Unravelling the mechanism of polarization transfer from spin-1/2 to spin-1 system in solids.

An analytic theory based on the concept of "effective-fields" is proposed to explain the mechanism of polarization transfer from spin I = 1/2 to spin S = 1 in non-rotating (static) solids. Employing an isolated two-spin model system, the matching conditions responsible for polarization transfer in cross-polarization (CP) experiments are identified and described in terms of the single-transition operators. In contrast to other existing treatments, the polarization transfer among spins is quantified through analytic expressions highlighting the individual contributions emerging from all plausible CP matching conditions. The interplay between the CP matching conditions observed in experiments is outlined in both isotropic and anisotropic systems and verified through comparison between simulations based on analytic and exact numerical methods. The predictions emerging from the analytic theory are verified over a wide range of experimentally relevant parameters and could be beneficial in the optimization of the CP experiments.

Determination of the mutual orientation between proton CSA tensors mediated through band-selective 1H-1H recoupling under fast MAS.

The mutual orientation of nuclear spin interaction tensors provides critical information on the conformation and arrangement of molecules in chemicals, materials, and biological systems at an atomic level. Proton is a ubiquitous and important element in a variety of substances, and its NMR is highly sensitive due to their virtually 100% natural abundance and large gyromagnetic ratio. Nevertheless, the measurement of mutual orientation between the 1H CSA tensors has remained largely untouched in the past due to strong 1H-1H homonuclear interactions in a dense network of protons. In this study, we have developed a proton-detected 3D 1H CSA/1H CSA/1H CS correlation method that utilizes three techniques to manage homonuclear interactions, namely fast magic-angle spinning, windowless C-symmetry-based CSA recoupling (windowless-ROCSA), and a band-selective 1H-1H polarization transfer. The asymmetric 1H CSA/1H CSA correlated powder patterns produced by the C-symmetry-based methods are highly sensitive to the sign and asymmetry parameter of the 1H CSA, and the Euler angle ß as compared to the symmetric pattern obtained by the existing γ-encoded R-symmetry-based CSA/CSA correlation methods and allows a larger spectral area for data fitting. These features are beneficial for determining the mutual orientation between the nuclear spin interaction tensors with improved accuracy.

Uncovering the Lipid Web: Discovering the Multifaceted Roles of Lipids in Human Diseases and Therapeutic Opportunities.

Lipids, characterized by their hydrophobic nature, encompass a wide range of molecules with distinct properties and functions [...].

Fat and Protein Combat Triggers Immunological Weapons of Innate and Adaptive Immune Systems to Launch Neuroinflammation in Parkinson's Disease.

Parkinson's disease (PD) is the second-most common neurodegenerative disease in the world, affecting up to 10 million people. This disease mainly happens due to the loss of dopaminergic neurons accountable for memory and motor function. Partial glucocerebrosidase enzyme deficiency and the resultant excess accumulation of glycosphingolipids and alpha-synuclein (α-syn) aggregation have been linked to predominant risk factors that lead to neurodegeneration and memory and motor defects in PD, with known and unknown causes. An increasing body of evidence uncovers the role of several other lipids and their association with α-syn aggregation, which activates the innate and adaptive immune system and sparks brain inflammation in PD. Here, we review the emerging role of a number of lipids, i.e., triglyceride (TG), diglycerides (DG), glycerophosphoethanolamines (GPE), polyunsaturated fatty acids (PUFA), sphingolipids, gangliosides, glycerophospholipids (GPL), and cholesterols, and their connection with α-syn aggregation as well as the induction of innate and adaptive immune reactions that trigger neuroinflammation in PD.

