S1 Site Research Articles

Foliar architecture differentially restrains metal sequestration capacity in wheat grains (Triticum aestivum L.) grown in hyper-chloride-contaminated soils.

Anthropogenic activities, such as industrial wastewater and use of water softeners, cause hyper-accumulation of Cl- in water sources and soils. Currently, industries have no sustainable method to remove these Cl- ions from wastewater. This study was conducted to evaluate the integrative responses of wheat cultivated in five industrial effluent-affected areas (S2-S6) by investigating soil characters and bioaccumulation of metals in wheat plants and grains. The S4 site (near the second chloride outlet) exhibited a higher concentration of CO2, SO2, NO2, Cl-, Cd, Mn, Ni, Cr, and Zn. Soil from S6 (sewage wastewater downstream getting mixed with chloride-contaminated water) had a minimum level of nutrients (Na, K, and Ca), maximum metals (Cd, Fe, Pb, Mn), and reduction in plant biomass. In site S2 (sewage wastewater upstream of the chloride factory), a higher level of minerals and metals was noted in the roots. Maximum metals in grains occurred in S6 with higher organic osmolytes. The sequestration capacity of metals in leaves was also increased by alterations in anatomical traits. Results indicated that metals and hyper-Cl- concentration employed a negative influence on the plants because of poor soil quality, extremely damaged microstructures leading to reduced yield, poor grain quality, and excessive translocation from roots to wheat grains. These findings revealed that contaminated plants used as either green forage or hay are noxious to animals and if used as grain for feed or humans can lead to serious health hazards.

Enhancement the electronic and optical properties of the T- graphene nanosheet in the present various impurities: DFT study

The electronic properties of the T-Greaphene nanosheet (T-GNS) are developed by using different concentrations of the Al and Si impurities. The results demonstrated the electronic band gap is reduced and the shape of the DOS is altered via utilizing various concentrations of Al and Si impurities, excepted the Al4Si4-doped T-GNS has an opposie thing. For the stability, we detected that the T-GNS became more stable and lower reactive due to the total energy is increased with these impurities. Moreover, the results have shown that the AlSi-doped T-GNS, Al2Si2-doped T-GNS, and Al4Si4-doped T-GNS have the anti-ferromagnetic properties. Also, the pristine T-GNS and AlSi-doped T-GNS have an open shell systems, which means there are spin up and spin down, respectively. Moreover, the nature bond is dictated by adding any impurity of Al and Si impurities. By using these impurities, the T-GNS become more solid due to it has a higher hardness, which required higher excitation energy to transfer electrons. For optical properties this study has discovered that all structures out of the visible light region. Moreover the λmax takes values from 1146.507 nm for Al2Si2-doped T-GNS in site (1)(s3) to 16,845.562 nm for Al4Si4-doped T-GNS (s1). Also, the excitation energy increased compared with T-GNS. In brief, the electronic and optical properties depend on the site and concentrations of Al and Si impurities.

The Effect of Heating on Properties of Sandy Soils

Although burning grass and crop residues is prohibited in many countries, farmers perceive it as a quick and inexpensive way to eliminate unwanted biomass. The aim of this study was to estimate the impact of heating temperature (simulation of biomass burning) on the studied properties (soil organic carbon (SOC) content, pH(H2O), water drop penetration time, WDPT, and contact angle, CA) of acidic sandy soils. Soil samples were taken from the experimental sites S1, S2, and S3 at Studienka village in the Borská nížina lowland (southwestern Slovakia). Experimental site S1 was arable land, experimental site S2 was arable land abandoned for approximately 10 years, and experimental site S3 was arable land abandoned for approximately 30 years with scattered Scots pine (Pinus sylvestris L.) trees. It was found that all the soil properties studied were strongly affected by heating. A drop in SOC was observed in all the soils for the heating temperature between 20 and 600 °C. Due to the incomplete combustion of SOC, a small (0.1–0.7%) SOC content was recorded even in soils heated to between 600 and 900 °C. An increase in pH(H2O) was observed in all the soils for the heating temperature higher than 300 °C. Soil from the experimental site S1 was wettable (WDPT < 5 s) for all of the heating temperatures. WDPT vs. heating temperature relationships for the soils from the experimental sites S2 and S3 were more complex. After a decrease in the heating temperature of 50 °C, an increase in WDPT for the heating temperature between 50 °C and 300 °C (for S3 soil) and 350 °C (for S2 soil) was registered. Finally, the WDPT dramatically dropped to 0 for the heating temperature of 350 °C (for S3 soil) and 400 °C (for S2 soil). CA started to decrease at 300 °C in all the soils and dropped to 0° for all the soils at 800 °C. CA > 0° measured in soils for the heating temperature between 400 and 800 °C, as a consequence of the small SOC contents due to the incomplete combustion of SOC, is a novelty of this study which demonstrates that CA is more sensitive to the changes in subcritical water repellency than WDPT.

