Delayed cerebrovascular reactivity in individuals with spinal cord injury in the right inferior parietal lobe: a breath-hold functional near-infrared spectroscopy study.

Cerebrovascular reactivity (CVR) reflects the ability of blood vessels to dilate or constrict in response to a vasoactive stimulus, and allows researchers to assess the brain's vascular health. Individuals with spinal cord injury (SCI) are at an increased risk for autonomic dysfunction in addition to cognitive impairments, which have been linked to a decline in CVR; however, there is currently a lack of brain-imaging studies that investigate how CVR is altered after SCI. In this study, we used a breath-holding hypercapnic stimulus and functional near-infrared spectroscopy (fNIRS) to investigate CVR alterations in individuals with SCI (n = 20, 14M, 6F, mean age = 46.3 ± 10.2 years) as compared to age- and sex-matched able-bodied (AB) controls (n = 25, 19M, 6F, mean age = 43.2 ± 12.28 years). CVR was evaluated by its amplitude and delay components separately by using principal component analysis and cross-correlation analysis, respectively. We observed significantly delayed CVR in the right inferior parietal lobe in individuals with SCI compared to AB controls (linear mixed-effects model, fixed-effects estimate = 6.565, Satterthwaite's t-test, t = 2.663, p = 0.008), while the amplitude of CVR was not significantly different. The average CVR delay in the SCI group in the right inferior parietal lobe was 14.21 s (sd: 6.60 s), and for the AB group, the average delay in the right inferior parietal lobe was 7.08 s (sd: 7.39 s). CVR delays were also associated with the duration since injury in individuals with SCI, in which a longer duration since injury was associated with a shortened delay in CVR in the right inferior parietal region (Pearson's r-correlation, r = -0.59, p = 0.04). This study shows that fNIRS can be used to quantify changes in CVR in individuals with SCI, and may be further used in rehabilitative settings to monitor the cerebrovascular health of individuals with SCI.

Anti-respiratory syncytial virus and anti-herpes simplex virus activity of chemically engineered sulfated fucans from Cystoseira indica.

Seaweed polysaccharides, particularly sulfated ones, exhibited potent antiviral activity against a wide variety of enveloped viruses, such as herpes simplex virus and respiratory viruses. Different mechanisms of action were suggested, which may range from preventing infection to intracellular antiviral activity, at different stages of the viral cycle. Herein, we generated two chemically engineered sulfated fucans (C303 and C304) from Cystoseira indica by an amalgamated extraction-sulfation procedure using chlorosulfonic acid-pyridine/N,N-dimethylformamide and sulfur trioxide-pyridine/N,N-dimethylformamide reagents, respectively. These compounds exhibited activity against HSV-1 and RSV with 50 % inhibitory concentration values in the range of 0.75-2.5 µg/mL and low cytotoxicity at concentrations up to 500 µg/mL. The antiviral activities of chemically sulfated fucans (C303 and C304) were higher than the water (C301) and CaCl2 extracted (C302) polysaccharides. Compound C303 had a (1,3)-linked fucan backbone and was branched. Sulfates were present at positions C-2, C-4, and C-2,4 of Fucp, and C-6 of Galp residues of this polymer. Compound C304 had a comparable structure but with more sulfates at C-4 of Fucp residue. Both C303 and C304 were potent antiviral candidates, acting in a dose-dependent manner on the adsorption and other intracellular stages of HSV-1 and RSV replication, in vitro.

Brain activation during the N-back working memory task in individuals with spinal cord injury: a functional near-infrared spectroscopy study.