Targeting the Complement-Sphingolipid System in COVID-19 and Gaucher Diseases: Evidence for a New Treatment Strategy.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced disease (COVID-19) and Gaucher disease (GD) exhibit upregulation of complement 5a (C5a) and its C5aR1 receptor, and excess synthesis of glycosphingolipids that lead to increased infiltration and activation of innate and adaptive immune cells, resulting in massive generation of pro-inflammatory cytokines, chemokines and growth factors. This C5a-C5aR1-glycosphingolipid pathway- induced pro-inflammatory environment causes the tissue damage in COVID-19 and GD. Strikingly, pharmaceutically targeting the C5a-C5aR1 axis or the glycosphingolipid synthesis pathway led to a reduction in glycosphingolipid synthesis and innate and adaptive immune inflammation, and protection from the tissue destruction in both COVID-19 and GD. These results reveal a common involvement of the complement and glycosphingolipid systems driving immune inflammation and tissue damage in COVID-19 and GD, respectively. It is therefore expected that combined targeting of the complement and sphingolipid pathways could ameliorate the tissue destruction, organ failure, and death in patients at high-risk of developing severe cases of COVID-19.

Bimodal Floquet theory of phase-modulated heteronuclear decoupling experiments in solid-state NMR spectroscopy.

A prescription based on bimodal Floquet theory is proposed to describe the nuances of phase-modulated supercycled decoupling experiments in solids. The frequency dependent interaction frames relevant to a particular supercycle are identified to facilitate faster convergence of perturbation corrections to the derived effective Hamiltonians. In contrast to silico-based methods, the proposed analytic method offers an attractive platform for faster optimization of experiments in solids. Additionally, the relevance of supercycling at ultrafast spinning conditions is also discussed.

C-X-C Motif Chemokine Ligand 9 and Its CXCR3 Receptor Are the Salt and Pepper for T Cells Trafficking in a Mouse Model of Gaucher Disease.

Gaucher disease is a lysosomal storage disease, which happens due to mutations in GBA1/Gba1 that encodes the enzyme termed as lysosomal acid ß-glucosidase. The major function of this enzyme is to catalyze glucosylceramide (GC) into glucose and ceramide. The deficiency of this enzyme and resultant abnormal accumulation of GC cause altered function of several of the innate and adaptive immune cells. For example, augmented infiltration of T cells contributes to the increased production of pro-inflammatory cytokines, (e.g., IFNγ, TNFα, IL6, IL12p40, IL12p70, IL23, and IL17A/F). This leads to tissue damage in a genetic mouse model (Gba19V/-) of Gaucher disease. The cellular mechanism(s) by which increased tissue infiltration of T cells occurs in this disease is not fully understood. Here, we delineate role of the CXCR3 receptor and its exogenous C-X-C motif chemokine ligand 9 (CXCL9) in induction of increased tissue recruitment of CD4+ T and CD8+ T cells in Gaucher disease. Intracellular FACS staining of macrophages (Mϕs) and dendritic cells (DCs) from Gba19V/- mice showed elevated production of CXCL9. Purified CD4+ T cells and the CD8+ T cells from Gba19V/- mice showed increased expression of CXCR3. Ex vivo and in vivo chemotaxis experiments showed CXCL9 involvement in the recruitment of Gba19V/- T cells. Furthermore, antibody blockade of the CXCL9 receptor (CXCR3) on T cells caused marked reduction in CXCL9- mediated chemotaxis of T cells in Gba19V/- mice. These data implicate abnormalities of the CXCL9-CXCR3 axis leading to enhanced tissue recruitment of T cells in Gaucher disease. Such results provide a rationale for blockade of the CXCL9/CXCR3 axis as potential new therapeutic targets for the treatment of inflammation in Gaucher disease.

Understanding charge carrier dynamics in a P3HT:FLR blend.