Assessing surface water uses by water quality index: application of Qalyubia Governorate, Southeast Nile Delta, Egypt

In this study, water quality index (WQI) was applied at one of the most crowded Nile reaches surroundings in Egypt to investigate its impacts on different water uses. Twelve sites are selected for monitoring (S1–S12) within the irrigation system network of the Qalyubia Governorate, and water samples from these locations in 2021 were collected, analyzed, assessed, and compared to analyze water quality data collected in 2014 in light of the Egyptian permissible water quality limits regarding the drinking and irrigation uses. These two main sets of data were chosen to emphasize the change in WQI within this period, denoting the time before the epidemic COVID19 and after the lockdown of the epidemic in 2021 in the study area. Fifteen physicochemical water parameters were measured. The results show that the WQI for the surface water monitoring sites is classified as good quality except for S8, which showed a poor water quality type. In addition, S2 has recorded a BOD concentration of 6.4 mg/L, which is slightly above the Egyptian limit (6 mg/L). Also, S8 recorded a slight increase in Fe, Mn, and F compared to permissible concentrations. TDS varies between 258.08, 318, and (249 ± 18.2) mg/L for minimum, maximum, and average ± standard deviation, respectively, indicating suitable irrigation water. The study suggests that surface water can be used to irrigate crops, but it should be purified before being used for drinking purposes. A comparison of the water quality parameters for the years 2014 and 2021 for the sites S1, S4, S5, S7, S9, and S10 reveals an increase in water quality from poor (2014) to good (2021). Therefore, the poor water quality in 2014 can be referred the effect of inadequate sewage treatment, industrial wastewater flows, and urban runoff discharge, which had been decreased with the decrease in different activities during the epidemic period and lockdown.

Pollution profile, source identification, and risk assessments of persistent organic pollutants (POPs) and toxic elements in the sediments of one of the water supply areas (Sultanbahçedere lake) to Istanbul, Türkiye

This study was done to comprehensively exhibit the pollution level of surface sediments taken from Sultanbahçedere dam lake in terms of some persistent organic pollutants (POPs) and toxic elements, to decide the possible sources of polycyclic aromatic hydrocarbons (PAHs), to perform the ecological and human health risk assessments, and to evaluate the pollution profile with the hierarchically clustered heatmap (HCHM) analysis and principal component analysis (PCA). Naphthalene, Benzo(b)fluoranthene, Fluoranthene, Pyrene for PAHs; p,p-DDE, p,p-DDD, alpha-HCH, p,p-DDT, Endrin for OCPs; hexa and hepta chlorinated congeners accounting for 50.63% and 28.44% for polychlorinated biphenyls (PCBs); 1234678-HpCDD, OCDD for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs); PCB 118, PCB 105, PCB 167 for dioxin like-PCBs (DL-PCBs) and Al, Fe, Ca for elements were predominant in almost all of the sediments with a few exceptions. S4 site, which is one of the mid-sites of reservoir, has high concentrations in most of these pollutants. According to PAH diagnostic analysis, PAHs in the surface sediments are mostly affected by pyrogenic sources. The concentrations of POPs do not pose any toxic risk to aquatic organisms according to sediment quality guideline (SQG) and the limit values of other countries accepted in the world. Also, since none of the elements exceeded the effect range median (ERM) values, they do not pose a significant toxic risk to aquatic organisms. There is no risk for non-carcinogenic and carcinogenic hazards both for children and for adults considering hazard quotient (HQ), hazard index (HI), and lifetime cancer risk (LCR) values of all pollutants.

