Magnetic Resonance Spectroscopy Studies Research Articles

Brain N -acetyl-aspartyl-glutamate is associated with cognitive function in older virally suppressed people with HIV.

Cognitive impairment persists in virally suppressed people with HIV (VS-PWH) especially in higher order domains. One cortical circuit, linked to these domains, is regulated by N -acetyl-aspartyl glutamate (NAAG), the endogenous agonist of the metabotropic glutamate receptor 3. The enzyme glutamate carboxypeptidase II (GCPII) catabolizes NAAG and is upregulated in aging and disease. Inhibition of GCPII increases brain NAAG and improves learning and memory in rodent and primate models. As higher order cognitive impairment is present in VS-PWH, and NAAG has not been investigated in earlier magnetic resonance spectroscopy studies (MRS), we investigated if brain NAAG levels measured by MRS were associated with cognitive function. We conducted a retrospective analysis of 7-Tesla MRS data from a previously published study on cognition in older VS-PWH. The original study did not separately quantify NAAG, therefore, work for this report focused on relationships between regional NAAG levels in frontal white matter (FWM), left hippocampus, left basal ganglia and domain-specific cognitive performance in 40 VS-PWH after adjusting for confounds. Participants were older than 50 years, negative for affective and neurologic disorders, and had no prior 3-month psychoactive-substance use. Higher NAAG levels in FWM were associated with better attention/working memory. Higher left basal ganglia NAAG related to better verbal fluency. There was a positive relationship between hippocampal NAAG and executive function which lost significance after correction for confounds. These data suggest brain NAAG serves as a biomarker of cognition in VS-PWH. Pharmacological modulation of brain NAAG warrants investigation as a therapeutic approach for cognitive deficits in VS-PWH.

Reduced Thalamic Gamma Aminobutyric Acid (GABA) in Painless but not Painful Diabetic Peripheral Neuropathy.

Alterations in the structure, function, and microcirculation of the thalamus, a key brain region involved in pain pathways, have previously been demonstrated in patients with Painless- and Painful-diabetic peripheral neuropathy (DPN). However, thalamic neurotransmitter levels including GABA (inhibitory neurotransmitter) and glutamate (excitatory neurotransmitter) in different DPN phenotypes are not known. We performed a Magnetic Resonance Spectroscopy study and quantified GABA and glutamate levels within the thalamus, in a carefully characterised cohort of participants with Painless- and Painful-DPN. Participants with DPN (Painful- and Painless combined) had a significantly lower GABA:H2O ratio compared to those without DPN (Healthy volunteers [HV] and diabetes without DPN [No-DPN]). Participants with Painless-DPN had the lowest GABA:H2O ratio, which reached significance compared with HV and No-DPN, but not Painful-DPN. There was no difference in GABA:H2O in Painful-DPN compared with all other groups. A significant correlation with GABA:H2O and neuropathy severity was also seen. This study demonstrates that lower levels of thalamic GABA in participants with Painless-DPN may reflect neuroplasticity due to reduced afferent pain impulses. Whereas partially preserved levels of GABA in Painful-DPN may indicate that central GABAergic pathways are involved in the mechanisms of neuropathic pain in diabetes.

Micro- and Nano-Pollutants from Tires and Car Brakes Generated in the Winter Season in the Poznan City Urban Environment

