Signatures of Adaptation and Purifying Selection in Highland Populations of Dasiphora fruticosa.

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.

Cryo-electron microscopy structure and translocation mechanism of the crenarchaeal ribosome.

Archaeal ribosomes have many domain-specific features; however, our understanding of these structures is limited. We present 10 cryo-electron microscopy (cryo-EM) structures of the archaeal ribosome from crenarchaeota Sulfolobus acidocaldarius (Sac) at 2.7-5.7 Å resolution. We observed unstable conformations of H68 and h44 of ribosomal RNA (rRNA) in the subunit structures, which may interfere with subunit association. These subunit structures provided models for 12 rRNA expansion segments and 3 novel r-proteins. Furthermore, the 50S-aRF1 complex structure showed the unique domain orientation of aRF1, possibly explaining P-site transfer RNA (tRNA) release after translation termination. Sac 70S complexes were captured in seven distinct steps of the tRNA translocation reaction, confirming conserved structural features during archaeal ribosome translocation. In aEF2-engaged 70S ribosome complexes, 3D classification of cryo-EM data based on 30S head domain identified two new translocation intermediates with 30S head domain tilted 5-6° enabling its disengagement from the translocated tRNA and its release post-translocation. Additionally, we observed conformational changes to aEF2 during ribosome binding and switching from three different states. Our structural and biochemical data provide new insights into archaeal translation and ribosome translocation.

Archaeal ribosomes display variations in their ribosomal proteins and ribosomal RNA (rRNA) expansion segments (ESs). Protein translation in archaea combines features in both bacterial and eukaryotic translation. In this study, we present 10 cryo-electron microscopy structures of the archaeal ribosome from crenarchaeota Sulfolobus acidocaldarius (Sac). The 50S and 30S subunit structures present 3 novel ribosomal proteins and 12 rRNA ESs. The 70S Sac ribosome structures were captured in seven distinct functional states, including pre-, intermediate- and post-translocation states. Specifically, we identified two novel translocation intermediates, in which the 30S subunit head domain tilts outward to release the translocated P-site transfer RNA. The structures of archaeal ribosomes provide insights into the archaeal translation and ribosome translocation.

The structural basis for inhibition of ribosomal translocation by viomycin.

Viomycin, an antibiotic that has been used to fight tuberculosis infections, is believed to block the translocation step of protein synthesis by inhibiting ribosomal subunit dissociation and trapping the ribosome in an intermediate state of intersubunit rotation. The mechanism by which viomycin stabilizes this state remains unexplained. To address this, we have determined cryo-EM and X-ray crystal structures of Escherichia coli 70S ribosome complexes trapped in a rotated state by viomycin. The 3.8-Å resolution cryo-EM structure reveals a ribosome trapped in the hybrid state with 8.6° intersubunit rotation and 5.3° rotation of the 30S subunit head domain, bearing a single P/E state transfer RNA (tRNA). We identify five different binding sites for viomycin, four of which have not been previously described. To resolve the details of their binding interactions, we solved the 3.1-Å crystal structure of a viomycin-bound ribosome complex, revealing that all five viomycins bind to ribosomal RNA. One of these (Vio1) corresponds to the single viomycin that was previously identified in a complex with a nonrotated classical-state ribosome. Three of the newly observed binding sites (Vio3, Vio4, and Vio5) are clustered at intersubunit bridges, consistent with the ability of viomycin to inhibit subunit dissociation. We propose that one or more of these same three viomycins induce intersubunit rotation by selectively binding the rotated state of the ribosome at dynamic elements of 16S and 23S rRNA, thus, blocking conformational changes associated with molecular movements that are required for translocation.

In vivo antibacterial activity of medicinal plant Sophora flavescens against Streptococcus agalactiae infection.

Streptococcosis disease caused by Streptococcus agalactiae (Group B Streptococcus, GBS) results in a huge economic loss of tilapia culture. It is urgent to find new antimicrobial agents against streptococcosis. In this study, 20 medicinal plants were evaluated in vitro and in vivo to obtain medicinal plants and potential bioactive compounds against GBS infection. The results showed that the ethanol extracts of 20 medicinal plants had low or no antibacterial properties in vitro, with a minimal inhibitory concentration ≥256 mg/L. Interestingly, in vivo tests showed that 7 medicinal plants could significantly inhibit GBS infection in tilapia, and Sophora flavescens (SF) had the strongest anti-GBS activity in tilapia, reaching 92.68%. SF could significantly reduce the bacterial loads of GBS in different tissues (liver, spleen and brain) of tilapia after treated with different tested concentrations (12.5, 25.0, 50.0 and 100.0 mg/kg) for 24 h. Moreover, 50 mg/kg SF could significantly improve the survival rate of GBS-infected tilapia by inhibiting GBS replication. Furthermore, the expression of antioxidant gene cat, immune-related gene c-type lysozyme and anti-inflammatory cytokine il-10 in liver tissue of GBS-infected tilapia significantly increased after treated with SF for 24 h. Meanwhile, SF significantly reduced the expression of immune-related gene myd88 and pro-inflammatory cytokines il-8 and il-1ß in liver tissue of GBS-infected tilapia. The negative and positive models of UPLC-QE-MS, respectively, identified 27 and 57 components of SF. The major components of SF extract in the negative model were α, α-trehalose, DL-malic acid, D- (-)-fructose and xanthohumol, while in the positive model were oxymatrine, formononetin, (-)-maackiain and xanthohumol. Interestingly, oxymatrine and xanthohumol could significantly inhibit GBS infection in tilapia. Taken together, these results suggest that SF can inhibit GBS infection in tilapia, and it has potential for the development of anti-GBS agents.