Dipeptidyl Peptidase IV Inhibitory Peptides from Chickpea Proteins (Cicer arietinum L.): Pharmacokinetics, Molecular Interactions, and Multi-Bioactivities.

Chickpea (Cicer arietinum L.) peptides can inhibit dipeptidyl peptidase IV (DPP-IV), an important type 2 diabetes mellitus therapeutic target. The molecular interactions between the inhibitory peptides and the active site of DPP-IV have not been thoroughly examined, nor have their pharmacokinetic properties. Therefore, the predictions of legumin- and provicilin-derived DPP-IV inhibitory peptides, their molecular interactions with the active site of DPP-IV, and their pharmacokinetic properties were carried out. Ninety-two unique DPP-IV inhibitory peptides were identified. Papain and trypsin were the enzymes with the highest AE (0.0927) and lowest BE (6.8625 × 10-7) values, respectively. Peptide binding energy values ranged from -5.2 to -7.9 kcal/mol. HIS-PHE was the most potent DPP-IV inhibitory peptide and interacts with residues of the active sites S1 (TYR662) and S2 (GLU205/ARG125 (hydrogen bonds: <3.0 Å)), S2 (GLU205/GLU206 (electrostatic interactions: <3.0 Å)), and S2' pocket (PHE357 (hydrophobic interaction: 4.36 Å)). Most peptides showed optimal absorption (76.09%), bioavailability (89.13%), and were non-toxic (97.8%) stable for gastrointestinal digestion (73.9%). Some peptides (60.86%) could also inhibit ACE-I. Chickpea is a source of non-toxic and bioavailable DPP-IV-inhibitory peptides with dual bioactivity. Studies addressing the potential of chickpea peptides as therapeutic or adjunct agents for treating type 2 diabetes are warranted.

Analysis and Evaluation of Concentrations of Potentially Toxic Elements in Landfills in the Araucanía Region, Chile

This preliminary study focuses on three abandoned sites, located in the communes of Temuco, Villarrica, and Lonquimay, in the Araucanía Region, Chile. Two of the sites were classified as illegal landfills and one was a former landfill. Seventy-three surface samples were taken, of which 32 were from site S1, 20 were from site S2, and 21 were from site S3. The objectives of this study were (1) to establish the background values of trace metals present in soils through different statistical methods, (2) to determine the level of contamination and possible ecological risks in soils, and (3) to assess the health risk posed to children and adults from potentially hazardous elements (As, Ba, Cd, Co, Cr, Cu, Hg, Ni, Pb, V, and Zn). The data analyzed belong to a report presented by Chile’s National Environmental Centre (CENMA). An evaluation was carried out through a multivariate statistical analysis to determine the type of origin and association of the trace elements, and spatial distribution maps were generated to establish the behavior of the contents of heavy metals present in the sites studied. The background values for sites S1, S2, and S3 were obtained by the median + 2MADdian absolute deviation) method. These values varied in the range of 14,702–41,785 mg kg−1 for Al, 0.83–8.9 mg kg−1 for As, 29.2–77.2 mg kg−1 for B, 59.2–143 mg kg−1 for Ba, 10.1–22.8 mg kg−1 for Cd, 18.4–51.2 mg kg−1 for Co, 12.3–38.0 mg kg−1 for Cr, 47.8–76.6 mg kg−1 for Cu, 36,230–64,274 mg kg−1 for Fe, 0.02–0.05 mg kg−1 for Hg, 482–4396 mg kg−1 for Mn, 16.7–19.3 mg kg−1 for Ni, 1.0–17.6 mg kg−1 for Pb, 1.4–28.2 mg kg−1 for Se, 108–258 mg kg−1 for V, and 68.1–145 mg kg−1 for Zn. In terms of ecological risk, the geoaccumulation index (Igeo), enrichment factor (EF), and contamination factor (Cf) values for As and Se at site S1, As at S2, and Pb with As at S3 were the main elements indicating the highest contamination levels, as well as a higher number of samples with contaminated content. The Potential Ecological Risk Index (PERI) revealed that on average, there was a moderate ecological risk for S1 and S2 and a considerable ecological risk for S3; the main contributions were generated by As and Hg in S1 and S2, while, in S3, they were produced by Pb and As. In terms of the risk to human health, the risk was higher in children than in adults, with the ingestion route as the main source of risk. For adults, it was found that there was no likelihood that they would develop any adverse non-carcinogenic or carcinogenic health effects. In contrast, children were found to be more likely to sustain adverse health effects. Regarding the non-carcinogenic risk to children, the Co and As samples at S1, S2, and S3, and the Pb at site S3 showed values exceeding the non-carcinogenic-risk limit. Regarding the carcinogenic risk, all three sites studied had Cd samples that indicated a likelihood of children developing cancer from this heavy metal.