This research, focusing on the environmental impact of tire and brake disc pad wear, constitutes a significant area of transport-related studies. These two key vehicle components are not only the most frequently worn but also generate micro- and nano-pollutants (i.e., rubber, metal oxides) that potentially harm the environment. Over half of the globally produced natural and synthetic rubbers, which amounted to about 30 million tons in 2022, are used for tire production. This work focuses on the study of roadside snow, sand, and standing water deposits from various locations in the urban agglomeration (Poznań, Poland) during the winter season, determining their qualitative composition and the quantitative content of pollutants originating from tire abrasion. In addition, the method of washing nano- and micro-rubber particles and their full characteristics was also presented. Fourier-transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopic studies, optical and scanning electron microscopy (SEM-EDS), particle size studies using a dynamic light scattering (DLS) particle analyzer, and thermogravimetric analysis (TGA) were conducted for a detailed characterization of the pollutants in the environment. The conducted particle separation methods allowed for the extraction of a fraction mainly containing gum residues with particle sizes less than 2 µm. The results of these tests make it possible to estimate the level of contamination with rubber and metal residues during the abrasion of tires, pads, and brake discs while driving, which is crucial for understanding the impact of vehicle part exploitation on the environment.

Glutamate imbalance in key structure of the default mode network in adults with attention-deficit/hyperactivity disorder.

The default mode network (DMN) is atypically active in patients with ADHD, likely contributing to the inattention patterns observed in patients with the disorder. Nonetheless, magnetic resonance spectroscopy (MRS) studies have rarely targeted the posterior cingulate cortex, a key DMN region, and little is known about the biochemical setting within this network in patients with ADHD. We aimed to assess the differences in metabolite profiles of the posterior cingulate cortex-a key region of the DMN-between patients with ADHD and controls. Five brain metabolites-glutamate, inositol, N-acetyl aspartate, choline, and creatine-were measured through MRS in the posterior cingulate cortex of patients and controls in a 3.0T scanner. Between-group comparison of neurometabolite concentrations in PCC was performed using multivariate analysis of covariance. A total of 88 patients and 44 controls were included in the analysis. Patients with ADHD showed lower levels of glutamate in the posterior cingulate cortex compared to controls (p = 0.003). Lower concentrations of glutamate in the posterior cingulate cortex suggest that a glutamatergic imbalance within the posterior cingulate cortex might play a role in the pathogenesis of ADHD. Further understanding of the causes and consequences of such glutamate decrease might help explain how some glutamate-related drug effects impact on ADHD symptomatology.

Preliminary study of proton magnetic resonance spectroscopy to assess bone marrow adiposity in the third metacarpus or metatarsus in Thoroughbred racehorses.

Magnetic resonance spectroscopy (MRS) has been used to investigate metabolic changes within human bone. It may be possible to use MRS to investigate bone metabolism and fracture risk in the distal third metacarpal/tarsal bone (MC/MTIII) in racehorses. To determine the feasibility of using MRS as a quantitative imaging technique in equine bone by using the 1H spectra for the MC/MTIII to calculate fat content (FC). Observational cross-sectional study. Limbs from Thoroughbred racehorses were collected from horses that died or were subjected to euthanasia on racecourses. Each limb underwent magnetic resonance imaging (MRI) at 3 T followed by single-voxel MRS at three regions of interest (ROI) within MC/MTIII (lateral condyle, medial condyle, proximal bone marrow [PBM]). Percentage FC was calculated at each ROI. Each limb underwent computed tomography (CT) and bone mineral density (BMD) was calculated for the same ROIs. All MR and CT images were graded for sclerosis. Histology slides were graded for sclerosis and proximal marrow space was calculated. Pearson or Spearman correlations were used to assess the relationship between BMD, FC and marrow space. Kruskal-Wallis tests were used to check for differences between sclerosis groups for BMD or FC. Eighteen limbs from 10 horses were included. A negative correlation was identified for mean BMD and FC for the lateral condyle (correlation coefficient = -0.60, p = 0.01) and PBM (correlation coefficient = -0.5, p = 0.04). There was a significant difference between median BMD for different sclerosis grades in the condyles on both MRI and CT. A significant difference in FC was identified between sclerosis groups in the lateral condyle on MRI and CT. Small sample size. 1H Proton MRS is feasible in the equine MC/MTIII. Further work is required to evaluate the use of this technique to predict fracture risk in racehorses.