Cognitive impairments have frequently been reported in individuals with spinal cord injury (SCI) across different domains such as working memory, attention, and executive function. The mechanism of cognitive impairment after SCI is not well understood due to the heterogeneity of SCI sample populations, and may possibly be due to factors such as cardiovascular dysfunction, concomitant traumatic brain injury (TBI), hypoxia, sleep disorders, and body temperature dysregulation. In this study, we implement the Neuropsychiatric Unit Cognitive Assessment Tool (NUCOG) to assess cognitive differences between individuals with SCI and age-matched able-bodied (AB) controls. We then use an N-back working memory task and functional near-infrared spectroscopy (fNIRS) to elucidate the neurovascular correlates of cognitive function in individuals with SCI. We observed significant differences between the SCI and AB groups on measures of executive function on the NUCOG test. On the N-back task, across the three levels of difficulty: 0-back, 2-back, and 3-back, no significant differences were observed between the SCI and AB group; however, both groups performed worse as the level of difficulty increased. Although there were no significant differences in N-back performance scores between the two groups, functional brain hemodynamic activity differences were observed between the SCI and AB groups, with the SCI group exhibiting higher maximum oxygenated hemoglobin concentration in the right inferior parietal lobe. These findings support the use of fNIRS to study cognitive function in individuals with SCI and may provide a useful tool during rehabilitation to obtain quantitative functional brain activity metrics.

Synchronous Proton-Hydride Transfer by a Pyrazole-Functionalized Protic Mn(I) Complex in Catalytic Alcohol Dehydrogenative Coupling.

A series of Mn(I) complexes Mn(L1 )(CO)3 Br, Mn(L2 )(CO)3 Br, Mn(L1 )(CO)3 (OAc) and Mn(L3 )(CO)3 Br [L1 =2-(5-tert-butyl-1H-pyrazol-3-yl)-1,8-naphthyridine, L2 =2-(5-tert-butyl-1H-pyrazol-3-yl)pyridine, L3 =2-(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)-1,8-naphthyridine] were synthesized and fully characterized. The acid-base equilibrium between the pyrazole and the pyrazolato forms of Mn(L1 )(CO)3 Br was studied by 1 H NMR and UV-vis spectra. These complexes are screened as catalysts for acceptorless dehydrogenative coupling (ADC) of primary alcohols and aromatic diamines for the synthesis of benzimidazole and quinoline derivatives with the release of H2 and H2 O as byproducts. The protic complex Mn(L1 )(CO)3 Br shows the highest catalytic activity for the synthesis of 2-substituted benzimidazole derivatives with broad substrate scope, whereas a related complex [Mn(L3 )(CO)3 Br], which is devoid of the proton responsive ß-NH unit, shows significantly reduced catalytic efficiency validating the crucial role of the ß-NH functionality for the alcohol dehydrogenation reactions. Control experiments, kinetic and deuterated studies, and density functional theory (DFT) calculations reveal a synchronous hydride-proton transfer by the metal-ligand construct in the alcohol dehydrogenation step.

Comparative treatment costs of risk-stratified therapy for childhood acute lymphoblastic leukemia in India.

BACKGROUND: To evaluate the treatment cost and cost effectiveness of a risk-stratified therapy to treat pediatric acute lymphoblastic leukemia (ALL) in India. METHODS: The cost of total treatment duration was calculated for a retrospective cohort of ALL children treated at a tertiary care facility. Children were risk stratified into standard (SR), intermediate (IR) and high (HR) for B-cell precursor ALL, and T-ALL. Cost of therapy was obtained from the hospital electronic billing systems and details of outpatient (OP) and inpatient (IP) from electronic medical records. Cost effectiveness was calculated in disability-adjusted life years. RESULTS: One hundred and forty five patients, SR (50), IR (36), HR (39), and T-ALL (20) were analyzed. Median cost of the entire treatment for SR, IR, HR, and T-ALL was found to be $3900, $5500, $7400, and $8700, respectively, with chemotherapy contributing to 25%-35% of total cost. Out-patient costs were significantly lower for SR (p < 0.0001). OP costs were higher than in-patient costs for SR and IR, while in-patient costs were higher in T-ALL. Costs for non-therapy admissions were significantly higher in HR and T-ALL (p < 0.0001), representing over 50% of costs of in-patient therapy. HR and T-ALL also had longer durations of non-therapy admissions. Based on WHO-CHOICE guidelines, the risk-stratified approach was very cost effective for all categories of patients. CONCLUSIONS: Risk-stratified approach to treat childhood ALL is very cost-effective for all categories in our setting. The cost for SR and IR patients is significantly reduced through decreased IP admissions for both, chemotherapy and non-chemotherapy reasons.