Atomically Precise Copper Nanoclusters for Highly Efficient Electroreduction of CO2 towards Hydrocarbons via Breaking the Coordination Symmetry of Cu Site

AbstractWe propose an effective highest occupied d‐orbital modulation strategy engendered by breaking the coordination symmetry of sites in the atomically precise Cu nanocluster (NC) to switch the product of CO2 electroreduction from HCOOH/CO to higher‐valued hydrocarbons. An atomically well‐defined Cu6 NC with symmetry‐broken Cu−S2N1 active sites (named Cu6(MBD)6, MBD=2‐mercaptobenzimidazole) was designed and synthesized by a judicious choice of ligand containing both S and N coordination atoms. Different from the previously reported high HCOOH selectivity of Cu NCs with Cu−S3 sites, the Cu6(MBD)6 with Cu−S2N1 coordination structure shows a high Faradaic efficiency toward hydrocarbons of 65.5 % at −1.4 V versus the reversible hydrogen electrode (including 42.5 % CH4 and 23 % C2H4), with the hydrocarbons partial current density of −183.4 mA cm−2. Theoretical calculations reveal that the symmetry‐broken Cu−S2N1 sites can rearrange the Cu 3d orbitals with as the highest occupied d‐orbital, thus favoring the generation of key intermediate *COOH instead of *OCHO to favor *CO formation, followed by hydrogenation and/or C−C coupling to produce hydrocarbons. This is the first attempt to regulate the coordination mode of Cu atom in Cu NCs for hydrocarbons generation, and provides new inspiration for designing atomically precise NCs for efficient CO2RR towards highly‐valued products.

Quantifying cumulative changes in water quality caused by small floodgates in Taihu Lake Basin — A case in Wuxi

Small floodgates in the river network area own some characteristics: considerable quantity, wide range and short adjustment time, and intercepts the one-dimensional constant flow of rivers, which induce a great impact on riverine water quality. In this study, a typical urban floodgate-controlled reach was selected, and analyzed through the monthly data of four pollutant indicators TN, TP, CODMn and NH3-N at six sampling sites S1–S6 in 2016–2018. The principal component analysis and correlation analysis showed that TP was a representative indicator and there was a positive correlation between various pollutants. The difference test and linear regression showed that the concentration of pollutants at different sampling points varied greatly, and the pollutant concentrations in the longitudinal direction of the river showed a cubic-linear regression. The cluster system and CCME WQI showed that the water quality in the urban floodgate-controlled reach is “marginal” state, and TN and NH3-N are severely exceeding the standard. The “cumulative changes” of the floodgate on the pollutant input to the environment appeared spatial heterogeneity.

Genetically Encoded Crosslinking Enables Identification of Multivalent Ubiquitin-Deubiquitylating Enzyme Interactions.

