PARP1 UFMylation ensures the stability of stalled replication forks.

The S-phase checkpoint involving CHK1 is essential for fork stability in response to fork stalling. PARP1 acts as a sensor of replication stress and is required for CHK1 activation. However, it is unclear how the activity of PARP1 is regulated. Here, we found that UFMylation is required for the efficient activation of CHK1 by UFMylating PARP1 at K548 during replication stress. Inactivation of UFL1, the E3 enzyme essential for UFMylation, delayed CHK1 activation and inhibits nascent DNA degradation during replication blockage as seen in PARP1-deficient cells. An in vitro study indicated that PARP1 is UFMylated at K548, which enhances its catalytic activity. Correspondingly, a PARP1 UFMylation-deficient mutant (K548R) and pathogenic mutant (F553L) compromised CHK1 activation, the restart of stalled replication forks following replication blockage, and chromosome stability. Defective PARP1 UFMylation also resulted in excessive nascent DNA degradation at stalled replication forks. Finally, we observed that PARP1 UFMylation-deficient knock-in mice exhibited increased sensitivity to replication stress caused by anticancer treatments. Thus, we demonstrate that PARP1 UFMylation promotes CHK1 activation and replication fork stability during replication stress, thus safeguarding genome integrity.

Structural basis for enzymatic photocatalysis in chlorophyll biosynthesis.

The enzyme protochlorophyllide oxidoreductase (POR) catalyses a light-dependent step in chlorophyll biosynthesis that is essential to photosynthesis and, ultimately, all life on Earth1-3. POR, which is one of three known light-dependent enzymes4,5, catalyses reduction of the photosensitizer and substrate protochlorophyllide to form the pigment chlorophyllide. Despite its biological importance, the structural basis for POR photocatalysis has remained unknown. Here we report crystal structures of cyanobacterial PORs from Thermosynechococcus elongatus and Synechocystis sp. in their free forms, and in complex with the nicotinamide coenzyme. Our structural models and simulations of the ternary protochlorophyllide-NADPH-POR complex identify multiple interactions in the POR active site that are important for protochlorophyllide binding, photosensitization and photochemical conversion to chlorophyllide. We demonstrate the importance of active-site architecture and protochlorophyllide structure in driving POR photochemistry in experiments using POR variants and protochlorophyllide analogues. These studies reveal how the POR active site facilitates light-driven reduction of protochlorophyllide by localized hydride transfer from NADPH and long-range proton transfer along structurally defined proton-transfer pathways.

Phenotyping COVID-19 respiratory failure in spontaneously breathing patients with AI on lung CT-scan.

BACKGROUND: Automated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes. METHODS: This is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7 days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories. RESULTS: Complete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar-hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables. CONCLUSIONS: Integrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020.

Therapeutic Potential of Phenolic Compounds in Medicinal Plants-Natural Health Products for Human Health.

Phenolic compounds and flavonoids are potential substitutes for bioactive agents in pharmaceutical and medicinal sections to promote human health and prevent and cure different diseases. The most common flavonoids found in nature are anthocyanins, flavones, flavanones, flavonols, flavanonols, isoflavones, and other sub-classes. The impacts of plant flavonoids and other phenolics on human health promoting and diseases curing and preventing are antioxidant effects, antibacterial impacts, cardioprotective effects, anticancer impacts, immune system promoting, anti-inflammatory effects, and skin protective effects from UV radiation. This work aims to provide an overview of phenolic compounds and flavonoids as potential and important sources of pharmaceutical and medical application according to recently published studies, as well as some interesting directions for future research. The keyword searches for flavonoids, phenolics, isoflavones, tannins, coumarins, lignans, quinones, xanthones, curcuminoids, stilbenes, cucurmin, phenylethanoids, and secoiridoids medicinal plant were performed by using Web of Science, Scopus, Google scholar, and PubMed. Phenolic acids contain a carboxylic acid group in addition to the basic phenolic structure and are mainly divided into hydroxybenzoic and hydroxycinnamic acids. Hydroxybenzoic acids are based on a C6-C1 skeleton and are often found bound to small organic acids, glycosyl moieties, or cell structural components. Common hydroxybenzoic acids include gallic, syringic, protocatechuic, p-hydroxybenzoic, vanillic, gentistic, and salicylic acids. Hydroxycinnamic acids are based on a C6-C3 skeleton and are also often bound to other molecules such as quinic acid and glucose. The main hydroxycinnamic acids are caffeic, p-coumaric, ferulic, and sinapic acids.