Comparison of the dynamics of exoskeletal-assisted and unassisted locomotion in an FDA-approved lower extremity device: Controlled experiments and development of a subject-specific virtual simulator.

Robotic exoskeletons have considerable, but largely untapped, potential to restore mobility in individuals with neurological disorders, and other conditions that result in partial or complete immobilization. The growing demand for these devices necessitates the development of technology to characterize the human-robot system during exoskeletal-assisted locomotion (EAL) and accelerate robot design refinements. The goal of this study was to combine controlled experiments with computational modeling to build a virtual simulator of EAL. The first objective was to acquire a minimum empirical dataset comprising human-robot kinematics, ground reaction forces, and electromyography during exoskeletal-assisted and unassisted locomotion from an able-bodied participant. The second objective was to quantify the dynamics of the human-robot system using a subject-specific virtual simulator reproducing EAL compared to the dynamics of normal gait. We trained an able-bodied participant to ambulate independently in a Food and Drug Administration-approved exoskeleton, the ReWalk P6.0 (ReWalk Robotics, Yoknaem, Israel). We analyzed the motion of the participant during exoskeletal-assisted and unassisted walking, sit-to-stand, and stand-to-sit maneuvers, with simultaneous measurements of (i) three-dimensional marker trajectories, (ii) ground reaction forces, (iii) electromyography, and (iv) exoskeleton encoder data. We created a virtual simulator in OpenSim, comprising a whole-body musculoskeletal model and a full-scale exoskeleton model, to determine the joint kinematics and moments during exoskeletal-assisted and unassisted maneuvers. Mean peak knee flexion angles of the human subject during exoskeletal-assisted walking were 50.1° ± 0.6° (left) and 52.6° ± 0.7° (right), compared to 68.6° ± 0.3° (left) and 70.7° ± 1.1° (right) during unassisted walking. Mean peak knee extension moments during exoskeletal-assisted walking were 0.10 ± 0.10 Nm/kg (left) and 0.22 ± 0.11 Nm/kg (right), compared to 0.64 ± 0.07 Nm/kg (left) and 0.73 ± 0.10 Nm/kg (right) during unassisted walking. This work provides a foundation for parametric studies to characterize the effects of human and robot design variables, and predictive modeling to optimize human-robot interaction during EAL.

Role of Dynamics and Mutations in Interactions of a Zinc Finger Antiviral Protein with CG-rich Viral RNA.

Zinc finger antiviral protein (ZAP) is a host antiviral factor that selectively inhibits the replication of a variety of viruses. ZAP recognizes the CG-enriched RNA sequences and activates the viral RNA degradation machinery. In this work, we investigated the dynamics of a ZAP/RNA complex and computed the energetics of mutations in ZAP that affect its binding to the viral RNA. The crystal structure of a mouse-ZAP/RNA complex showed that RNA interacts with the zinc finger 2 (ZF2) and ZF3 domains. However, we found that due to the dynamic behavior of the single-stranded RNA, the terminal nucleotides C1 and G2 of RNA change their positions from the ZF3 to the ZF1 domain. Moreover, the electrostatic interactions between the zinc ions and the viral RNA provide further stability to the ZAP/RNA complex. We also provide structural and thermodynamic evidence for seven residue pairs (C1-Arg74, C1-Arg179, G2-Arg74, U3-Lys76, C4-Lys76, G5-Arg95, and U6-Glu204) that show favorable ZAP/RNA interactions, although these interactions were not observed in the ZAP/RNA crystal structure. Consistent with the observations from the mouse-ZAP/RNA crystal structure, we found that four residue pairs (C4-Lys89, C4-Leu90, C4-Tyr108, and G5-Lys107) maintained stable interactions in MD simulations. Based on experimental mutagenesis studies and our residue-level interaction analysis, we chose seven residues (Arg74, Lys76, Lys89, Arg95, Lys107, Tyr108, and Arg179) for individual alanine mutations. In addition, we studied mutations in those residues that are only observed in the crystal structures as interacting with RNA (Tyr98, Glu148, and Arg170). Out of these 10 mutations, we found that the Ala mutation in each of the five residues Arg74, Lys76, Lys89, Lys107, and Glu148 significantly reduced the binding affinity of ZAP to RNA.