Ubiquitin (Ub) proteoforms control nearly every aspect of eukaryotic cell biology through their diversity. Inspired by the widely used Ub C-terminal electrophiles (Ub-E), here we report the identification of multivalent binding of Ub with deubiquitylating enzymes (Dubs) using genetic code expansion (GCE) and crosslinking mass spectrometry. While the Ub-Es only gather structural information with the S1 Dub sites, we demonstrate that GCE of Ub with p-benzoyl-L-phenylalanine enables identification of interaction modes beyond the S1 site with a panel of Dubs of both eukaryotic and prokaryotic origin. Collectively, this represents the next generation of Ub-based affinity probes with a unique ability to unravel Ub interaction landscapes beyond what is afforded by cysteine-based chemistries.

Integrating Dual-Single-Atom Moieties with N, S Co-Coordination Configurations for Oxidative Cascaded Catalysis.

Oxidation reaction is of critical importance in chemical industry, in which the primary O2 activation step still calls for high-performance catalysts. Here, a newly developed precise locating carbonization strategy for the fabrication of 21 kinds of dual-metal single-atom catalysts with N, S co-coordinated configurations is reported. As is exemplified by CoN3 S1 /CuN4 @NC, systematical characterizations and in situ observations imply the atomic CoN3 S1 and CuN4 sites immobilized on N-doped carbon, over which the remarkable electron redistribution originating from their unsymmetrical coordination configurations. Impressively, the obtained CoN3 S1 /CuN4 @NC exhibits unprecedented capability in O2 activation and enables a spontaneous process through its dynamic configuration, significantly outperforming the CoN4 /CuN4 @NC and CoN3 S1 @NC counterparts. Hence, the CoN3 S1 /CuN4 @NC shows attractive performance in domino synthesis of natural flavone and 19 kinds of derivatives from benzyl alcohol, 2'-hydroxyacetophenone, and corresponding substituted substrates via aerobic oxidative coupling-dehydrogenation. Detailed reaction mechanisms and molecule behaviors over CoN3 S1 /CuN4 @NC are also investigated through in situ experiments and simulations.

A novel Greenness and Water Content Composite Index (GWCCI) for soybean mapping from single remotely sensed multispectral images

As a critical source of food and one of the most economically significant crops in the world, soybean plays an important role in achieving food security. Large area accurate mapping of soybean has long been a vital, but challenging issue in remote sensing, relying heavily on large-volume and representative training samples, whose collection is time-consuming and inefficient, especially for large areas (e.g., national scale). Thus, methods are needed that can map soybean automatically and accurately from single-date remotely sensed imagery. In this research, a novel Greenness and Water Content Composite Index (GWCCI) was proposed to map soybean from just a single Sentinel-2 multispectral image in an end-to-end manner without employing training samples. By capitalizing on the product of the NDVI (related to greenness) and the short-wave infrared (SWIR) band (related to canopy water content), the GWCCI provides the required information with which to discriminate between soybean and other land cover types. The effectiveness of the proposed GWCCI was investigated in seven typical soybean planting regions within four major soybean-producing countries across the world (i.e., China, the United States, Brazil and Argentina), with diverse climates, cropping systems and agricultural landscapes. In the experiments, an optimal threshold of 0.17 was estimated and adopted by the GWCCI in the first study site (S1) in 2021, and then generalised to the other study sites over multiple years for soybean mapping. The GWCCI method achieved a consistently higher accuracy in 2021 compared to two conventional comparative classifiers (support vector machine (SVM) and random forest (RF)), with an average overall accuracy (OA) of 88.30% and a Kappa coefficient (k) of 0.77; significantly greater than those of RF (OA: 80.92%, k: 0.62) and SVM (OA: 80.29%, k: 0.60). Furthermore, the OA of the extended years was highly consistent with that of 2021 for study sites S2 to S7, demonstrating the great generalisation capability and robustness of the proposed approach over multiple years. The proposed GWCCI method is straightforward, reliable and robust, and represents an important step forward for mapping soybean, one of the most significant crops grown globally.