Elevated circulating soluble interleukin-2 receptor (sCD25) level is associated with prefrontal excitatory-inhibitory imbalance in individuals with chronic pain: A proton MRS study

Aberrant neuronal excitability in the anterior cingulate cortex (ACC) is implicated in cognitive and affective pain processing. Such excitability may be amplified by activated circulating immune cells, including T lymphocytes, that interact with the central nervous system. Here, we conducted a study of individuals with chronic pain using magnetic resonance spectroscopy (MRS) to investigate the clinical evidence for the interaction between peripheral immune activation and prefrontal excitatory-inhibitory imbalance. In thirty individuals with chronic musculoskeletal pain, we assessed markers of peripheral immune activation, including soluble interleukin-2 receptor alpha chain (sCD25) levels, as well as brain metabolites, including Glx (glutamate + glutamine) to GABA+ (γ-aminobutyric acid + macromolecules/homocarnosine) ratio in the ACC. We found that the circulating level of sCD25 was associated with prefrontal Glx/GABA+. Greater prefrontal Glx/GABA+ was associated with higher pain catastrophizing, evaluative pain ratings, and anxiodepressive symptoms. Further, the interaction effect of sCD25 and prefrontal Glx/GABA+ on pain catastrophizing was significant, indicating the joint association of these two markers with pain catastrophizing. Our results provide the first evidence suggesting that peripheral T cellular activation, as reflected by elevated circulating sCD25 levels, may be linked to prefrontal excitatory-inhibitory imbalance in individuals with chronic pain. The interaction between these two systems may play a role as a potential mechanism underlying pain catastrophizing. Further prospective and treatment studies are needed to elucidate the specific role of the immune and brain interaction in pain catastrophizing.

NMR Spectroscopy in Diagnosis and Monitoring of Methylmalonic and Propionic Acidemias.

Although both localized nuclear magnetic resonance spectroscopy (MRS) and non-localized nuclear magnetic resonance spectroscopy (NMR) generate the same information, i.e., spectra generated by various groups from the structure of metabolites, they are rarely employed in the same study or by the same research group. As our review reveals, these techniques have never been applied in the same study of methylmalonic acidemia (MMA), propionic acidemia (PA) or vitamin B12 deficiency patients. On the other hand, MRS and NMR provide complementary information which is very valuable in the assessment of the severity of disease and efficiency of its treatment. Thus, MRS provides intracellular metabolic information from localized regions of the brain, while NMR provides extracellular metabolic information from biological fluids like urine, blood or cerebrospinal fluid. This paper presents an up-to-date review of the NMR and MRS studies reported to date for methylmalonic and propionic acidemias. Vitamin B12 deficiency, although in most of its cases not inherited, shares similarities in its metabolic effects with MMA and it is also covered in this review.

Peak Resembling N-acetylaspartate (NAA) on Magnetic Resonance Spectroscopy of Brain Metastases.

Background and Objectives: Differentiating between a high-grade glioma (HGG) and solitary cerebral metastasis presents a challenge when using standard magnetic resonance imaging (MRI) alone. Magnetic resonance spectroscopy (MRS), an advanced MRI technique, may assist in resolving this diagnostic dilemma. N-acetylaspartate (NAA), an amino acid found uniquely in the central nervous system and in high concentrations in neurons, typically suggests HGG over metastatic lesions in spectra from ring-enhancing lesions. This study investigates exceptions to this norm. Materials and Methods: We conducted an MRS study on 49 histologically confirmed and previously untreated patients with brain metastases, employing single-voxel (SVS) techniques with short and long echo times, as well as magnetic resonance spectroscopic imaging (MRSI). Results: In our cohort, 44 out of 49 (90%) patients demonstrated a typical MR spectroscopic profile consistent with secondary deposits: a Cho peak, very low or absent Cr, absence of NAA, and the presence of lipids. A peak at approximately 2 ppm, termed the "NAA-like peak", was present in spectra obtained with both short and long echo times. Among the MRS data from 49 individuals, we observed a peak at 2.0 ppm in five brain metastases from mucinous carcinoma of the breast, mucinous non-small-cell lung adenocarcinoma, two metastatic melanomas, and one metastatic non-small-cell lung cancer. Pathohistological verification of mucin in two of these five cases suggested this peak likely represents N-acetyl glycoproteins, indicative of mucin expression in cancer cells. Conclusions: The identification of a prominent peak at 2.0 ppm could be a valuable diagnostic marker for distinguishing single ring-enhancing lesions, potentially associated with mucin-expressing metastases, offering a new avenue for diagnostic specificity in challenging cases.