In organic semiconductors, optical absorption is pivotal for the performance of optoelectronic devices. The absorption by the semiconductors generates excitons which dissociate into free charge carriers, resulting in energy conversion. Although high performance has been achieved in non-fullerene organic solar cells, their charge generation behavior is far from being well understood. Keeping this in view, we have employed optical spectroscopic tools to study the charge generation mechanism in FLR (1,6,7,10-tetramethylfluoranthene) as a non-fullerene electron acceptor blended with P3HT (poly(3-hexylthiophene)) as an electron donor in five different solvents. Through steady state UV-visible and photoluminescence spectroscopy, we provide a basic understanding of charge transport by enlightening the influence of solvents on the aggregation behavior and exciton bandwidth. Furthermore, for the first time, by employing ultrafast vis-NIR transient absorption spectroscopy, we address the ultrafast charge generation and charge separation mechanism with systematic variation in solvent polarity by incorporating the time evolution of the transient species under various pump-probe wavelengths in the range of 450 nm to 1600 nm. For the different excitation wavelengths, the lifetime kinetics have been depicted by their multiexponential fits. The results show a fast decay term at a lifetime of a few picoseconds (ps) (∼1 to 5 ps) and a slow decay term at a lifetime of ∼500 ps. The charge generation in the P3HT:FLR blend proceeds on a ps time scale, which implies good intermixing of the components. It is clearly established that the non-halogenated solvents influence this aggregation behavior and higher conjugation lengths with higher photoluminescence quenching contribute to the higher charge generation. The enhanced polaron population in P3HT with the addition of FLR illustrates the importance of this acceptor material in the blend because a good solvent-material combination is essential to enhance the charge generation. As such, this comprehensive study explicitly shows the role of FLR as an emerging efficient non-fullerene acceptor for further improving the performance of devices.

Proton-detected 3D 1H anisotropic/14N/1H isotropic chemical shifts correlation NMR under fast magic angle spinning on solid samples without isotopic enrichment.

The chemical shift anisotropy (CSA) interaction of a nucleus is an important indicator of the local electronic environment particularly for the contributions arising from hydrogen (H)-bonding, electrostatic and π-π interactions. CSAs of protons bonded to nitrogen atoms are of significant interest due to their common role as H-bonding partners in many chemical, pharmaceutical and biological systems. Although very fast (∼100 kHz) magic angle sample spinning (MAS) experiments have enabled the measurement of proton CSAs directly from solids, due to a narrow chemical shift (CS) distribution, overlapping NH proton resonances are common and necessitate the introduction of an additional frequency dimension to the regular 2D 1H CSA/1H CS correlation method to achieve sufficient resolution. While this can be accomplished by using the isotropic shift frequency of 14N or 15N nuclei, the use of the naturally-abundant 14N nucleus avoids 15N isotopic labeling and therefore would be useful for a variety of solids. To this end, we propose a proton-detected 3D 1H CSA/14N/1H CS correlation method under fast MAS (90 kHz) to determine the CSA tensors of NH protons in samples without isotopic enrichment. Our experimental results demonstrate that the proposed 3D NMR experiment is capable of resolving the overlapping 1H resonances of amide (NH) groups through the 14N isotropic shift frequency dimension and enables the accurate measurement of site-specific 1H CSAs directly from powder samples under fast MAS conditions. In addition to the 3D 1H CSA/14N/1H CS experiment, an approach employing 14N-edited 2D 1H CSA/1H CS experiment is also demonstrated as an additional means to address spectral overlap of NH resonances with aliphatic and other proton resonances in solids.

Determination of the 15 N chemical shift anisotropy in natural abundance samples by proton-detected 3D solid-state NMR under ultrafast MAS of 70 kHz.

Chemical shift anisotropy (CSA) is a sensitive probe of electronic environment at a nucleus, and thus, it offers deeper insights into detailed structural and dynamic properties of different systems, for example, chemical, biological, and materials. Over the years, massive efforts have been made to develop recoupling methods that reintroduce CSA interaction under magic angle spinning (MAS) conditions. Most of them require slow or moderate MAS (≤20 kHz) and isotopically enriched samples. On the other hand, to the best of the authors' knowledge, no 13 C or 15 N CSA recoupling schemes at ultrafast MAS (≥60 kHz) suitable for cost-effective natural abundant samples have been developed. We present here a proton-detected 3D 15 N CS/15 N CSA/1 H CS correlation experiment which employs 1 H indirect detection for sensitivity enhancement and a γ-encoded RNnν -symmetry-based CSA recoupling scheme. In particular, two different symmetries, that is, R837 and R1049 , are first tested, in a 2D 15 N CSA/1 H CS version, on [U-15 N]-L-histidine·HCl·H2 O as a model sample under 70 kHz MAS. Then the 3D experiment is applied on glycyl-L-alanine at natural abundance, resulting in site-resolved 15 N CSA lineshapes from which CSA parameters are retrieved by SIMPSON numerical fittings. We demonstrate that this 3D R-symmetry-based pulse sequence is highly robust with respect to wide-range offset mismatches and weakly dependent to rf inhomogeneity within mis-sets of ±10% from the theoretical value.