Botulinum neurotoxin type A improves vasti muscle balance, patellar tracking, and pain in patients with chronic patellofemoral pain.

The purpose of this study was to determine the effects of botulinum neurotoxin type A (BoNT-A) on vastus lateralis:vastus medialis (VL:VM) muscle balance, patellar tracking, and pain in patients with chronic patellofemoral (PF) pain. We recruited 13 participants (9 females, 4 males) with recalcitrant PF pain who underwent ultrasound-guided BoNT-A injections into the distal third of the VL muscle, followed by a 6-week home exercise program to strengthen their VM muscle. We imaged the participants in a C-arm computed tomography (CT) scanner before and after the intervention. We calculated VL:VM ratios from CT images from a supine, nonweight-bearing condition. We obtained patellar tilt and bisect offset values from CT images from an upright, weight-bearing condition. We recorded functional pain scores before, immediately after, and 2-4 years after the intervention. We classified the participants into normal tracking and maltracking groups based on their patellar tilt and bisect offset values. BoNT-A with home exercise reduced VL:VM ratio (18%; p < 0.001), patellar tilt (19%; p = 0.020), and bisect offset (5%; p = 0.025). Four participants classified as maltrackers before the intervention transitioned to normal tracking after the intervention. Functional pain scores improved immediately after the intervention (13%, p < 0.001) and remained improved at 2-year follow-up (12%, p = 0.011). Statement of Clinical Significance: This study provides new evidence in support of BoNT-A for treatment of PF pain. Classification of patients under weight-bearing conditions may identify individuals who will most benefit from a BoNT-A treatment.

Dual Wavelength Photoplethysmography Framework for Heart Rate Calculation.

The quality of heart rate (HR) measurements extracted from human photoplethysmography (PPG) signals are known to deteriorate under appreciable human motion. Auxiliary signals, such as accelerometer readings, are usually employed to detect and suppress motion artifacts. A 2019 study by Yifan Zhang and his coinvestigatorsused the noise components extracted from an infrared PPG signal to denoise a green PPG signal from which HR was extracted. Until now, this approach was only tested on "micro-motion" such as finger tapping. In this study, we extend this technique to allow accurate calculation of HR under high-intensity full-body repetitive "macro-motion". Our Dual Wavelength (DWL) framework was tested on PPG data collected from 14 human participants while running on a treadmill. The DWL method showed the following attributes: (1) it performed well under high-intensity full-body repetitive "macro-motion", exhibiting high accuracy in the presence of motion artifacts (as compared to the leading accelerometer-dependent HR calculation techniques TROIKA and JOSS); (2) it used only PPG signals; auxiliary signals such as accelerometer signals were not needed; and (3) it was computationally efficient, hence implementable in wearable devices. DWL yielded a Mean Absolute Error (MAE) of 1.22|0.57 BPM, Mean Absolute Error Percentage (MAEP) of 0.95|0.38%, and performance index (PI) (which is the frequency, in percent, of obtaining an HR estimate that is within ±5 BPM of the HR ground truth) of 95.88|4.9%. Moreover, DWL yielded a short computation period of 3.0|0.3 s to process a 360-second-long run.

Nonpolar hydrophobic amino acids tune the enzymatic activity of lysozyme.