Metabolic fingerprinting by nuclear magnetic resonance of hepatocellular carcinoma cells during p53 reactivation-induced senescence.

Cellular senescence is characterized by stable cell cycle arrest. Senescent cells exhibit a senescence-associated secretory phenotype that can promote tumor progression. The aim of our study was to identify specific nuclear magnetic resonance (NMR) spectroscopy-based markers of cancer cell senescence. For metabolic studies, we employed murine liver carcinoma Harvey Rat Sarcoma Virus (H-Ras) cells, in which reactivation of p53 expression induces senescence. Senescent and nonsenescent cell extracts were subjected to high-resolution proton (1H)-NMR spectroscopy-based metabolomics, and dynamic metabolic changes during senescence were analyzed using a magnetic resonance spectroscopy (MRS)-compatible cell perfusion system. Additionally, the ability of intact senescent cells to degrade the extracellular matrix (ECM) was quantified in the cell perfusion system. Analysis of senescent H-Ras cell extracts revealed elevated sn-glycero-3-phosphocholine, myoinositol, taurine, and creatine levels, with decreases in glycine, o-phosphocholine, threonine, and valine. These metabolic findings were accompanied by a greater degradation index of the ECM in senescent H-Ras cells than in control H-Ras cells. MRS studies with the cell perfusion system revealed elevated creatine levels in senescent cells on Day 4, confirming the 1H-NMR results. These senescence-associated changes in metabolism and ECM degradation strongly impact growth and redox metabolism and reveal potential MRS signals for detecting senescent cancer cells in vivo.

Biophysical characterization and design of a minimal version of the Hoechst RNA aptamer

RNA aptamers are oligonucleotides, selected through Systematic Evolution of Ligands by EXponential Enrichment (SELEX), that can bind to specific target molecules with high affinity. One such molecule is the RNA aptamer that binds to a blue-fluorescent Hoechst dye that was modified with bulky t-Bu groups to prevent non-specific binding to DNA. This aptamer has potential for biosensor applications; however, limited information is available regarding its conformation, molecular interactions with the ligand, and binding mechanism. The study presented here aims to biophysically characterize the Hoechst RNA aptamer when complexed with the t-Bu Hoechst dye and to further optimize the RNA sequence by designing and synthesizing new sequence variants. Each variant aptamer-t-Bu Hoechst complex was evaluated through a combination of fluorescence emission, native polyacrylamide gel electrophoresis, fluorescence titration, and isothermal titration calorimetry experiments. The results were used to design a minimal version of the aptamer consisting of only 21 nucleotides. The performed study also describes a more efficient method for synthesizing the t-Bu Hoechst dye derivative. Understanding the biophysical properties of the t-Bu Hoechst dye-RNA complex lays the foundation for nuclear magnetic resonance spectroscopy studies and its potential development as a building block for an aptamer-based biosensor that can be used in medical, environmental or laboratory settings.

GABA and Glx predict EEG responses of visual sensitivity in autism.

