Solar-Driven Ammonia Production through Engineering of the Electronic Structure of a Zr-Based MOF.

As a hydrogen carrier and a vital component in fertilizer production, ammonia (NH3) is set to play a crucial role in the planet's future. While its industrial production feeds half of the global population, it uses fossil fuels and emits greenhouse gases. To tackle this issue, photocatalytic nitrogen fixation using visible light is emerging as an effective alternative method. This strategy avoids carbon dioxide (CO2) emissions and harnesses the largest share of sunlight. In this work, we successfully incorporated a 5-nitro isophthalic acid linker into MOF-808 to introduce structural defects and open metal sites. This has allowed modulation of the electronic structure of the MOF and effectively reduced the band gap energy from 3.8 to 2.6 eV. Combination with g-C3N4 enhanced further NH3 production, as these two materials possess similar band gap energies, and g-C3N4 has shown excellent performance for this reaction. The nitro groups serve as acceptors, and their integration into the MOF structure allowed effective interaction with the free electron pairs on N-(C)3 in the g-C3N4 network nodes. Based on DFT calculations, it was concluded that the adsorption of N2 molecules on open metal sites caused a decrease in their triple bond energy. The modified MOF-808 showed superior performance compared with the other MOFs studied in terms of N2 photoreduction under visible light. This design concept offers valuable information about how to engineer band gap energy in MOF structures and their combination with appropriate semiconductors for solar-powered photocatalytic reactions, such as N2 or CO2 photoreduction.

Sulfonated Zinc Phthalocyanine Coating as an Efficient and Ecofriendly Corrosion Inhibitor for Copper Surfaces: An In Silico Led Design and Its Experimental Validation.

The current study highlights the successful integration of an in silico design with experimental validation to create a highly effective corrosion inhibitor for copper (Cu) surfaces. The synthesized sulfonated zinc phthalocyanine (Zn-Pc) is electrochemically characterized and demonstrates an impressive 97% inhibition efficiency, comparable to the widely used industrial corrosion inhibitor, BTA, for Cu surfaces. The corrosion inhibition is comprehensively analyzed through potentiodynamic polarization and impedance spectroscopy techniques, supported by their respective equivalent circuits. Furthermore, the sample undergoes thorough characterization using scanning electron microscopy, energy-dispersive X-ray analysis, X-ray photoelectron spectroscopy, contact angle measurements, and atomic force microscopy. Density functional theory calculations reveal that sulfonated Zn-Pc exhibits the highest interaction energy, underscoring its exceptional inhibition properties. These results open possibilities for utilizing computational methods to design and optimize corrosion inhibitors for protection of Cu surfaces.

IndiGenomes: a comprehensive resource of genetic variants from over 1000 Indian genomes.

With the advent of next-generation sequencing, large-scale initiatives for mining whole genomes and exomes have been employed to better understand global or population-level genetic architecture. India encompasses more than 17% of the world population with extensive genetic diversity, but is under-represented in the global sequencing datasets. This gave us the impetus to perform and analyze the whole genome sequencing of 1029 healthy Indian individuals under the pilot phase of the 'IndiGen' program. We generated a compendium of 55,898,122 single allelic genetic variants from geographically distinct Indian genomes and calculated the allele frequency, allele count, allele number, along with the number of heterozygous or homozygous individuals. In the present study, these variants were systematically annotated using publicly available population databases and can be accessed through a browsable online database named as 'IndiGenomes' http://clingen.igib.res.in/indigen/. The IndiGenomes database will help clinicians and researchers in exploring the genetic component underlying medical conditions. Till date, this is the most comprehensive genetic variant resource for the Indian population and is made freely available for academic utility. The resource has also been accessed extensively by the worldwide community since it's launch.

Development of an efficient single-cell cloning and expansion strategy for genome edited induced pluripotent stem cells.