Traditional herbal medicines to overcome stress, anxiety and improve mental health in outbreaks of human coronaviruses.

Mental health condition is including depression and anxiety, and they may impact wellbeing, personal relationships and productivity of both genders. Herbal medicines have been used to treatment of anxiety and depression symptoms for centuries. SARS, MERS and COVID-19 are related to coronavirus types. SARS (sever acute respiratory syndrome, China, 2002), MERS (Middle East respiratory syndrome, Saudi Arabia, 2012), and SARS-CoV-2 (2019-2020) are the main coronavirus outbreaks. Both anxiety and depression are more serious to be considered and improved for all general public during fight with these diseases. In this mini-review article, we have mentioned the key role some of the most important plants and herbs for treatment of stress and anxiety and improve mental health against SARS and SARS-CoV-2 on the basis of traditional Asian medicine, especially traditional Chinese and Persian medicine.

Analysis of Potential Amino Acid Biomarkers in Brain Tissue and the Effect of Galangin on Cerebral Ischemia.

Galangin, a potent scavenger of free radicals, has been used as an herbal medicine for various ailments for centuries in Asia. With complex pathophysiology, ischemic stroke is one of the most frequent causes of death and disability worldwide. We have reported that galangin provides direct protection against ischemic injury as a potential neuroprotective agent and has potential therapeutic effects on the changes of serum amino acids in ischemic stroke; however, the mechanism of the changes of amino acids in the ischemic brain tissue has not yet been clarified. In this paper, we explored brain tissue amino acid biomarkers in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers. Finally, we identified that glutamic acid, alanine and aspartic acid showed significant changes (p < 0.05 or p < 0.01) in galangin-treated groups compared with vehicle-treated rats and the four enzymes associated with these three AAs' metabolic pathways; GLUD1, SLC16A10, SLC1A1 and GPT were identified by multiplex interactions with the three amino acids. By metabolite-protein network analysis and molecular docking, six of 28 proteins were identified and might become potential galangin biomarkers for acute ischemic stroke. The data in our study provides thoughts for exploring the mechanism of disease, discovering new targets for drug candidates and elucidating the related regulatory signal network.

Volumetric Cortical Bone Porosity Assessment with MR Imaging: Validation and Clinical Feasibility.

PURPOSE: To develop a method to assess volumetric cortical bone porosity in clinically practical acquisition times by measuring the signal decay at only two echo times (TEs) as part of a single three-dimensional ultrashort TE (UTE) magnetic resonance (MR) examination. MATERIALS AND METHODS: The study was approved by the institutional review board and complied with HIPAA guidelines. Written informed consent was obtained from all subjects. A marker of cortical bone porosity called porosity index was defined as the ratio of UTE image intensities at a long and short TE, and the results were compared with biexponential analysis. Porosity index of midtibia cortical bone samples obtained from 16 donors was compared with ground-truth porosity by using micro-computed tomographic (CT) imaging and bone mineral density by peripheral quantitative CT scanner. Reproducibility of porosity index were tested in volunteers, and clinical feasibility was evaluated in postmenopausal women. Interparameter associations were assessed by using Pearson or Spearman correlation coefficient. RESULTS: Bone specimen porosity index was correlated with micro-CT imaging porosity (R(2) = 0.79) and pore size (R(2) = 0.81); age (R(2) = 0.64); peripheral quantitative CT scanner density (R(2) = 0.49, negatively); and pore water fraction (R(2) = 0.62) and T2* (R(2) = 0.64) by biexponential analysis. The reproducibility study yielded a coefficient of variation of 2.2% and intraclass correlation coefficient of 0.97. The study that involved postmenopausal women showed a wide range of porosity index (15%-38%). CONCLUSION: A two-point MR imaging method to assess cortical bone porosity in humans was conceived and validated. This approach has the potential for clinical use to assess changes in cortical bone porosity that result from disease or in response to therapy. (©) RSNA, 2015 Online supplemental material is available for this article.