We have used five different hydrophobic L-amino acids (Gly, Ala, Val, Leu, Ile) as molecular crowders to investigate their role on the enzymatic activity of lysozyme towards Micrococcus lysodeikticus (M. lys.)cell as substrate. We found that except Ile, all other amino acids show a bell like profile of catalytic efficiency (kcat/Km) with their increasing concentration whereas for Ile, the value is gradually increasing. The trend of activation energy (Ea) is also well correlated with the catalytic efficiency of lysozyme. At low concentration of amino acids, soft interaction predominates whereas at higher concentration range, excluded volume, viscosity, hydrophobicity combinedly decrease the activity of lysozyme.

Deciphering the Role of ATP on PHF6 Aggregation.

The aggregation of Tau protein, which are involved in Alzheimer's disease, are associated with the self-assembly of the hexapeptide sequence, paired helical filament 6 (PHF6) from repeat 3 of Tau. In order to treat Alzheimer's disease and other such tauopathies, one of the therapeutic strategies is to inhibit aggregation of Tau and its nucleating segments. Therefore, we have studied the effect of adenosine triphosphate (ATP) on the aggregation of PHF6. ATP has, interestingly, demonstrated its ability to inhibit and dissolve protein aggregates. Using classical molecular dynamics simulations, we observed that the hydrophobic core of PHF6 segment displays extended ß-sheet conformation, which stabilizes PHF6 aggregates. However, the distribution of ATP around the vicinity of the peptides enables PHF6 to remain discrete and attain random coil conformers. The interpeptide interactions are substituted by PHF6-ATP interactions through hydrogen bonding and hydrophobic interactions (including π-π stacking). Furthermore, the adenosine moiety of ATP contributes more than the triphosphate chain toward PHF6-ATP interaction. Ultimately, this work establishes the inhibitory activity of ATP against Tau aggregation; hence, the therapeutic effect of ATP should be explored further in regard to the effective treatment of Alzheimer's disease.

Muscle co-contractions are greater in older adults during walking at self-selected speeds over uneven compared to even surfaces.

Falls in the aging population are a major public health concern. Outdoor falls in community-dwelling older adults are often triggered by uneven pedestrian walkways. Our understanding of the motor control adaptations to walk over an uneven surface, and the effects of aging on these adaptations is sparse. Here, we study changes in muscle co-contraction, a clinically accepted measure of motor control, due to changes in walking surfaces typically encountered in the outdoor built environment. We address the following research questions: 1) are there walking surface and sex-based differences in muscle co-contractions between young and older adults? and 2) is muscle co-contraction associated with age? We calculated muscle co-contractions from 13 young and 17 older adults during walking at self-selected speeds over even and uneven brick walkways. Muscle co-contraction at the ankle joint was determined from the tibialis anterior and lateral gastrocnemius muscle pair, and at the knee joint from the rectus femoris and semitendinosus muscle pair. Older adults displayed 8-13% greater ankle muscle co-contractions during walking over uneven compared to even surfaces. We found 55-61% (entire gait) and 73-75% (stance phase) greater ankle muscle co-contractions in older females compared to older males during walking over even and uneven surfaces. We found 31-43% greater knee muscle co-contractions in older females compared to older males during the swing phase of walking over even and uneven surfaces. This study underscores the need for determining muscle co-contractions from even and uneven surfaces for quantifying motor control deficits due to aging or neuromuscular disorders.

Theoretical investigation of conformational deviation of the human parallel telomeric G-quadruplex DNA in the presence of different salt concentrations and temperatures under confinement.