Exploring unbinding mechanism of drugs from SERT via molecular dynamics simulation and its implication in antidepressants

The human serotonin transporter (SERT) terminates neurotransmission by removing serotonin from the synaptic cleft, which is an essential process that plays an important role in depression. In addition to natural substrate serotonin, SERT is also the target of the abused drug cocaine and, clinically used antidepressants, escitalopram, and paroxetine. To date, few studies have attempted to investigate the unbinding mechanism underlying the orthosteric and allosteric modulation of SERT. In this article, the conserved property of the orthosteric and allosteric sites (S1 and S2) of SERT was revealed by combining the high resolutions of x-ray crystal structures and molecular dynamics (MD) simulations. The residues Tyr95 and Ser438 located within the S1 site, and Arg104 located within the S2 site in SERT illustrate conserved interactions (hydrogen bonds and hydrophobic interactions), as responses to selective serotonin reuptake inhibitors. Van der Waals interactions were keys to designing effective drugs inhibiting SERT and further, electrostatic interactions highlighted escitalopram as a potent antidepressant. We found that cocaine, escitalopram, and paroxetine, whether the S1 site or the S2 site, were more competitive. According to this potential of mean force (PMF) simulations, the new insights reveal the principles of competitive inhibitors that lengths of trails from central SERT to an opening were ∼18 Å for serotonin and ∼22 Å for the above-mentioned three drugs. Furthermore, the distance between the natural substrate serotonin and cocaine (or escitalopram) at the allosteric site was ∼3 Å. Thus, it can be inferred that the potent antidepressants tended to bind at deeper positions of the S1 or the S2 site of SERT in comparison to the substrate. Continuing exploring the processes of unbinding four ligands against the two target pockets of SERT, this study observed a broad pathway in which serotonin, cocaine, escitalopram (at the S1 site), and paroxetine all were pulled out to an opening between MT1b and MT6a, which may be helpful to understand the dissociation mechanism of antidepressants.

Hydrogeochemical Evaluation of Groundwater for Drinking and Irrigation Purposes in the Upper Piedmont Area of Haridwar, India

In this study, the suitability of groundwater quality for the purpose of drinking and irrigation was evaluated in the upper piedmont area of Haridwar, India. In this regard, inverse distance-weighted interpolation, water quality index (WQI), principal component analysis (PCA), piper trilinear diagram (PTD) analysis, and sodium absorption ratio (SAR) methods were used to assess the geospatial variation of groundwater quality. The results showed that groundwater was partially affected by rapid industrialization and urbanization practices. The groundwater quality revealed the presence of different cations and anions in the following order: Ca2+ > Na+ > Mg2+ > K+ and HCO3– > NO3– > SO42– > Cl– > SiO2– > F–. WQI showed an excellent range (29.94–45.17) for sampling sites S1–S3 and S5–S8 and a good value for site S4 (99.2). In addition, PTD confirmed that the calcium and magnesium bicarbonate type and mixed type for groundwater while PCA revealed that nitrate was dominant at site S4. In addition, the SAR and Na contents were in excellent ranges, indicating their suitability for irrigation purposes. The outcomes of this study indicated that geogenic and anthropogenic processes were the major reasons for the change in groundwater quality of this region.

Status of potentially toxic metal pollution in the agricultural soils near to India’s largest chromite mine

This study highlights the contamination of potentially toxic elements (PTEs-- Cd, Cr, Fe, Ni, Pb, Mn, and Zn) in five agricultural sites near to the Sukinda chromite mine, at Odisha, in India. The results indicated that Fe and Cr had very high concentration 5758–12687 mg kg−1 and 2144–5588 mg kg−1 respectively, followed by the concentrations of Ni, Mn, Zn, and Cd. The geoaccumulation study indicated ‘moderately to heavily contaminated’ with Cr in all the studied sites while ‘high to extremely high’ Cd concentration in the sites S1, S3, and S5. The ecological Risk Index also indicated few study sites have‘ considerable to very high potential risk’ due to PTEs concentration, which is concerning for agriculture, food security, and human health for the sustainable future. This pilot scale study proposes policy-level interventions to address the PTEs pollution in this region.

Discovery of a Novel Series of Potent, Selective, Orally Available, and Brain-Penetrable C1s Inhibitors for Modulation of the Complement Pathway.