Cortical bone water concentration: dependence of MR imaging measures on age and pore volume fraction.

PURPOSE: To quantify bulk bone water to test the hypothesis that bone water concentration (BWC) is negatively correlated with bone mineral density (BMD) and is positively correlated with age, and to propose the suppression ratio (SR) (the ratio of signal amplitude without to that with long-T2 suppression) as a potentially stronger surrogate measure of porosity, which is evaluated ex vivo and in vivo. MATERIALS AND METHODS: Human subject studies were conducted in compliance with institutional review board and HIPAA regulations. Healthy men and women (n = 72; age range, 20-80 years) were examined with a hybrid radial ultrashort echo time magnetic resonance (MR) imaging sequence at 3.0 T, and BWC was determined in the tibial midshaft. In a subset of 40 female subjects, the SR was measured with a similar sequence. Cortical volumetric BMD (vBMD) was measured by means of peripheral quantitative computed tomography (CT). The method was validated against micro-CT-derived porosity in 13 donor human cortical bone specimens. Associations among parameters were evaluated by using standard statistical tools. RESULTS: BWC was positively correlated with age (r = 0.52; 95% confidence interval [CI]: 0.22, 0.73; P = .002) and negatively correlated with vBMD at the same location (r = -0.57; 95% CI: -0.76, -0.29; P < .001). Data were suggestive of stronger associations with SR (r = 0.64, 95% CI: 0.39, 0.81, P < .001 for age; r = -0.67, 95% CI: -0.82, -0.43, P < .001 for vBMD; P < .001 for both), indicating that SR may be a more direct measure of porosity. This interpretation was supported by ex vivo measurements showing SR to be strongly positively correlated with micro-CT porosity (r = 0.88; 95% CI: 0.64, 0.96; P < .001) and with age (r = 0.87; 95% CI: 0.62, 0.96; P < .001). CONCLUSION: The MR imaging-derived SR may serve as a biomarker for cortical bone porosity that is potentially superior to BWC, but corroboration in larger cohorts is indicated.

Mechanism of Action of Collagen and Epidermal Growth Factor: A Review on Theory and Research Methods.

The most abundant protein found in mammals is collagen, and there are around 28 different types of collagen found in the human body, but there are five types, namely, Type I, Type II, Type III, Type V, and Type X, most generally applied in supplements, and the five common types of collagen are available in various forms and form different sources, which result in various potential benefits. The epidermal growth factor is one of the main growth factor proteins in the skin, which has an important function in the production of collagen, hyaluronic acid, and elastin to keep the skin healthy and dense appearance. It is a single-chain polypeptide of 53 amino acids, which is a potent mitogen for a variety of cells in vivo and in vitro. It triggers cells to grow, produce, and divide proteins, such as collagen. It may increase collagen production in granulation tissue by stimulation of fibroblast proliferation. This review article aims to provide an overview of different collagens and epidermal growth factors from recently published studies and some important directions for future research. The key words search for Collagen, Epidermal growth, Polypeptides, Amino acids, Protein, and tissue engineering were performed using Google scholar, PubMed, and Scopus. Fibrillar collagens are collagen types I, II, III, V, XI, XXIV, XXVII, and non-fibrillar collagens are collagen types IV, VI, VII, VIII, IX, X, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXV, XXVI, XXVIII, and XXIX. Collagen I can be found in bone, skin, tendon, cornea and vascular ligature; collagen II can be discovered in cartilage, vitreous body and gristle; collagen III is the main ingredient of reticular fibers which is often found alongside type I, the location of collagen III is also in skin, uterus, intestine, and vessels. Collagen IV can be identified in capillaries, the epithelium-secreted layer of the basement membrane and forms basal lamina. It forms basal lamina, capillaries, and the epitheliumsecreted layer of the basement membrane, while Collagen V can be discovered in bones, skin, cornea, hair, placenta, and cell surfaces. In addition, collagen VI is found in bones, skin, gristle, cornea and vessels, while collagen VII can be found in skin, bladder, mucous membranes, amniotic fluid and umbilical cord. Lastly, collagen VIII is found in the skin, heart, kidney, brain, bones, gristle and vessels. Moreover, collagen X, XI and IX can be found in the gristle.