BACKGROUND: Disease-specific human induced pluripotent stem cells (hiPSCs) can be generated directly from individuals with known disease characteristics or alternatively be modified using genome editing approaches to introduce disease causing genetic mutations to study the biological response of those mutations. The genome editing procedure in hiPSCs is still inefficient, particularly when it comes to homology directed repair (HDR) of genetic mutations or targeted transgene insertion in the genome and single cell cloning of edited cells. In addition, genome editing processes also involve additional cellular stresses such as poor cell viability and genetic stability of hiPSCs. Therefore, efficient workflows are desired to increase genome editing application to hiPSC disease models and therapeutic applications. METHODS AND RESULTS: To this end, we demonstrate an efficient workflow for feeder-free single cell clone generation and expansion in both CRISPR-mediated knock-out (KO) and knock-in (KI) hiPSC lines. Using StemFlex medium and CloneR supplement in conjunction with Matrigel cell culture matrix, we show that cell viability and expansion during single-cell cloning in edited and unedited cells is significantly enhanced. Keeping all factors into account, we have successfully achieved hiPSC single-cell survival and cloning in both edited and unedited cells with rates as maximum as 70% in less than 2 weeks. CONCLUSION: This simplified and efficient workflow will allow for a new level of sophistication in generating hiPSC-based disease models to promote rapid advancement in basic research and also the development of novel cellular therapeutics.

Francisella novicida Cas9 interrogates genomic DNA with very high specificity and can be used for mammalian genome editing.

Genome editing using the CRISPR/Cas9 system has been used to make precise heritable changes in the DNA of organisms. Although the widely used Streptococcus pyogenes Cas9 (SpCas9) and its engineered variants have been efficiently harnessed for numerous gene-editing applications across different platforms, concerns remain regarding their putative off-targeting at multiple loci across the genome. Here we report that Francisella novicida Cas9 (FnCas9) shows a very high specificity of binding to its intended targets and negligible binding to off-target loci. The specificity is determined by its minimal binding affinity with DNA when mismatches to the target single-guide RNA (sgRNA) are present in the sgRNA:DNA heteroduplex. FnCas9 produces staggered cleavage, higher homology-directed repair rates, and very low nonspecific genome editing compared to SpCas9. We demonstrate FnCas9-mediated correction of the sickle cell mutation in patient-derived induced pluripotent stem cells and propose that it can be used for precise therapeutic genome editing for a wide variety of genetic disorders.

Impact of sickle cell disease on patients' daily lives, symptoms reported, and disease management strategies: Results from the international Sickle Cell World Assessment Survey (SWAY).

Sickle cell disease (SCD) is a genetic disorder, characterized by hemolytic anemia and vaso-occlusive crises (VOCs). Data on the global SCD impact on quality of life (QoL) from the patient viewpoint are limited. The international Sickle Cell World Assessment Survey (SWAY) aimed to provide insights into patient-reported impact of SCD on QoL. This cross-sectional survey of SCD patients enrolled by healthcare professionals and advocacy groups assessed disease impact on daily life, education and work, symptoms, treatment goals, and disease management. Opinions were captured using a Likert scale of 1-7 for some questions; 5-7 indicated "high severity/impact." Two thousand one hundred and forty five patients (mean age 24.7 years [standard deviation (SD) = 13.1], 39% ≤18 years, 52% female) were surveyed from 16 countries (six geographical regions). A substantial proportion of patients reported that SCD caused a high negative impact on emotions (60%) and school achievement (51%) and a reduction in work hours (53%). A mean of 5.3 VOCs (SD = 6.8) was reported over the 12 months prior to survey (median 3.0 [interquartile range 2.0-6.0]); 24% were managed at home and 76% required healthcare services. Other than VOCs, fatigue was the most commonly reported symptom in the month before survey (65%), graded "high severity" by 67% of patients. Depression and anxiety were reported by 39% and 38% of patients, respectively. The most common patient treatment goal was improving QoL (55%). Findings from SWAY reaffirm that SCD confers a significant burden on patients, epitomized by the high impact on patients' QoL and emotional wellbeing, and the high prevalence of self-reported VOCs and other symptoms.

Evaluation of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata: A randomized observer-blinded, placebo-controlled, split-head pilot study.