Electrochemical Aflatoxin B1 immunosensor based on the use of graphene quantum dots and gold nanoparticles.

Electrochemical immunosensor for aflatoxin B1 (AFB1) is described that uses a composite prepared from graphene quantum dots (GQDs) and gold nanoparticles (Au NPs). The GQD-AuNP conjugate was obtained by using 2-aminothiophenol (ATP) as a linker where the carboxy groups of GQD bind to the amino groups of crosslinker via conjugation of thiol binding to the AuNP. To evaluate the conjugation of the GQD-AuNP composite, Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM) was applied. The composite was placed on an indium tin oxide (ITO) electrode and then modified with an antibody against AFB1. By using hexacyanoferrate as the electrochemical probe, the sensor works in the 0.1 to 3.0 ng mL-1 AFB1 concentration range, is highly specific, has good reproducibility and acceptable stability. The biosensor was applied to the analysis of (spiked) maize samples. Conceivably, the method can be utilized to sense other mycotoxins by using their respective antibodies. Graphical abstract Schematic presentation of electrochemical immunosensor for Aflatoxin B1 (AFB1) detection developed by antibodies of AFB1 (anti-AFB1) immobilization on graphene quantum dots (GQDs)-gold nanoparticles (AuNPs) composite deposited by electrophoretic deposition technique on an Indium tin oxide (ITO) surface.

Development of electrochemical biosensor based on CNT-Fe3O4 nanocomposite to determine formaldehyde adulteration in orange juice.

An electrochemical biosensor was developed to determine formaldehyde (HCHO) adulteration commonly found in food. The current responses of various electrodes based on multiwalled carbon nanotubes (CNTs) and synthesized nanocomposite (CNT-Fe3O4) were measured using cyclic voltammetry. The nanocomposite based biosensor shows comparatively high sensitivity (527 µA mg/L-1 cm-2), low detection limit (0.05 mg/L) in linear detection range 0.05-0.5 mg/L for formaldehyde detection using formaldehyde dehydrogenase (FDH) enzyme. In real sample analysis, the low obtained RSD values (less than 1.79) and good recovery rates (more than 90%) signify an efficient and precise sensor for the selective quantification of formaldehyde in orange juice. The developed biosensor has future implications for determining formaldehyde adulteration in citrus fruit juices and other liquid foods in agri-food chain to further resolve global food safety concerns, control unethical business practices of adulteration and reduce the widespread food borne illness outbreaks.

Detection of side-chain proton resonances of fully protonated biosolids in nano-litre volumes by magic angle spinning solid-state NMR.

We present a new solid-state NMR proton-detected three-dimensional experiment dedicated to the observation of protein proton side chain resonances in nano-liter volumes. The experiment takes advantage of very fast magic angle spinning and double quantum 13C-13C transfer to establish efficient (H)CCH correlations detected on side chain protons. Our approach is demonstrated on the HET-s prion domain in its functional amyloid fibrillar form, fully protonated, with a sample amount of less than 500 µg using a MAS frequency of 70 kHz. The majority of aliphatic and aromatic side chain protons (70%) are observable, in addition to Hα resonances, in a single experiment providing a complementary approach to the established proton-detected amide-based multidimensional solid-state NMR experiments for the study and resonance assignment of biosolid samples, in particular for aromatic side chain resonances.

A one-dimensional solid-state NMR approach for 14NH/14NH overtone correlation through 1H/1H mixing under fast MAS.

Homonuclear correlations are key to structural studies using solid-state NMR. In this contribution, using 14N overtone transition (OT) as a selective excitation approach, we propose a proton-detected one-dimensional (1D) 14NOT/14NOT/1H correlation solid-state NMR method mediated through 1H/1H mixing at fast magic angle spinning to achieve NH/NH proximities in naturally abundant samples. The proposed method is time efficient by a factor of ∼7.5 in comparison to the existing fundamental 14N frequency-based three-dimensional (3D) 14N/14N/1H correlation method.