The Power of the Underutilized and Neglected Medicinal Plants and Herbs of the Middle East.

The Middle east and North Africa harbour many native species with pharmaceutical and nutraceutical potential. Since the beginning of history, food and herbal medicinal plants have been an essential part of human lives and the traditional Middle Eastern healthcare system. The notable medicinal plants that have been mentioned in the Bible, which are common in West Asia and some regions of North Africa, are Aloe vera, anise, balm, cassia, cinnamon, cumin, flax, and fig. Chemical components of Aloe vera are aloin, sinapinic acid, catechin, chromone, myricetin, quercitrin and syringic acid. Anethole, safrole, and estragole are the main chemical components of anise. The chemical components of cassia are coumarin, emodin, cinnamyl alcohol, and cinnamaldehyde. The major chemical ingredients of cumin are terpinene, cuminaldehyde, sabinene, thujene, and thymoquinone. The goal of this article is to review the considerable health benefits and pharmaceutical benefits of medicinal herbs and plants that have been neglected and underutilized in the Middle East and North Africa, as well as to promote their utilization. On the basis of the results, the experimented neglected medicinal plant can offer various advantages when used together with conventional medicinal treatments for various health conditions, such as palliative care in managing the side effects of conventional treatments, access to a wider range of treatments, increased patient satisfaction, and improved emotional and mental well-being. Moreover-, consuming medicinal plants may help to manage and prevent diabetes, cancer, and heart disease with notable anti-tumor, and anti-inflammatory properties.

Characterization of Intrinsically Disordered Proteins in Healthy and Diseased States by Nuclear Magnetic Resonance.

Intrinsically Disordered Proteins (IDPs) are active in different cellular procedures like ordered assembly of chromatin and ribosomes, interaction with membrane, protein, and ligand binding, molecular recognition, binding, and transportation via nuclear pores, microfilaments and microtubules process and disassembly, protein functions, RNA chaperone, and nucleic acid binding, modulation of the central dogma, cell cycle, and other cellular activities, post-translational qualification and substitute splicing, and flexible entropic linker and management of signaling pathways. The intrinsic disorder is a precise structural characteristic that permits IDPs/IDPRs to be involved in both one-to-many and many-to-one signaling. IDPs/IDPRs also exert some dynamical and structural ordering, being much less constrained in their activities than folded proteins. Nuclear magnetic resonance (NMR) spectroscopy is a major technique for the characterization of IDPs, and it can be used for dynamic and structural studies of IDPs. This review was carried out to discuss intrinsically disordered proteins and their different goals, as well as the importance and effectiveness of NMR in characterizing intrinsically disordered proteins in healthy and diseased states.

Progress in novel delivery technologies to improve efficacy of therapeutic antibodies.

Monoclonal antibody-based therapeutics have achieved remarkable success in treating a wide range of human diseases. However, conventional systemic delivery methods have limitations in insufficient target tissue permeability, high costs, repeated administrations, etc. Novel technologies have been developed to address these limitations and further enhance antibody therapy. Local antibody delivery via respiratory tract, gastrointestinal tract, eye and blood-brain barrier have shown promising results in increasing local concentrations and overcoming barriers. Nucleic acid-encoded antibodies expressed from plasmid DNA, viral vectors or mRNA delivery platforms also offer advantages over recombinant proteins such as sustained expression, rapid onset, and lower costs. This review summarizes recent advances in antibody delivery methods and highlights innovative technologies that have potential to expand therapeutic applications of antibodies.

The Significance and Importance of dPCR, qPCR, and SYBR Green PCR Kit in the Detection of Numerous Diseases.