Various experimental reports address the stability of G-quadruplex DNA inside a close confinement such as α-hemolysin, nanocavity water pool and different metal-organic-frameworks (MOFs). To understand the conformational change of G-quadruplex DNA at the atomistic level, we have carried out a total of 40 µs simulation run under both non-polar and polar confinement conditions. To investigate the dynamics, we have considered two different KCl salt concentrations, i.e., 0.47 M (minimal salt concentration) and higher than 2 M (higher salt concentration), at two distinct temperatures, 300 K and 350 K. Here, we have observed that the human telomeric G-quadruplex DNA deviates more from its crystal structure at minimal salt concentration under both non-polar and polar confinement conditions. Besides, the loop regions deviate and fluctuate more compared to the other regions, i.e., sugar-phosphate backbone and tetrad regions. The presence of K+ ions is found to be primarily responsible for this phenomenon. From the spatial density function (SDF) plots, a higher density of K+ ions is observed in the backbone region. Furthermore, from the residue-wise first solvation shell estimation, we have noticed that the K+ ions mainly accumulate in the tetrad region under both non-polar and polar confinement conditions due to which the tetrad regions are more rigid than the loop regions. Higher salt concentration results in increased rigidity of the G-quadruplex DNA. Our study provides valuable insight into the conformational deviation of the G-quadruplex DNA under nanoconfinement conditions.

Development of sub-tropically adapted diverse provitamin-A rich maize inbreds through marker-assisted pedigree selection, their characterization and utilization in hybrid breeding.

Malnutrition has emerged as one of the major health problems worldwide. Traditional yellow maize has low provitamin-A (proA) content and its genetic base in proA biofortification breeding program of subtropics is extremely narrow. To diversify the proA rich germplasm, 10 elite low proA inbreds were crossed with a proA rich donor (HP702-22) having mutant crtRB1 gene. The F2 populations derived from these crosses were genotyped using InDel marker specific to crtRB1. Severe marker segregation distortion was observed. Seventeen crtRB1 inbreds developed through marker-assisted pedigree breeding and seven inbreds generated using marker-assisted backcross breeding were characterized using 77 SSRs. Wide variation in gene diversity (0.08 to 0.79) and dissimilarity coefficient (0.28 to 0.84) was observed. The inbreds were grouped into three major clusters depicting the existing genetic diversity. The crtRB1-based inbreds possessed high ß-carotene (BC: 8.72µg/g), ß-cryptoxanthin (BCX: 4.58µg/g) and proA (11.01µg/g), while it was 2.35µg/g, 1.24µg/g and 2.97µg/g in checks, respectively. Based on their genetic relationships, 15 newly developed crtRB1-based inbreds were crossed with five testers (having crtRB1 gene) using line × tester mating design. 75 experimental hybrids with crtRB1 gene were evaluated over three locations. These experimental hybrids possessed higher BC (8.02µg/g), BCX (4.69µg/g), proA (10.37µg/g) compared to traditional hybrids used as check (BC: 2.36 µg/g, BCX: 1.53µg/g, proA: 3.13µg/g). Environment and genotypes × environment interaction had minor effects on proA content. Both additive and dominance gene action were significant for proA. The mean proportion of proA to total carotenoids (TC) was 44% among crtRB1-based hybrids, while 11% in traditional hybrids. BC was found to be positively correlated with BCX (r = 0.68) and proA (r = 0.98). However, no correlation was observed between proA and grain yield. Several hybrids with >10.0 t/ha grain yield with proA content >10.0 µg/g were identified. This is the first comprehensive study on development of diverse proA rich maize hybrids through marker-assisted pedigree breeding approach. The findings provides sustainable and cost-effective solution to alleviate vitamin-A deficiency.

An in silico investigation of the binding modes and pathway of APTO-253 on c-KIT G-quadruplex DNA.