Investigating the influence of charge transport on the performance of PTB7:PC71BM based organic solar cells.

A key challenge for researchers in the field of organic solar cells (OSCs) is to develop a physical model for a device that correctly describes the charge carrier transport phenomenon. In this article, an analytical study on the charge carrier transport phenomenon in an OSC is reported, which expresses a balance between free charge carrier generation and recombination in low mobility PTB7:PC71BM blend layers. First, the current density-voltage (J-V) data for the fabricated OSC were extracted from experiments by varying the incident power light intensity (IPL) and then analysis through theoretical simulation was used to quantify the dominant interface recombination parameters limiting the device's performance. It was found that although the generation of free charge carriers increased at higher IPL values, the performance of the device remained low due to poor electrical transport properties which resulted in a considerable accumulation of generated charge carriers in the active layer. Therefore, it has become important to work out the complex relation between charge carrier mobility, exciton-recombination dynamics and the overall electrical performance parameters in a single framework. This article explains the influence of incident power light intensity and charge carrier mobility on performance parameters, which limits the power conversion efficiency (PCE) of the OSC. The presented analysis could be helpful in optimizing the architecture of future devices to increase the PCE of OSCs.

Orbital tuberculosis with involvement of the eyelid: An unusual presentation.

Although cases of ocular tuberculosis (TB) are increasing, involvement of the eyelid and orbit are unusual. These cases occur secondary to the presence of TB elsewhere in the body, usually pulmonary TB. The primary infection of orbit or eyelid is a rare occurrence. We report a 4-year-old child with primary orbital TB and involvement of the eyelid. The diagnosis of TB should not be missed in patients with ocular symptoms (especially in India) as it is a treatable condition and delays in diagnosis or incorrect diagnosis can lead to serious sequelae.

Two-dimensional proton-detected (35)Cl/(1)H correlation solid-state NMR experiment under fast magic angle sample spinning: application to pharmaceutical compounds.

The determination of structure of hydrochloride salts of active pharmaceutical ingredients (HCl APIs) utilizing (35)Cl solid-state NMR studies has been of considerable interest in the recent past. Until now these studies relied on the (35)Cl direct observation method which has its own limitations in terms of the sensitivity and resolution due to the quadrupolar nature and the low gyromagnetic ratio of (35)Cl. In this contribution we demonstrate the two-dimensional (2D) (35)Cl/(1)H correlation measurement by using the proton detection-based (indirect observation of (35)Cl via(1)H) approach under fast magic angle sample spinning (MAS: 70 kHz). The main advantages of this approach over the direct observation method are highlighted in the present study. We have employed heteronuclear magnetization transfer through the recoupling of (35)Cl-(1)H heteronuclear dipolar interactions. The applicability of (35)Cl indirect detection method is first demonstrated on hydrochloride salts of amino acids, l-tyrosine·HCl and l-histidine·HCl·H2O following which the 2D (35)Cl/(1)H correlations are obtained for HCl APIs, procainamide HCl (Proc) and aminoguanidine HCl (Amin). On the basis of separation between the central transition (CT) and satellite transition (ST) peaks, and the shape/width of CT powder patterns, it is also shown that the quadrupolar parameters which are useful for the elucidation of the molecular structure can be determined. Moreover, the (35)Cl/(1)H correlations provide the precise determination of (1)H chemical shifts of nearby (35)Cl nuclei.

Sensitivity enhanced (14)N/(14)N correlations to probe inter-beta-sheet interactions using fast magic angle spinning solid-state NMR in biological solids.