A novel series of non-amidine-based C1s inhibitors have been explored. Starting from high-throughput screening hit 3, isoquinoline was replaced with 1-aminophthalazine to enhance C1s inhibitory activity while exhibiting good selectivity against other serine proteases. We first disclose a crystal structure of a complex of C1s and a small-molecule inhibitor (4e), which guided structure-based optimization around the S2 and S3 sites to further enhance C1s inhibitory activity by over 300-fold. Improvement of membrane permeability by incorporation of fluorine at the 8-position of 1-aminophthalazine led to identification of (R)-8 as a potent, selective, orally available, and brain-penetrable C1s inhibitor. (R)-8 significantly inhibited membrane attack complex formation induced by human serum in a dose-dependent manner in an in vitro assay system, proving that selective C1s inhibition blocked the classical complement pathway effectively. As a result, (R)-8 emerged as a valuable tool compound for both in vitro and in vivo assessment.

Polymorphism in LiDy(WO4)2: Phase tunable synthesis, neutron diffraction, and symmetry-driven upconversion red emission

Tunable polymorphic structures to achieve novel properties are of great concern for energy-related applications. Herein, we demonstrate temperature-driven irreversible structural phase transition in LiDy(WO4)2 (β-LiDyW and α-LiDyW). A facile sol-gel method has been employed to achieve phase pure crystalline polymorphs at relatively lower temperatures and time. LiDy(WO4)2 crystallizes in a monoclinic wolframite-type structure (space group, P21/n, No = 14) at ambient temperature and a Scheelite-like tetragonal structure (space group, I41/a, No = 88) upon heating at high temperature. Crystal structure analysis shows that Li+ and Dy3+ occupy the distinct site, and W forms a distorted WO6 octahedron in the β-LiDyW phase. In contrast, Li+ and Dy3+ are statistically distributed on a dodecahedral S4 site sharing a similar crystallographic lattice site, and W forms a WO4 tetrahedron in the α-LiDyW phase. The Wolframite to Scheelite (β → α) transformation is due to the increase in the crystal symmetry on the heating function where distorted WO6 transformed to free WO4 going from β → α phase and coordination of W+6 is lowered. Density functional theory calculations at 0 K revealed that the β-LiDyW is energetically more favorable than α-LiDyW by 337.3 meV per formula unit. The co-substitution of the Yb3+−Er3+ pair in LiDy(WO4)2 lattice displays a concentration-dependent upconversion red emission when excited with 980 nm. The monoclinic phase of LiDy0.7Yb0.2Er0.1(WO4)2 shows an intense red emission at 656 nm due to inherent lower crystal symmetry. Distorted WO6 and chemically induced lattice distortions in β-LiDy0.7Yb0.2Er0.1(WO4)2 would have strongly influenced the coordination environment of the Er3+ to achieve red emission. This study presents the structural relationship among the tunable crystallographic phases of LiDy(WO4)2 with the observed red emission induced by Yb3+−Er3 upon 980 nm irradiation.

Structure-based virtual screening for potent inhibitors of GH-20 β-N-acetylglucosaminidase: Classical and machine learning scoring functions, and molecular dynamics simulations

GH-20 β-N-acetylglucosaminidases (GlcNAcases) are promising targets in the development of antimicrobial agents against Vibrio infections in humans and aquatic animals. In this study, we set up structure-based virtual screening to identify potential GH-20 GlcNAcase inhibitors from the Reaxys commercial database, using VhGlcNAcase from V. campbellii type strain ATCC® BAA 1116 as the protein target and Redoxal as the reference ligand. Using ChemPLP and RF-Score-VS machine learning scoring functions, eight lead compounds were identified and further evaluated for protein interaction preference and pharmacological properties. Protein-ligand analysis demonstrated that all selected compounds interacted exclusively at subsite − 1 with five hydrophobic residues W487, W505, W546, W582 and V544 at site S1, and with two polar residues, D437 and E438, at site 3. For subsite + 1, the most common residues were R274 and E584 at site 2 and I397 and Q398 at site 4. Based on the data obtained from binding free energy changes (ΔG°binding), pharmacological property analysis and molecular dynamic simulations, two ChemPLP compounds, 338175 and 1146525, and one RF-Score-VS compound, 337447, were considered as the likely lead compounds. The most promising compound, 1146525, could serve as a scaffold for the future design of novel antimicrobial agents against Vibrio infections.