BACKGROUND: Platelet-rich plasma has shown some promise in the treatment of alopecia areata. OBJECTIVE: To evaluate the effect of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata. METHODS: This was a randomized, placebo-controlled, split-head study involving 27 patients with alopecia areata (Severity of Alopecia Tool score ≥25%). Alopecia patches on either side of the scalp were randomized to receive 3 intradermal injections of platelet-rich plasma or normal saline at monthly intervals and evaluated 3 months after the last session. Lesional T-cell cytokine messenger RNA expression was compared pre- and posttreatment in the platelet-rich plasma-treated sites. RESULTS: The mean Severity of Alopecia Tool score did not change significantly compared with baseline with either platelet-rich plasma or placebo injections at any visit; however, the mean percentage reduction in the score in the platelet-rich plasma arm was more than in the placebo arm (9.05% ± 36.48% vs 4.99% ± 33.88%; P = .049) at final assessment. The mean interferon gamma (P = .001) and interleukin 17 cytokine (P = .009) messenger RNA expression decreased, whereas the mean interleukin 10 (P = .049) and FOXP3 (P = .011) messenger RNA expression increased significantly after platelet-rich plasma treatment. LIMITATIONS: Small sample size and a relatively short follow-up. CONCLUSION: Platelet-rich plasma was found to have limited efficacy in alopecia areata. However, it may play a role in restoring immune balance in the alopecic patches.

Lithium acts to modulate abnormalities at behavioral, cellular, and molecular levels in sleep deprivation-induced mania-like behavior.

BACKGROUND: Ample amount of data suggests role of rapid eye movement (REM) sleep deprivation as the cause and effect of mania. Studies have also suggested disrupted circadian rhythms contributing to the pathophysiology of mood disorders, including bipolar disorder. However, studies pertaining to circadian genes and effect of lithium treatment on clock genes are scant. Thus, we wanted to determine the effects of REM sleep deprivation on expression of core clock genes and determine whether epigenetics is involved. Next, we wanted to explore ultrastructural abnormalities in the hippocampus. Moreover, we were interested to determine oxidative stress, tumor necrosis factor-α (TNF-α), and brain-derived neurotrophic factor levels in the central and peripheral systems. METHODS: Rats were sleep deprived by the flower pot method and were then analyzed for various behaviors and biochemical tests. Lithium was supplemented in diet. RESULTS: We found that REM sleep deprivation resulted in hyperactivity, reduction in anxiety-like behavior, and abnormal dyadic social interaction. Some of these behaviors were sensitive to lithium. REM sleep deprivation also altered circadian gene expression and caused significant imbalance between histone acetyl transferase/histone deacetylase (HAT/HDAC) activity. Ultrastructural analysis revealed various cellular abnormalities. Lipid peroxidation and increased TNF-α levels suggested oxidative stress and ongoing inflammation. Circadian clock genes were differentially modulated with lithium treatment and HAT/HDAC imbalance was partially prevented. Moreover, lithium treatment prevented myelin fragmentation, disrupted vasculature, necrosis, inflammation, and lipid peroxidation, and partially prevented mitochondrial damage and apoptosis. CONCLUSIONS: Taken together, these results suggest plethora of abnormalities in the brain following REM sleep deprivation, many of these changes in the brain may be target of lithium's mechanism of action.

Identification and Development of a High-Risk District Model in the Prevention of ß-Thalassemia in Telangana State, India.

The burden of ß-thalassemia (ß-thal) is largely underestimated in India with a carrier frequency of 3.0-4.0% in general, whereas highly stratified frequencies of up to 17.0% are reported in local endogamous subpopulations. We have no idea whether ß-thal carrier frequencies or ß-thal major (ß-TM) births are increasing or decreasing in the population. The cross-sectional nature of all carrier screening programs including large-scale task force and micro level, lack of registration of ß-TM births and mechanism to modulate knowledge, awareness programs in a long-term perspective, all preempt impact assessment of preventive programs. During the implementation of a Telangana State Government-sponsored program on 'Micro profiling of ß-thalassemia mutations in Telangana,' we documented extensive in-depth demographic information on each ß-TM child of the study sample that included age-sex distributions, parental and grand-parental ethnic affiliations (local endogamous group level), birth places, marital migrations, endogamy and consanguinity to identify high-risk districts as ethno-geographic regions. In Telangana State, we found ß-thal is widely prevalent in 31 districts and 48 local endogamous subpopulations. The present study provided a method of identification of four 'high-risk districts' and developed a district model for prevention on high priority in Telangana State. The model has the advantage of impact-assessment of all preventive programs in the district.

