress. Moreover, the inherent ability of CNS to act as efficient biocatalysts can enhance the rate of photosynthesis. The primary focus of this mini-review is the development of an economic route for enhanced yield of bioactive compounds while simultaneously serving as a heterogeneous platform for enhancing the sustainable production of biostimulants including bioactive compounds from algal biomass for pharmaceutical and nutraceutical applications.

Electrochemical, Photophysical, Morphological and DFT Study of Polymorphic Sn(IV)-Porphyrins Containing Fluorinated Axial Ligand.

In this study, we report the polymorphism of six coordinated Sn(IV)- tetrabromophenyl porphyrins axially armed with fluorine-substituted phenolate ligands (structural formula [Sn(TBrPP)2+ (A- )2 ], where A is the axial ligand=3,5-difluoro phenol, compound 1). One form stabilizes in triclinic system (namely, 1α), and the other stabilizes in monoclinic system (namely, 1ß). The two 1α and 1ß polymorphs display distinct photophysical and morphological properties in the solid state. X-ray diffraction study reveals that these polymorphs 1α and 1ß significantly differ in their supramolecular architecture, different axial phenolate conformations, and noncovalent interactions, which are responsible for their distinct solid-state properties. The crystal packing of these polymorphs dominates by intermolecular C-H⋅⋅⋅F, C-H⋅⋅⋅π and C-Br⋅⋅⋅F interhalogen interactions. Furthermore, the solid-state emission spectra of 1α showed red-shifted emission bands with respect to 1ß, in addition the redox behavior of 1α is slightly different in comparison to 1ß. Complementary theoretical studies with Hirshfeld surface analysis show the definite role of Br⋅⋅⋅F interhalogen interactions in the overall stability. Mapping the electrostatic potential isosurfaces with the aid of density functional theory in compound 1 clearly shows the presence of σ-hole, a requisite feature to show halogen interactions in the crystalline state. In addition, lattice energy and single point energy calculation shows that 1α was found to be energetically more favorable and thermodynamically more stable compare to 1ß.

Affecting behavioural change through empowerment: conceptual insights from theory and agricultural case studies in South Asia.

Affecting behavioural change is a common underlying goal across environmental and agricultural sciences, from climate change mitigation and adaptation, biodiversity conservation, water management, to crop diversification. However, many projects fail to drive or sustain change despite sound science and good intentions. This paper draws on existing theories of behavioural change to construct a conceptual framework that explores pathways to initiate and sustain change through the lens of empowerment, self-efficacy and agency. The framework is demonstrated with case studies from a project in India and Bangladesh that examined social inclusion of marginalised and poor farmers in the context of intensifying agriculture. The framework and case studies highlight that a number of conditions are needed to affect meaningful change including that target beneficiaries are suitably motivated, believe in their own capability and power to enact change and have access to the necessary resources. We propose the framework as a tool to help project teams explore the underlying elements of the process of change when designing, implementing and assessing agricultural or environmental projects and interventions. We contend that behavioural and social change needs to be explicitly fostered in such endeavours to achieve better and longer-term outcomes for the people and environment. Supplementary Information: The online version contains supplementary material available at 10.1007/s10113-022-01939-7.

Deep Phenotypic Cell Classification using Capsule Neural Network.

Recent developments in ultra-high-throughput microscopy have created a new generation of cell classification methodologies focused solely on image-based cell phenotypes. These image-based analyses enable morphological profiling and screening of thousands or even millions of single cells at a fraction of the cost. They have been shown to demonstrate the statistical significance required for understanding the role of cell heterogeneity in diverse biologists. However, these single-cell analysis techniques are slow and require expensive genetic/epigenetic analysis. This treatise proposes an innovative DL system based on the newly created capsule networks (CapsNet) architecture. The proposed deep CapsNet model employs "Capsules" for high-level feature abstraction relevant to the cell category. Experiments demonstrate that our proposed system can accurately classify different types of cells based on phenotypic label-free bright-field images with over 98.06% accuracy and that deep CapsNet models outperform CNN models in the prior art.

A molecular vision of fungal cell wall organization by functional genomics and solid-state NMR.

Vast efforts have been devoted to the development of antifungal drugs targeting the cell wall, but the supramolecular architecture of this carbohydrate-rich composite remains insufficiently understood. Here we compare the cell wall structure of a fungal pathogen Aspergillus fumigatus and four mutants depleted of major structural polysaccharides. High-resolution solid-state NMR spectroscopy of intact cells reveals a rigid core formed by chitin, ß-1,3-glucan, and α-1,3-glucan, with galactosaminogalactan and galactomannan present in the mobile phase. Gene deletion reshuffles the composition and spatial organization of polysaccharides, with significant changes in their dynamics and water accessibility. The distribution of α-1,3-glucan in chemically isolated and dynamically distinct domains supports its functional diversity. Identification of valines in the alkali-insoluble carbohydrate core suggests a putative function in stabilizing macromolecular complexes. We propose a revised model of cell wall architecture which will improve our understanding of the structural response of fungal pathogens to stresses.

Excited-State Bond Contraction and Charge Migration in a Platinum Dimer Complex Characterized by X-ray and Optical Transient Absorption Spectroscopy.

Interactions between metal centers in dimeric transition metal complexes (TMCs) play important roles in their excited-state energetics and pathways and, thus, affect their photophysical properties relevant to their applications, for example, photoluminescent materials and photocatalysis. Here, we report electronic and nuclear structural dynamics studies of two photoexcited pyrazolate-bridged [Pt(ppy)(µ-R2pz)]2-type Pt(II) dimers (ppy = 2-phenylpyridine, µ-R2pz = 3,5-substituted pyrazolate): [Pt(ppy)(µ-H2pz)]2 (1) and [Pt(NDI-ppy)(µ-Ph2pz)]2 (2, NDI = 1,4,5,8-naphthalenediimide), both of which have distinct ground-state Pt-Pt distances. X-ray transient absorption (XTA) spectroscopy at the Pt LIII-edge revealed a new d-orbital vacancy due to the one-electron oxidation of the Pt centers in 1 and 2. However, while a transient Pt-Pt contraction was observed in 2, such an effect was completely absent in 1, demonstrating how the excited states of these complexes are determined by the overlap of the Pt (dz2) orbitals, which is tuned by the steric bulk of the pyrazolate R-groups in the 3- and 5-positions. In tandem with analysis of the Pt-Pt distance structural parameter, we observed photoinduced electron transfer in 2 featuring a covalently linked NDI acceptor on the ppy ligand. The formation and subsequent decay of the NDI radical anion absorption signals were detected upon photoexcitation using optical transient absorption spectroscopy. The NDI radical anion decayed on the same time scale, hundreds of picoseconds, as that of the d-orbital vacancy signal of the oxidized Pt-Pt core observed in the XTA measurements. The data indicated an ultrafast formation of the charge-separated state and subsequent charge recombination to the original Pt(II-II) species.