The mechanisms underlying atypical sensory processing in autism remain to be elucidated, but research points toward a role of the glutamatergic/GABAergic balance. To investigate the potential relationships between visual sensitivity and its molecular correlates in autism, we combined data from electroencephalography (EEG) and magnetic resonance spectroscopy (MRS) studies. Twenty autistic adults and sixteen neurotypical adults (NT) participated in both an EEG study assessing visual sensitivity (Sapey-Triomphe et al., Autism Research, 2023) and in an MRS study measuring Glx and GABA+ concentrations in the occipital cortex (Sapey-Triomphe et al., Molecular Autism, 2021). These studies revealed no group differences in neural detection thresholds or in Glx/GABA levels in the occipital cortex. Neural detection thresholds for contrast and spatial frequency (SF) were determined using fast periodic visual stimulations and neural frequency tagging. In the present study, Glx/GABA+ concentrations in the occipital cortex and neural detection thresholds did not differ between groups. Interestingly, lower Glx/GABA+ ratios were associated with lower contrast detection thresholds and higher SF detection thresholds. These correlations were also significant within the neurotypical and autistic groups. This report suggests that the Glx/GABA balance regulates visual detection thresholds across individuals. In both autistic and NTs, lower Glx/GABA ratios in the occipital cortex allow for better detection of visual inputs at the neural level. This study sheds light on the neurochemical underpinnings of visual sensitivity in autism and warrants further investigation.

GABA in the anterior cingulate cortex mediates the association of white matter hyperintensities with executive function: a magnetic resonance spectroscopy study.

White matter hyperintensities (WMH) and gamma-aminobutyric acid (GABA) are associated with executive function. Multiple studies suggested cortical alterations mediate WMH-related cognitive decline. The aim of this study was to investigate the crucial role of cortical GABA in the WMH patients. In the 87 WMH patients (46 mild and 41 moderate to severe) examined in this study, GABA levels in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) assessed by the Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence, WMH volume and executive function were compared between the two groups. Partial correlation and mediation analyses were carried out to examine the GABA levels in mediating the association between WMH volume and executive function. Patients with moderate to severe WMH had lower GABA+/Cr in the ACC (p = 0.034) and worse executive function (p = 0.004) than mild WMH patients. In all WMH cases, the GABA+/Cr levels in the ACC mediated the negative correlation between WMH and executive function (ab: effect = -0.020, BootSE = 0.010, 95% CI: -0.042 to -0.004). This finding suggested GABA+/Cr levels in the ACC might serve as a protective factor or potential target for preventing the occurrence and progression of executive function decline in WMH people.

Biophysical and nuclear magnetic resonance spectroscopic studies of the binding of baicalein to DNA sequence d(CACGTG)2 and its cytotoxicity evaluation

This paper reports the interaction of baicalein with a hexamer nucleic acid sequence d(CACGTG)2, present in the promoter region of various transcription factors, using biophysical techniques and nuclear magnetic resonance spectroscopy. UV–Visible absorption and fluorescence titration data implied partial intercalative binding of baicalein with a binding constant of 105 M−1. Continuous variation analysis using fluorescence data revealed a 1:1 stoichiometry of the baicalein and DNA in the solution. Circular dichroism data displayed a structural change of DNA upon baicalein binding. Thermal denaturing studied using circular dichroism showed that the melting temperature of the system does not significantly vary with the addition of baicalein. The spectral features suggest a partial intercalation of baicalein. Differential scanning calorimetric data exhibited two two-state transitions for alone DNA and its 1:1 complex with subtle changes in the melting temperatures supporting the non-intercalative binding of baicalein. Nuclear magnetic resonance data showed baicalein binding to the region near the C3pG4 base step, evidenced by the intermolecular nuclear overhauser effect cross peaks. Distance restrained molecular dynamics was employed to obtain the lowest energy structure. Biological evaluation of the effect of baicalein displayed excellent apoptotic effect on different cancer cell lines. IC50 values of 72.55, 79.9 and 96.7 µM were obtained in MCF-7, DU-145 and HCT-15 cell lines. The results uphold its chemotherapeutic potential.