Digital PCR (dPCR) is the latest technique that has become commercially accessible for various types of research. This method uses Taq polymerase in a standard polymerase chain reaction (PCR) to amplify a target DNA fragment from a complex sample, like quantitative PCR (qPCR) and droplet digital PCR (dd- PCR). ddPCR may facilitate microRNA (miRNA) measurement, particularly in liquid biopsy, because it has been proven to be more effective and sensitive, and in this method, ddPCR can provide an unprecedented chance for deoxyribonucleic acid (DNA) methylation research because of its capability to increase sensitivity and precision over conventional PCR-based methods. qPCR has also been found to be a valuable standard technique to measure both copy DNA (cDNA) and genomic DNA (gDNA) levels, although the finding data can be significantly variable and non-reproducible without relevant validation and verification of both primers and samples. The SYBR green quantitative real-time PCR (qPCR) method has been reported as an appropriate technique for quantitative detection and species discrimination, and has been applied profitably in different experiments to determine, quantify, and discriminate species. Although both TaqMan qRT-PCR and SYBR green qRT-PCR are sensitive and rapid, the SYBR green qRT-PCR assay is easy and the TaqMan qRT-PCR assay is specific but expensive due to the probe required. This review aimed to introduce dPCR, qPCR, SYBR green PCR kit, and digital PCR, compare them, and also introduce their advantages in the detection of different diseases.

Study on Rapid, Quantitative, and Simultaneous Detection of Drug Residues and Immunoassay in Chickens.

Different levels of residual drugs can be monitored within a relatively safe range without causing harm to human health if the appropriate dosing methodology is considered and the drug withdrawal period is controlled during poultry and livestock raising. Antimicrobials are factors that can suppress the growth of microorganisms, and antibiotic residues in livestock farming have been considered as a potential cause of antimicrobial resistance in animals and humans. Antimicrobial drug resistance is associated with the capability of a microorganism to survive the inhibitory effects of the antimicrobial components. Antibiotic residue presence in chicken is a human health concern due to its negative effects on consumer health. Neglected aspects related to the application of veterinary drugs may threaten the safety of both humans and animals, as well as their environment. The detection of chemical contaminants is essential to ensure food quality. The most important antibiotic families used in veterinary medicines are ß-lactams (penicillins and cephalosporins), tetracyclines, chloramphenicols, macrolides, spectinomycin, lincosamide, sulphonamides, nitrofuranes, nitroimidazoles, trimethoprim, polymyxins, quinolones, and macrocyclics (glycopeptides, ansamycins, and aminoglycosides). Antibiotic residue presence is the main contributor to the development of antibiotic resistance, which is considered a chief concern for both human and animal health worldwide. The incorrect application and misuse of antibiotics carry the risk of the presence of residues in the edible tissues of the chicken, which can cause allergies and toxicity in hypersensitive consumers. The enforcement of the regulation of food safety depends on efficacious monitoring of antimicrobial residues in the foodstuff. In this review, we have explored the rapid detection of drug residues in broilers.

Carob (Ceratonia siliqua L.), Pharmacological and Phytochemical Activities of Neglected Legume of the Mediterranean Basin, as Functional Food.

Carob (Ceratonia siliqua L.) has been widely cultivated in different parts of the world, particularly in the Mediterranean region, and the tree belongs to the family Leguminosae. Several studies have indicated that carobs and their products can improve human health and help prevent different specific chronic diseases. Carob can considered as functional food due to its high content in dietary fibers, low-fat content, and high content of minerals. Its fruit is a pod containing 10%-20% seeds, and the pods consist of sugars, proteins, crude fibers, minerals, vitamins, polyphenols, vitamins, and lipids. In many countries in the Middle east, carob is mainly used to prepare as a traditional drink and some kinds of confectioneries. The powders can be utilized to prepare carob juice concentrate. The systematic review of documents from clinical trials and scientific societies dedicated to traditional medicine in China has been carried out. The goal of this review article is a survey of chemical compounds, and pharmaceutical benefits of carob, especially by considering traditional medicinal sciences. Moreover, clinical trials research promotes studies to highlight and focus on the scope of application of traditional medicinal science in the growing system of medicine.

The Roles of Plant-Growth-Promoting Rhizobacteria (PGPR)-Based Biostimulants for Agricultural Production Systems.