Neuroregenerative Effects of Electromagnetic Field and Magnetic Nanoparticles on Spinal Cord Injury in Rats.

The present study aimed to evaluate the effect of iron oxide nanoparticles (IONPs) along with electromagnetic fields (MF) exposure on spontaneous and induced axonal sprouting after spinal cord injury (SCI). Adult male Wistar rats were subjected to spinal cord transection at the T13 segment. The IONP (25 µg/mL) embedded in 3% agarose gel was implanted at the injury site and subsequently exposed to MF (50 Hz, 17.96 µT, 2 hours/day for 5 weeks). Histological analysis of spinal cord tissue showed a significant increase in the expression of the growth-associated protein GAP-43 and it was found to be co-localized with neuronal nuclei marker and neurofilaments. The results show sprouting from mature neurons and axons, significantly less demyelination and more myelinated fibers were evident at the lesion site. However, no motor or somatosensory evoked potential response was observed, suggesting lack of long-distance functional connectivity. These findings highlight the therapeutic potential of IONPs along with MF exposure in promoting neuroregeneration after SCI.

High-Resolution Sonography as an Additional Diagnostic and Prognostic Tool to Monitor Disease Activity in Leprosy: A Two-Year Prospective Study.

PURPOSE: Early diagnosis and treatment of leprosy and leprosy reactions are essential to prevent stigmatizing deformities and disability. Although the incidence of leprosy has decreased enormously, grade 2 disability due to nerve injury has remained the same. New tools are needed to better diagnose and monitor leprosy reactions and associated neuritis and this study assessed whether high-resolution sonography (HRUS) can be used as such a tool. MATERIALS AND METHODS: During a prospective follow-up period of 2 years at regular intervals, we performed clinical examination to assess sensory and motor function and HRUS of the four main peripheral nerves in 57 patients, of whom 36 were with reactions and 21 were without reactions. Normative data of the cross-sectional area (CSA) of these nerves were obtained from 55 healthy subjects (HS). Color Doppler (CD) was used to study blood flow in the nerves. RESULTS: At the baseline visit and during follow-up, all four nerves were significantly thicker in patients with leprosy reactions in comparison to HS (p < 0.0001) and to a lesser extent also in comparison to patients without reactions ranging from a p-value of < 0.05 to < 0.0001 in the different nerves tested. During follow-up, the nerve size did not change significantly in patients without reactions, while it decreased significantly in patients with reactions. At baseline, endoneural blood flow was present only in patients with reactions. This occurred in 20 of the 36 (55 %) patients (49 nerves) and decreased to only 1 patient (2.7 %) at the end of the follow-up period. CONCLUSION: This prospective study demonstrates the ability of HRUS to monitor disease activity and the effect of treatment in patients with leprosy reactions by determining changes in nerve size and vascularity, which are indicators of peripheral nerve involvement and damage.

Intra-arterial transplantation of human bone marrow mesenchymal stem cells (hBMMSCs) improves behavioral deficits and alters gene expression in rodent stroke model.

Stroke is a multi-factorial polygenic disease and is a major cause of death and adult disability. Administration of bone marrow stem cells protects ischemic rat brain by facilitating recovery of neurological functions. But the molecular mechanism of stem cells action and their effect on gene expression is not well explored. In this study, we have transplanted 1 × 106 human bone marrow mesenchymal stem cells (hBMMSCs) in middle cerebral artery occluded (MCAo) adult male Wistar rats through intracarotid artery route at 24 h after surgery. Motor behavioral tests (rotarod and open field) were performed to assess the changes in motor functions at day 0 and day1, 4, 8 and 14. The expression of studied genes at mRNA and protein level was quantified by using Q-PCR and western blotting, respectively. Further, we have assessed the methylation pattern of promoter of these genes by using methylation-specific PCR. Data were analyzed statistically and correlated. A significant improvement in behavioral deficits was observed in stem cells treated group after 14th day post stroke. Significantly (p < 0.05) increased mRNA and protein levels of brain derived neurotrophic factor and ANP genes in hBMMSCs treated group along with decrease in methylation level at their promoter was observed. On the other hand, significantly decreased mRNA and protein level of TSP1 and WNK1 in hBMMSCs treated group was observed. In conclusion, hBMMSCs administration significantly improves the behavioral deficits by improving motor and locomotor coordination. The promoter of TSP1 and WNK1 genes was found to be hyper-methylated in hBMMSCs group resulting in their decreased expression while the promoter of ANP and brain derived neurotrophic factor was found to be hypo-methylated. This study might shed a light on how hBMMSCs affect the gene expression by modulating methylation status.