The stability of c-KIT G-quadruplex DNA via ligands has been a significant concern in the growing field of cancer therapy. Thus, it is very important to understand the mechanism behind the high binding affinity of the small drug molecules on the c-KIT G-quadruplex DNA. In this study, we have investigated the binding mode and pathway of the APTO-253 ligand on the c-KIT G-quadruplex DNA employing a total of 10 µs all atom molecular dynamics simulations and further 8.82 µs simulations via the umbrella sampling method using both OL15 and BSC1 latest force fields for DNA structures. From the cluster structure analysis, mainly three binding pathways i.e., top, bottom and side loop stacking modes are identified. Moreover, RMSD, RMSF and 2D-RMSD values indicate that the c-KIT G-quadruplex DNA and APTO-253 molecules are stable throughout the simulation run. Furthermore, the number of hydrogen bonds in each tetrad and the distance between the two central K+ cations confirm that the c-KIT G-quadruplex DNA maintains its conformation in the process of complex formation with the APTO-253 ligand. The binding free energies and the minimum values in the potential of mean forces suggest that the binding processes are energetically favorable. Furthermore, we have found that the bottom stacking mode is the most favorable binding mode among all the three modes for the OL15 force field. However, for the BSC1 force field, both the top and bottom binding modes of the APTO-253 ligand in c-KIT G-quadruplex DNA are comparable to each other. To investigate the driving force for the complex formation, we have noticed that the van der Waals (vdW) and π-π stacking interactions are mainly responsible. Our detailed studies provide useful information for the discovery of novel drugs in the field of stabilization of G-quadruplex DNAs.

Tibiofemoral forces during FES rowing in individuals with spinal cord injury.

The purpose of this study is to determine the tibiofemoral forces during functional electrical stimulation (FES) rowing in individuals with spinal cord injury (SCI). We analysed the motion of five participants with SCI during FES rowing, with simultaneous measurements of (i) three-dimensional marker trajectories, (ii) foot reaction forces (FRFs), (iii) ergometer handle forces, and (iv) timestamps for electrical stimulation of the quadriceps and hamstrings muscles. We created full-body musculoskeletal models in OpenSim to determine subject-specific tibiofemoral forces during FES rowing. The peak magnitudes of tibiofemoral forces averaged over five participants with SCI were 2.43 ± 0.39 BW and 2.25 ± 0.71 BW for the left and right legs, respectively. The peak magnitudes of FRFs were 0.19 ± 0.04 BW in each leg. The peak magnitude of handle forces was 0.47 ± 0.19 BW. Peak tibiofemoral force was associated with peak FRF (magnitudes, R2 = 0.56, p = 0.013) and peak handle force (magnitudes, R2 = 0.54, p = 0.016). The ratios of peak magnitude of tibiofemoral force to peak magnitude of FRF were 12.9 ± 1.9 (left) and 11.6 ± 2.4 (right), and to peak magnitude of handle force were 5.7 ± 2.3 (left) and 4.9 ± 0.9 (right). This work lays the foundation for developing a direct exercise intensity metric for bone mechanical stimulus at the knee during rehabilitation exercises. Clinical Significance: Knowledge of tibiofemoral forces from exercises such as FES rowing may provide clinicians the ability to personalize rehabilitation protocols to ensure that an SCI patient is receiving the minimum dose of mechanical stimulus necessary to maintain bone health.

Antiviral Strategies Using Natural Source-Derived Sulfated Polysaccharides in the Light of the COVID-19 Pandemic and Major Human Pathogenic Viruses.

Only a mere fraction of the huge variety of human pathogenic viruses can be targeted by the currently available spectrum of antiviral drugs. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the urgent need for molecules that can be deployed quickly to treat novel, developing or re-emerging viral infections. Sulfated polysaccharides are found on the surfaces of both the susceptible host cells and the majority of human viruses, and thus can play an important role during viral infection. Such polysaccharides widely occurring in natural sources, specifically those converted into sulfated varieties, have already proved to possess a high level and sometimes also broad-spectrum antiviral activity. This antiviral potency can be determined through multifold molecular pathways, which in many cases have low profiles of cytotoxicity. Consequently, several new polysaccharide-derived drugs are currently being investigated in clinical settings. We reviewed the present status of research on sulfated polysaccharide-based antiviral agents, their structural characteristics, structure-activity relationships, and the potential of clinical application. Furthermore, the molecular mechanisms of sulfated polysaccharides involved in viral infection or in antiviral activity, respectively, are discussed, together with a focus on the emerging methodology contributing to polysaccharide-based drug development.