Association of Age and Response to Methylphenidate HCL Treatment in Adult ADHD: A Proton Magnetic Resonance Spectroscopy Study.

This study investigated the age-dependent effects of methylphenidate (MPH) on brain metabolites including choline (Cho), N-acetyl aspartate (NAA) and creatine (Cr) levels in the dorsolateral prefrontal cortex (DLPFC), striatum, cerebellum, and anterior cingulate cortex (ACC) regions of the brain in adult patients with attention deficit hyperactivity disorder (ADHD). The study was included 60 patients with ADHD between the ages of 18 and 60 years. The patients were grouped with respect to their ages as follows: 18-24 years, 25-30 years, and 31 and over years. Levels of NAA, Cr and Cho in DLPFC, ACC, cerebellum and striatum were measured with magnetic resonance spectroscopy (MRS). Subjects were then given 10 mg of oral MPH and the same metabolite levels were measured 30 minutes apart. Twelve (20%) of the cases were female and 48 (80%) were male. The age distribution of the cases is as follows: 15 subjects between the ages of 18-24, 26 subjects between the ages of 25-30 and 19 subjects over the age of 30. NAA levels were higher after MPH in the DLPFC of the 18-24 age group (p = 0.016) and in the cerebellum of the 25-30 age group (p = 0.041). No increase in Cho and Cr levels was observed after treatment compared to before (p > 0.05). It is thought that treatment of MPH can be effective on metabolites in different brain regions and this effect can vary upon age adult ADHD patients. After MPH treatment, both the 18-24 age group (in the DLPFC) and the 25-30 age group (in the cerebellum) was detected significantly higher NAA levels compared to pre-treatment levels. This increase in NAA levels suggested that pharmacotherapy, especially at early ages, may be effective on neuronal damage.

Neurochemical differences in core regions of the autistic brain: a multivoxel 1H-MRS study in children

Autism spectrum disorder (ASD) is a neurodevelopmental condition which compromises various cognitive and behavioural domains. The understanding of the pathophysiology and molecular neurobiology of ASD is still an open critical research question. Here, we aimed to address ASD neurochemistry in the same time point at key regions that have been associated with its pathophysiology: the insula, hippocampus, putamen and thalamus. We conducted a multivoxel proton magnetic resonance spectroscopy (1H-MRS) study to non-invasively estimate the concentrations of total choline (GPC + PCh, tCho), total N-acetyl-aspartate (NAA + NAAG, tNAA) and Glx (Glu + Gln), presenting the results as ratios to total creatine while investigating replication for ratios to total choline as a secondary analysis. Twenty-two male children aged between 10 and 18 years diagnosed with ASD (none with intellectual disability, in spite of the expected lower IQ) and 22 age- and gender-matched typically developing (TD) controls were included. Aspartate ratios were significantly lower in the insula (tNAA/tCr: p = 0.010; tNAA/tCho: p = 0.012) and putamen (tNAA/tCr: p = 0.015) of ASD individuals in comparison with TD controls. The Glx ratios were significantly higher in the hippocampus of the ASD group (Glx/tCr: p = 0.027; Glx/tCho: p = 0.011). Differences in tNAA and Glx indices suggest that these metabolites might be neurochemical markers of region-specific atypical metabolism in ASD children, with a potential contribution for future advances in clinical monitoring and treatment.

Central nervous system involvement in chronic inflammatory demyelinating polyradiculoneuropathy—MRS and DTI study