Visible light assisted hydrogen generation from complete decomposition of hydrous hydrazine using rhodium modified TiO2 photocatalysts.

Hydrogen is considered to be an ideal energy carrier, which produces only water when combined with oxygen and thus has no detrimental effect on the environment. While the catalytic decomposition of hydrous hydrazine for the production of hydrogen is well explored, little is known about its photocatalytic decomposition. The present paper describes a highly efficient photochemical methodology for the production of hydrogen through the decomposition of aqueous hydrazine using titanium dioxide nanoparticles modified with a Rh(i) coordinated catechol phosphane ligand (TiO2-Rh) as a photocatalyst under visible light irradiation. After 12 h of visible light irradiation, the hydrogen yield was 413 µmol g-1 cat with a hydrogen evolution rate of 34.4 µmol g-1 cat h-1. Unmodified TiO2 nanoparticles offered a hydrogen yield of 83 µmol g-1 cat and a hydrogen evolution rate of only 6.9 µmol g-1 cat h-1. The developed photocatalyst was robust under the experimental conditions and could be efficiently reused for five subsequent runs without any significant change in its activity. The higher stability of the photocatalyst is attributed to the covalent attachment of the Rh complex, whereas the higher activity is believed to be due to the synergistic mechanism that resulted in better electron transfer from the Rh complex to the conduction band of TiO2.

Investing for Impact: The Global Fund Approach to Measurement of AIDS Response.

The Global Fund raises and invests nearly US$4 billion a year to support programs run in more than 140 countries. The Global Fund strategy 2012-2016 is focused on "Investing for Impact". In order to accomplish this, timely and accurate data are needed to inform strategies and prioritize activities to achieve greater coverage with quality services. Monitoring and evaluation is intrinsic to the Global Fund's system of performance-based funding. The Global Fund invests in strengthening measurement and reporting of results at all stages of the grant cycle. The Global Fund approach to measurement is based on three key principles-(1) simplified reporting: the Global Fund has updated its measurement guidance to focus on impact, coverage and quality with the use of a harmonized set of indicators. (2) Supporting data systems-based on a common framework developed and supported by partners, it promotes investment in five common data systems: routine reporting including HMIS; Surveys-population based and risk group surveys; Analysis, reviews and transparency; Administrative and financial data sources; and, Vital registration systems. (3) Strengthen data use: the Global Fund funding encourages use of data at all levels-national, subnational and site level. Countries do not automatically prioritize M&E but when guidance, tools and investments are available, there is high level utilization of M&E systems in program design, planning, implementation, and results reporting. An in-depth analysis of the available data helps the Global Fund and countries to direct investments towards interventions where impact could be achieved and focus on target population groups and geographic areas that are most affected.

Extremely low-frequency electromagnetic fields: A possible non-invasive therapeutic tool for spinal cord injury rehabilitation.

Traumatic insults to the spinal cord induce both immediate mechanical damage and subsequent tissue degeneration. The latter involves a range of events namely cellular disturbance, homeostatic imbalance, ionic and neurotransmitters derangement that ultimately result in loss of sensorimotor functions. The targets for improving function after spinal cord injury (SCI) are mainly directed toward limiting these secondary injury events. Extremely low-frequency electromagnetic field (ELF-EMF) is a possible non-invasive therapeutic intervention for SCI rehabilitation which has the potential to constrain the secondary injury-induced events. In the present review, we discuss the effects of ELF-EMF on experimental and clinical SCI as well as on biological system.