The application of biostimulants has been proven to be an advantageous tool and an appropriate form of management towards the effective use of natural resources, food security, and the beneficial effects on plant growth and yield. Plant-growth-promoting rhizobacteria (PGPR) are microbes connected with plant roots that can increase plant growth by different methods such as producing plant hormones and molecules to improve plant growth or providing increased mineral nutrition. They can colonize all ecological niches of roots to all stages of crop development, and they can affect plant growth and development directly by modulating plant hormone levels and enhancing nutrient acquisition such as of potassium, phosphorus, nitrogen, and essential minerals, or indirectly via reducing the inhibitory impacts of different pathogens in the forms of biocontrol parameters. Many plant-associated species such as Pseudomonas, Acinetobacter, Streptomyces, Serratia, Arthrobacter, and Rhodococcus can increase plant growth by improving plant disease resistance, synthesizing growth-stimulating plant hormones, and suppressing pathogenic microorganisms. The application of biostimulants is both an environmentally friendly practice and a promising method that can enhance the sustainability of horticultural and agricultural production systems as well as promote the quantity and quality of foods. They can also reduce the global dependence on hazardous agricultural chemicals. Science Direct, Google Scholar, Springer Link, CAB Direct, Scopus, Springer Link, Taylor and Francis, Web of Science, and Wiley Online Library were checked, and the search was conducted on all manuscript sections in accordance with the terms Acinetobacter, Arthrobacter, Enterobacter, Ochrobactrum, Pseudomonas, Rhodococcus, Serratia, Streptomyces, Biostimulants, Plant growth promoting rhizobactera, and Stenotrophomonas. The aim of this manuscript is to survey the effects of plant-growth-promoting rhizobacteria by presenting case studies and successful paradigms in various agricultural and horticultural crops.

Amino Acids Biostimulants and Protein Hydrolysates in Agricultural Sciences.

The effects of different types of biostimulants on crops include improving the visual quality of the final products, stimulating the immune systems of plants, inducing the biosynthesis of plant defensive biomolecules, removing heavy metals from contaminated soil, improving crop performance, reducing leaching, improving root development and seed germination, inducing tolerance to abiotic and biotic stressors, promoting crop establishment and increasing nutrient-use efficiency. Protein hydrolysates are mixtures of polypeptides and free amino acids resulting from enzymatic and chemical hydrolysis of agro-industrial protein by-products obtained from animal or plant origins, and they are able to alleviate environmental stress effects, improve growth, and promote crop productivity. Amino acids involve various advantages such as increased yield and yield components, increased nutrient assimilation and stress tolerance, and improved yield components and quality characteristics. They are generally achieved through chemical or enzymatic protein hydrolysis, with significant capabilities to influence the synthesis and activity of some enzymes, gene expression, and redox-homeostasis. Increased yield, yield components, and crop quality; improved and regulated oxidation-reduction process, photosynthesis, and physiological activities; decreased negative effects of toxic components; and improved anti-fungal activities of plants are just some of the more important benefits of the application of phenols and phenolic biostimulants. The aim of this manuscript is to survey the impacts of amino acids, different types of protein hydrolysates, phenols, and phenolic biostimulants on different plants by presenting case studies and successful paradigms in several horticultural and agricultural crops.

Enhancing Electrocatalytic CO2-to-CO Conversion by Weakening CO Binding through Nitrogen Integration in the Metallic Fe Catalyst.

Metallic iron (Fe) typically demonstrates the unfavorable catalytic activity for the CO2 reduction reaction (CO2RR), mainly attributed to the excessively strong binding of CO products on Fe sites. Toward this end, we employed an effective approach involving electronic structure modulation through nitrogen (N) integration to enhance the performance of the CO2RR. Here, an efficient catalyst has been developed, composed of N-doped metallic iron (Fe) nanoparticles encapsulated in a porous N-doped carbon framework. Notably, this N-integrated Fe catalyst displays significantly enhanced performance in the electrocatalytic reduction of CO2, yielding the highest CO Faradaic efficiency of 97.5% with a current density of 6.68 mA cm-2 at -0.7 V versus the reversible hydrogen electrode. The theoretical calculations, combined with the in situ attenuated total reflection surface-enhanced infrared absorption spectroscopy study, reveal that N integration modulates the electron density around Fe, resulting in the weakening of the binding strength between the Fe active sites and *CO intermediates, consequently promoting the desorption of CO and the overall CO2RR process.