ObjectiveThe current research aimed to analyze the alterations within the motor cortex and pyramidal pathways and their association with the degree of damage within the peripheral nerve fibers in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). To achieve that goal, we investigated the microstructural changes within the pyramidal white matter tracts using diffusion tensor imaging (DTI) parameters, evaluated metabolic alterations in both precentral gyri using magnetic resonance spectroscopy (MRS) ratios, and correlated them with the neurographic findings in patients with CIDP.MethodsThe spectroscopic ratios of NAA/Cr, Cho/Cr, and mI/Cr from both precentral gyri and the values of fractional anisotropy (FA), axial diffusivity (AD), and mean diffusivity (MD) from both of the corticospinal tracts were correlated with the results of neurological and neurographic findings. The comparison of DTI parameters between the patients and controls was performed using Student’s t-test or the Mann–Whitney U test. Due to the lack of normal distribution of most variables, Spearman’s Rho rank coefficient was used to test all correlations. All analyses were performed at a significant level of alpha = 0.05 using STATISTICA 13.3.ResultsCompared to the control group (CG), the patient group showed significantly lower ratios of NAA/Cr (1.66 ± 0.11 vs. 1.61 ± 0.15; p = 0.022), higher ratios of ml/Cr in the right precentral gyrus (0.57 ± 0.15 vs. 0.61 ± 0.08; p = 0.005), and higher levels of Cho/Cr within the left precentral gyrus (0.83 ± 0.09 vs. 0.88 ± 0.14, p = 0.012). The DTI parameters of MD from the right CST and AD from the right and left CSTs showed a strong positive correlation (0.52–0.53) with the sural sensory nerve action potential (SNAP) latency of the right sural nerve. There were no other significant correlations between other DTI and MRS parameters and neurographic results.SignificanceIn our study, significant metabolic alterations were found in the precentral gyri in patients with CIDP without clinical symptoms of central nervous system involvement. The revealed changes reflected neuronal loss or dysfunction, myelin degradation, and increased gliosis. Our results suggest coexisting CNS damage in these patients and may provide a new insight into the still unknown pathomechanism of CIDP.

A stable rhodium-coordinated carbene with a σ0π2 electronic configuration.

Isolable singlet carbenes have universally adopted a σ2π0 electronic state, making them σ-donors and π-acceptors. We present a rhodium-coordinated, cationic cyclic diphosphinocarbene with a σ0π2 ground state configuration. Nuclear magnetic resonance spectroscopy studies show a carbene carbon chemical shift below -30.0 parts per million. X-ray crystallography reveals a planar RhP2C configuration. Quantum chemical calculations rationalize how σ-electron delocalization/donation and π-electron negative hyperconjugation together stabilize the formally vacant σ orbital and the filled π orbital at the carbene center. In contrast to traditional carbene counterparts this carbene can undergo synthetic transformations with both a Lewis base and a silver salt, producing a Lewis acid/base adduct and a silver π-complex, respectively. Exhibiting ambiphilic reactivity, it can also form a ketenimine through reaction with an isocyanide.

Resting state and activated brain glutamate-glutamine, brain lactate, cognition, and psychopathology among males with schizophrenia: A 3 Tesla proton magnetic resonance spectroscopic (1H-MRS) study.

Research on glutamate (Glu) in schizophrenia has so far been inconclusive. Based on preclinical studies on Glu lactate interaction, researchers have now focused on brain lactate level as a sign of major pathology, including cognitive dysfunctions in the brain. Our study aimed to examine changes at resting and activated states in brain lactate and Glu-glutamine (Glx) at the anterior cingulate cortex (ACC) in schizophrenia. A hospital-based prospective study was conducted with twenty-two male cases of schizophrenia and matched healthy controls (HCs). Positive and Negative Syndrome Scale (PANSS), Montreal Cognitive Assessment (MoCA), and Stroop tasks were administered among patients. Brain lactate and Glx at ACC were measured at resting state and during the Stroop test with proton magnetic resonance spectroscopy (1H-MRS) both at baseline and at remission and once among HC. Though MoCA scores improved significantly (P < 0.001) at remission from baseline among cases, repeated-measures analysis of variance (RM-ANOVA) did not find a significant time effect for Glx (P = 0.82) and lactate (P = 0.30) among cases from baseline to remission. Glx and lactate changed differently from baseline to remission. Our study did not find significant differences in Glx and lactate between schizophrenia patients and HC. No significant time effect on Glx and lactate was observed from baseline to remission among schizophrenia cases. Different changes observed in Glx and lactate from baseline to remission require replication in future studies with larger sample size, longer follow-up period, and multivoxel MR assessment.