Extremely low frequency magnetic field protects injured spinal cord from the microglia- and iron-induced tissue damage.

Spinal cord injury (SCI) is insult to the spinal cord, which results in loss of sensory and motor function below the level of injury. SCI results in both immediate mechanical damage and secondary tissue degeneration. Following traumatic insult, activated microglia release proinflammatory cytokines and excess iron due to hemorrhage, initiating oxidative stress that contributes to secondary degeneration. Literature suggests that benefits are visible with the reduction in concentration of iron and activated microglia in SCI. Magnetic field attenuates oxidative stress and promotes axonal regeneration in vitro and in vivo. The present study demonstrates the potential of extremely low frequency magnetic field to attenuate microglia- and iron-induced secondary injury in SCI rats. Complete transection of the spinal cord (T13 level) was performed in male Wistar rats and subsequently exposed to magnetic field (50 Hz,17.96 µT) for 2 h daily for 8 weeks. At the end of the study period, spinal cords were dissected to quantify microglia, macrophage, iron content and study the architecture of lesion site. A significant improvement in locomotion was observed in rats of the SCI + MF group as compared to those in the SCI group. Histology, immunohistochemistry and flow cytometry revealed significant reduction in lesion volume, microglia, macrophage, collagen tissue and iron content, whereas, a significantly higher vascular endothelial growth factor expression around the epicenter of the lesion in SCI + MF group as compared to SCI group. These novel findings suggest that exposure to ELF-MF reduces lesion volume, inflammation and iron content in addition to facilitation of angiogenesis following SCI.

A Prussian blue/carbon dot nanocomposite as an efficient visible light active photocatalyst for C-H activation of amines.

A Prussian blue/carbon dot (PB/CD) nanocomposite was synthesised and used as a visible-light active photocatalyst for the oxidative cyanation of tertiary amines to α-aminonitriles by using NaCN/acetic acid as a cyanide source and H2O2 as an oxidant. The developed photocatalyst afforded high yields of products after 8 h of visible light irradiation at room temperature. The catalyst was recycled and reused several times without any significant loss in its activity.

Neuroprotective Potential of Superparamagnetic Iron Oxide Nanoparticles Along with Exposure to Electromagnetic Field in 6-OHDA Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting mainly the dopaminergic neurons of the substantia nigra leading to various motor and non-motor deficits. We explored the neuroprotective potential of superparamagnetic iron oxide nanoparticles (IONPs) along with exposure to EMF in 6-OHDA rat model of PD. IONPs were implanted at the site of lesion and 24 h thereafter the rats were exposed to magnetic fields 2 h/day for one week. Bilateral lesions of the striatum were made with 6-OHDA. The rats in all the intervention groups improved progressively over the days and by post-surgery day 4 they were active and bright. We observed a significant beneficial effect of the IONPs implantation and MF exposure on feeding behavior, gait and postural stability. There was a significant enhancement of mitochondrial function and attenuation of lesion volume in all the intervention groups as compared to PD. The results demonstrate neuroprotective effect of iron oxide nanoparticle implantation and magnetic field exposure in an in vivo 6-OHDA rat model of PD.

Graphene oxide supported molybdenum cluster: first heterogenized homogeneous catalyst for the synthesis of dimethylcarbonate from CO2 and methanol.

The octahedral molybdenum cluster-based compound, Cs2 Mo6 Br(i) 8 Br(a) 6 was immobilized on graphene oxide (GO) by using a facile approach. High resolution transmission electron microscopy results revealed that molybdenum clusters were uniformly distributed on the GO nanosheets. Cs2 Mo6 Br(i) 8 Br(a) 6 was attached to the GO support via chemical interaction between apical ligands of Mo6 Br(i) 8 Br(a) 6 cluster units and oxygen functionalities of GO, as revealed by XPS studies. The developed material was used for the synthesis of dimethyl carbonate by reduction of carbon dioxide. The synthesized catalyst, that is, GO-Cs2 Mo6 Br(i) 8 Br(a) x , exhibited higher catalytic efficiency than its homogeneous analogue without using dehydrating agent. The catalyst was found to be efficiently recyclable without significant loss of catalytic activity.