The inhibitory effect of vitamin D on myocardial homocysteine levels involves activation of Nrf2-mediated methionine synthase

BackgroundHomocysteine (Hcy) is a synthetic amino acid containing sulfhydryl group, which is an intermediate product of the deep metabolic pathway of methionine and cysteine. The abnormal increase in fasting plasma total Hcy concentration caused by various factors is called hyperhomocysteine (HHcy). HHcy is closely relevant to the occurrence and progression of diverse cardiovascular and cerebrovascular diseases, such as coronary heart disease, hypertension and diabetes, etc. Vitamin D/vitamin D receptor (VDR) pathway is pointed out that prevent cardiovascular disease by reducing serum homocysteine levels. Our research is designed to explore the potential mechanism of vitamin D in the prevention and treatment of HHcy. Methods and resultsThe Hcy and 25(OH)D3 levels in mouse myocardial tissue, serum or myocardial cells were detected using ELISA kits. The expression levels of VDR, Nrf2 and methionine synthase (MTR) were observed using Western blotting, immunohistochemistry and real time polymerase chain reaction (PCR). General information of the mice, including diet, water intake and body weight, was recorded. Vitamin D up-regulated the mRNA and protein expression of Nrf2 and MTR in mouse myocardial tissue and cells. CHIP assay determined that the combination of Nrf2 binding to the S1 site of the MTR promoter in cardiomyocytes using traditional PCR and real time PCR. Dual Luciferase Assay was applied to detect the transcriptional control of Nrf2 on MTR. The up-regulation effect of Nrf2 on MTR was verified by Nrf2 knockout and overexpression in cardiomyocytes. The role of Nrf2 in vitamin D inhibition of Hcy was revealed using Nrf2-knockdown HL-1 cells and Nrf2 heterozygous mice. Western blotting, real time PCR, IHC staining and ELISA showed that Nrf2 deficiency could restrain the increase in MTR expression and the decrease in Hcy level induced by vitamin D. The transcriptional activities of Nrf2/MTR were activated by vitamin D/VDR with a decrease in Hcy. ConclusionVitamin D/VDR upregulates MTR in an Nrf2-dependent manner, thereby reducing the risk of HHcy.

A Critical Study on Acylating and Covalent Reversible Fragment Inhibitors of SARS-CoV-2 Main Protease Targeting the S1 Site with Pyridine.

SARS coronavirus main proteases (3CL proteases) have been validated as pharmacological targets for the treatment of coronavirus infections. Current inhibitors of SARS main protease, including the clinically admitted drug nirmatrelvir are peptidomimetics with the downsides of this class of drugs including limited oral bioavailability, cellular permeability, and rapid metabolic degradation. Here, we investigate covalent fragment inhibitors of SARS Mpro as potential alternatives to peptidomimetic inhibitors in use today. Starting from inhibitors acylating the enzyme's active site, a set of reactive fragments was synthesized, and the inhibitory potency was correlated with the chemical stability of the inhibitors and the kinetic stability of the covalent enzyme-inhibitor complex. We found that all tested acylating carboxylates, several of them published prominently, were hydrolyzed in assay buffer and the inhibitory acyl-enzyme complexes were rapidly degraded leading to the irreversible inactivation of these drugs. Acylating carbonates were found to be more stable than acylating carboxylates, however, were inactive in infected cells. Finally, reversibly covalent fragments were investigated as chemically stable SARS CoV-2 inhibitors. Best was a pyridine-aldehyde fragment with an IC50 of 1.8 μM at a molecular weight of 211 g/mol, showing that pyridine fragments indeed are able to block the active site of SARS-CoV-2 main protease.