(14)N/(14)N correlations are vital for structural studies of solid samples, especially those in which (15)N isotopic enrichment is challenging, time-consuming and expensive. Although (14)N nuclei have high isotopic abundance (99.6%), there are inherent difficulties in observing (14)N/(14)N correlations due to limited resolution and sensitivity related to: (i) low (14)N gyromagnetic ratio (γ), (ii) large (14)N quadrupolar couplings, (iii) integer (14)N spin quantum number (I = 1), and (iv) very weak (14)N-(14)N dipolar couplings. Previously, we demonstrated a proton-detected 3D (14)N/(14)N/(1)H correlation experiment at fast magic angle spinning (MAS) on l-histidine·HCl·H2O utilizing a through-bond (J) and residual dipolar-splitting (RDS) based heteronuclear multiple quantum correlation (J-HMQC) sequence mediated through (1)H/(1)H radio-frequency driven recoupling (RFDR). As an extension of our previous work, in this study we show the utility of dipolar-based HMQC (D-HMQC) in combination with (1)H/(1)H RFDR mixing to obtain sensitivity enhanced (14)N/(14)N correlations in more complex biological solids such as a glycyl-l-alanine (Gly-l-Ala) dipeptide, and parallel (P) and antiparallel (AP) ß-strand alanine tripeptides (P-(Ala)3 and AP-(Ala)3, respectively). These systems highlight the mandatory necessity of 3D (14)N/(14)N/(1)H measurements to get (14)N/(14)N correlations when the amide proton resonances are overlapped. Moreover, the application of long selective (14)N pulses, instead of short hard ones, is shown to improve the sensitivity. Globally, we demonstrate that replacing J-scalar with dipolar interaction and hard- with selective-(14)N pulses allows gaining a factor of ca. 360 in experimental time. On the basis of intermolecular NH/NH distances and (14)N quadrupolar tensor orientations, (14)N/(14)N correlations are effectively utilized to make a clear distinction between the parallel and antiparallel arrangements of the ß-strands in (Ala)3 through the observation of inter-ß-sheet correlations.

Proton-detected 3D (15)N/(1)H/(1)H isotropic/anisotropic/isotropic chemical shift correlation solid-state NMR at 70kHz MAS.

Chemical shift anisotropy (CSA) tensors offer a wealth of information for structural and dynamics studies of a variety of chemical and biological systems. In particular, CSA of amide protons can provide piercing insights into hydrogen-bonding interactions that vary with the backbone conformation of a protein and dynamics. However, the narrow span of amide proton resonances makes it very difficult to measure (1)H CSAs of proteins even by using the recently proposed 2D (1)H/(1)H anisotropic/isotropic chemical shift (CSA/CS) correlation technique. Such difficulties due to overlapping proton resonances can in general be overcome by utilizing the broad span of isotropic chemical shifts of low-gamma nuclei like (15)N. In this context, we demonstrate a proton-detected 3D (15)N/(1)H/(1)H CS/CSA/CS correlation experiment at fast MAS frequency (70kHz) to measure (1)H CSA values of unresolved amide protons of N-acetyl-(15)N-l-valyl-(15)N-l-leucine (NAVL).

Observation on dengue cases from a virus diagnostic laboratory of a tertiary care hospital in North India.

BACKGROUND & OBJECTIVES: The epidemiology of dengue fever (DF) is complex in the Indian subcontinent as all the four serotypes are circulating. This study reports observations on dengue cases from a virus diagnostic laboratory of a north Indian tertiary care hospital catering to areas in and around Lucknow, Uttar Pradesh. METHODS: Serum samples were obtained from suspected cases of dengue referred to the virus diagnostic laboratory during 2011 to 2013, and detailed history was taken on a pre-structured datasheet. All samples were tested for anti-dengue virus (DV) IgM antibodies and DV-non structural protein 1 antigen (NS1Ag) by ELISA. NS1Ag positive samples were tested further by conventional RT-PCR for DV-RNA detection and serotyping. RESULTS: Of the 4019 suspected patients of dengue, 886 (22%) showed laboratory evidence of dengue virus infection. Of these, 19, 17 and 27 per cent were positive in 2011, 2012 and 2013, respectively. Children and adults were similarly affected by dengue in all the three years. Males were more commonly affected than females. The predominant DV serotype detected was DV-2, DV-1 and DV-3 in 2011, 2012 and 2013, respectively. DV-4 serotype was not detected. About half the cases positive for DV infection, showed symptoms of dengue with warning signs/ severe dengue. A distinct seasonality with increase in number of dengue cases in the post monsoon period was seen. INTERPRETATION & CONCLUSIONS: Change in circulating serotype of dengue virus; a distinct adult dengue involvement; and a remarkable number of cases presenting with severe dengue manifestations are the main findings of this study.