Efficacy and safety of bexagliflozin compared with dapagliflozin as an adjunct to metformin in Chinese patients with type 2 diabetes mellitus: A 24-week, randomized, double-blind, active-controlled, phase 3 trial.

BACKGROUND: Bexagliflozin and dapagliflozin are sodium-glucose cotransporter-2 (SGLT2) inhibitors. No direct comparison of SGLT2 inhibitors in a randomized controlled trial has been reported to date. METHODS: This was a multicenter, randomized, double-blind, active-controlled trial comparing bexagliflozin to dapagliflozin for the treatment of type 2 diabetes mellitus in adults with disease inadequately controlled by metformin. Subjects (n = 406) were randomized to receive bexagliflozin (20 mg) or dapagliflozin (10 mg) plus metformin. The primary endpoint was noninferiority of bexagliflozin to dapagliflozin for the change in glycated hemoglobin (HbA1c) from baseline to week 24. Secondary endpoints included intergroup differences in fasting plasma glucose (FPG), 2-h-postprandial glucose (PPG), body weight, and systolic blood pressure (SBP) from baseline to week 24. The trial also evaluated the safety profiles. RESULTS: The model-adjusted mean change from baseline to week 24 HbA1c was -1.08% for bexagliflozin and -1.10% for dapagliflozin. The intergroup difference of 0.03% (95% confidence interval [CI] -0.14% to 0.19%) was below the prespecified margin of 0.4%, confirming the noninferiority of bexagliflozin. The changes from baseline in FPG, PPG, body weight, and SBP were -1.95 mmol/L, -3.24 mmol/L, -2.52 kg, and -6.4 mm Hg in the bexagliflozin arm and -1.87 mmol/L, -3.07 mmol/L, -2.22 kg, and -6.3 mm Hg in the dapagliflozin arm. Adverse events were experienced in 62.6% and 65.0% and serious adverse events affected 4.4% and 3.5% of subjects in the bexagliflozin and dapagliflozin arm, respectively. CONCLUSIONS: Bexagliflozin showed nearly identical effects and a similar safety profile to dapagliflozin when used in Chinese patients on metformin.

The Application of Arbuscular Mycorrhizal Fungi as Microbial Biostimulant, Sustainable Approaches in Modern Agriculture.

Biostimulant application can be considered an effective, practical, and sustainable nutritional crop supplementation and may lessen the environmental problems related to excessive fertilization. Biostimulants provide beneficial properties to plants by increasing plant metabolism, which promotes crop yield and improves the quality of crops; protecting plants against environmental stresses such as water shortage, soil salinization, and exposure to sub-optimal growth temperatures; and promoting plant growth via higher nutrient uptake. Other important benefits include promoting soil enzymatic and microbial activities, changing the architecture of roots, increasing the solubility and mobility of micronutrients, and enhancing the fertility of the soil, predominantly by nurturing the development of complementary soil microbes. Biostimulants are classified as microbial, such as arbuscular mycorrhizae fungi (AMF), plant-growth-promoting rhizobacteria (PGPR), non-pathogenic fungi, protozoa, and nematodes, or non-microbial, such as seaweed extract, phosphite, humic acid, other inorganic salts, chitin and chitosan derivatives, protein hydrolysates and free amino acids, and complex organic materials. Arbuscular mycorrhizal fungi are among the most prominent microbial biostimulants and have an important role in cultivating better, healthier, and more functional foods in sustainable agriculture. AMF assist plant nutrient and water acquisition; enhance plant stress tolerance against salinity, drought, and heavy metals; and reduce soil erosion. AMF are proven to be a sustainable and environmentally friendly source of crop supplements. The current manuscript gives many examples of the potential of biostimulants for the production of different crops. However, further studies are needed to better understand the effectiveness of different biostimulants in sustainable agriculture. The review focuses on how AMF application can overcome nutrient limitations typical of organic systems by improving nutrient availability, uptake, and assimilation, consequently reducing the gap between organic and conventional yields. The aim of this literature review is to survey the impacts of AMF by presenting case studies and successful paradigms in different crops as well as introducing the main mechanisms of action of the different biostimulant products.