Citric acid cross-linking of a hydrogel from Aloe vera (Aloe barbadensis M.) engenders a pH-responsive, superporous, and smart material for drug delivery.

The current research work is based on the evaluation of a citric acid (CA) cross-linked Aloe vera (Aloe barbadensis M.) leaf hydrogel (CL-ALH) for pH-dependent and sustained drug release application. The CA was used in different concentrations (1.25, 2.5, 5.0, and 10.0%) to cross-link the ALH using homogenous reaction conditions. The synthesis of CL-ALH was confirmed through Fourier transform and nuclear magnetic resonance spectroscopic studies. The thermal analysis indicated that the ALH and CL-ALH were stable and decomposed in two steps. The scanning electron microscopic images of CL-ALH confirmed its porous nature due to the presence of interconnected channeling. The swelling of CL-ALH was evaluated at pH 1.2, 6.8, and 7.4 as well as in deionized water (DW). High swelling of CL-ALH was observed in DW, and at pH 7.4 and 6.8 whereas, less swelling of CL-ALH was witnessed at pH 1.2. CL-ALH also exhibited swelling/deswelling behavior in DW and ethanol, DW and normal saline, and at pH 7.4 and 1.2. Tablets were prepared from CL-ALH as a release retarding agent demonstrating the sustained release of venlafaxine hydrochloride (VFX) for 8 h. Whereas, VFX was released within 4 h from the ALH-based tablet formulation (un-cross-linked material) indicating the prolonged and sustained release behavior of CL-ALH. The VFX was released from CL-ALH tablets and followed zero-order kinetics. The mechanism followed by VFX release from CL-ALH tablets was non-Fickian diffusion. The in vivo fate of the tablet formulation was observed through an X-ray study. The CL-ALH-based tablet safely passed through the stomach of a stray dog without any significant erosion and then disintegrated in the small intestine and colon. These findings confirmed that the CL-ALH is an effective excipient for designing a sustained-release drug delivery system for the small intestine and colon.

(Invited) Advances in Photon-Harvesting Technologies for Perovskite Absorbers and Water Splitting Reactions

Hybrid halide perovskites have made significant progress in power conversion efficiencies (> 25 %) and high stability achieved through chemical engineering of the AMX3 composition. Compositional engineering of perovskite precursor inks minimizes batch-to-batch variations and fluctuation in PCE values, however the understanding of perovskite inks and solution behavior remains a key step towards the exploitation of solution-processed perovskite devices. Herein, a comprehensive 207Pb nuclear magnetic resonance spectroscopy (NMR) study performed on various lead perovskite precursor inks will be presented. The NMR data provide fresh insights in identifying molecular species that are invariably and predominantly formed in precursor mixtures to coexist with larger networks and colloids. The solution chemistry of PbI2+I- is dominated by the type of connectivity as edge- face- and corner-sharing (PbI6)-octahedra and their dimensionality. The trends in the 207Pb chemical shifts revealed dynamic equilibria in the inks that can be controlled by stoichiometry, nature of the solvents and temperature. Furthermore, perovskite precursor ink development can be applied to fabricate devices beyond the planar device structures, such as direct electrospinning of the three major perovskite solar cell components, namely, photo absorber, hole, and electron transport materials, as continuous single triaxial fibers of μm radial dimensions. These perovskite fibers lay the foundation of materials engineering for fabricating tiny solar cells, which can either be woven into fabrics or incorporated as single fibers to power wearables and a variety of devices or sensors, forming the internet of things. They are also suited for tandem PV-PEC set-up for solar-assisted photoelectrochemical production of hydrogen by water-splitting reactions.