Conjugation reaction with ferulic acid boosts the antioxidant property of arabinogalactan-protein and enhances its ability to form complex with ß-lactoglobulin.

Ferulic acid was chemically grafted onto the arabinogalactan protein of Aegle marmelos fruit gum using 1,1'-carbonyldiimidazole as coupling reagent. Thus, grafted polysaccharides with different degrees of substitution were prepared and then characterized by gas chromatography/mass spectrometry, size exclusion chromatography, and ultraviolet-visible, infra-red, and nuclear magnetic resonance spectroscopic investigations. Fluorescence spectroscopic investigation showed hydrophobic microdomain formation in grafted polymers. The antioxidant activities of the derivatives, as determined by the 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl radical assay, were strong and increases with increasing the degree of feruloylation. Compared to parental arabinogalactan protein (K = 2.38 × 106 M-1), these grafted polymers bind more strongly with ß-lactoglobulin (K = 11.4 × 106 M-1 and 8.19 × 106 M-1). Given that gum polysaccharides are valuable component in functional foods, synthesis of antioxidative graft polymer possessing good compatibility with ß-lactoglobulin may have important implication.

The heteropolysaccharide of Mangifera indica fruit: Isolation, chemical profile, complexation with ß-lactoglobulin and antioxidant activity.

A 91 kDa heteropolysaccharide (F2) was isolated from Mangifera indica fruit via extraction with H2O, purification by C2H5OH, starch removal and ion exchange chromatography. This polymer was made up mostly of Ara, Gal, Glc, Rha, Xyl, and GalA in a 37: 29: 9:3:2:19 molar proportion. It inherited a small backbone containing GalpA and Rhap units substituted with very large side chains containing differently linked Ara and Gal units plus esterified gallic acid (GA) residue. Several enzymes generated oligosaccharides including (i) Ara2-10Ac6-22, (ii) Gal1-8Ac5-26 and (iii) GA1Gal1Ac7 were characterized. This polysaccharide, which showed dose dependent antioxidant activity, exhibited synergism with gallic acid, and formed a complex (K = 1.2 × 106 M-1) with ß-lactoglobulin. Accordingly, H2O treatment produces a polysaccharide with desired biochemical properties; this could be effective in designing innovative functional food with flexible makeup.

Potential of a Natural Deep Eutectic Solvent, Glyceline, in the Thermal Stability of the Trp-Cage Mini-protein.

Deep eutectic solvents (DESs) are the new class of green and inexpensive anhydrous solvents, which are alternatives of ionic liquids. The applications of these promising anhydrous sustainable solvents in biological media have been explored. However, the behavior and stability of biomolecules in DES are not clearly understood. In this study, we have investigated the stability of Trp-cage mini-protein in glyceline, which is a natural deep eutectic mixture (NADES) of choline chloride and glycerol. A series of all-atom molecular dynamics at different temperatures are carried out, and it is found that the protein is stable at much higher temperatures in a DES solvent than in water medium. It is observed that at 400 K this protein denatures from its native state in water medium whereas it retains its native structure up to 400 K temperature in DES medium. Through various analyses, it is also noticed that the interaction between the protein and the glycerol and the choline molecules decreases with the increase in temperature from 300 to 400 K. The crucial parameters, which help in the stabilization of the folded conformation of Trp-cage mini-protein, are maintained in glyceline up to a temperature of 400 K, but they disintegrate at 450 K. The low diffusion coefficient of the glyceline molecules helps to maintain the folded conformation of Trp-cage, which increases at high temperature, causing distortion in the stable interactions between the mini-protein and the solvent molecules. This ultimately leads to the unfolding of the mini-protein. Since Trp-cage mini-protein is a prototypical protein, the thermal stability of this protein in this NADES proves this solvent as an ideal medium for biocatalytic reactions and long-time storage of biomolecules.