Natural component geniposide enhances survival rate of crayfish Procambarus clarkii infected with white spot syndrome virus.

White Spot Disease (WSD), caused by white spot syndrome virus (WSSV), is an acute and highly lethal viral disease of shrimp. Currently, there are no commercially available drugs to control WSD. It is urgent and necessary to find anti-WSSV drugs. Natural compounds are an important source of antiviral drug discovery. In this study, the anti-WSSV activity of natural compound geniposide (GP) was investigated in crayfish Procambarus clarkii. Results showed that GP had a concentration-dependent inhibitory effect on WSSV replication in crayfish at 24 h, and highest inhibition was more than 98%. In addition, GP significantly inhibited the expression of WSSV immediate-early gene ie1, early gene DNApol, late gene VP28. The mortality of WSSV-infected crayfish in control groups was 100%, while it reduced by 70.0% when treated with 50 mg/kg GP. Co-incubation, pre-treatment and post-treatment experiments showed that GP could prevent and treat WSSV infection in crayfish by significantly inhibiting WSSV multiplication. Mechanistically, the syntheses of WSSV structural proteins VP19, VP24, VP26 and VP28 were significantly inhibited by GP in S2 cells. Furthermore, GP could also suppress WSSV replication by blocking the expression of antiviral immunity-related factor STAT to reduce ie1 transcription. Moreover, GP possessed anti-inflammatory and anti-oxidative activity in crayfish. Overall, GP has the potential to be developed as a preventive or therapeutic agent against WSSV infection.

Natural component plumbagin as a potential antibacterial agent against Streptococcus agalactiae infection.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), can infect humans, terrestrial animals and fish. The emergence of bacterial resistance of S. agalactiae to antibiotics leads to an urgent need of exploration of new antimicrobial agents. In the study, the antibacterial activity of natural component plumbagin (PLB) against S. agalactiae was investigated in vitro and in vivo. The results showed that the minimal inhibitory concentration (MIC) of PLB against S. agalactiae was 8 mg/L. The growth curve assay revealed that PLB could inhibit the growth of S. agalactiae. In addition, the time-killing curve showed that S. agalactiae was killed almost completely by 2-fold MIC of PLB within 12 h. Transmission electron microscopy results showed obvious severe morphological destruction and abnormal cells of S. agalactiae after treated with PLB. The pathogenicity of S. agalactiae to zebrafish was significantly decreased after preincubation with PLB for 2 h in vitro, further indicating the bactericidal activity of PLB. Interestingly, PLB could kill S. agalactiae without inducing resistance development. Furthermore, pretreatment and post-treatment assays suggested that PLB also exhibited the antibacterial activity against S. agalactiae infection in vivo by effectively reducing the bacterial load and improving the survival rate of S. agalactiae-infected zebrafish. In summary, PLB had potent antibacterial activity against S. agalactiae in vitro and in vivo, and it could be an excellent antimicrobial candidate to prevent and control S. agalactiae infection.

Structural and dynamic characterization of the C-terminal tail of ErbB2: Disordered but not random.

ErbB2 (or HER2) is a receptor tyrosine kinase overexpressed in some breast cancers and associated with poor prognosis. Treatments targeting the receptor extracellular and kinase domains have greatly improved disease outcome in the last 20 years. In parallel, the structures of these domains have been described, enabling better mechanistic understanding of the receptor function and targeted inhibition. However, the ErbB2 disordered C-terminal cytoplasmic tail (CtErbB2) remains very poorly characterized in terms of structure, dynamics, and detailed functional mechanism. Yet, it is where signal transduction is triggered via phosphorylation of tyrosine residues and carried out via interaction with adaptor proteins. Here, we report the first description, to our knowledge, of the ErbB2 disordered tail at atomic resolution using NMR, complemented by small-angle x-ray scattering. We show that although no part of CtErbB2 has any fully populated secondary or tertiary structure, it contains several transient α-helices and numerous transient polyproline II helices, populated up to 20 and 40%, respectively, and low but significant compaction. The presence of some structural elements suggests, along the lines of the results obtained for EGFR (ErbB1), that they may have a functional role in ErbB2's autoregulation processes. In addition, the transient formation of polyproline II helices is compliant with previously suggested interactions with SH3 domains. All in all, our in-depth structural study opens perspectives in the mechanistic understanding of ErbB2.

Automated µFTIR Imaging Demonstrates Taxon-Specific and Selective Uptake of Microplastic by Freshwater Invertebrates.

Microplastic particles can be deposited to sediments and subsequently ingested by benthic organisms. It is unknown to what extent ingestion of microplastic is taxon-specific or whether taxa can be selective toward certain types of microplastics. Here, we used state-of-the-art automated micro-Fourier-transform infrared (µFTIR) imaging and attenuated total reflectance FTIR spectroscopy to determine small-size (20-500 µm) and large-size (500-5000 µm) microplastic particles in sediments and a range of benthic invertebrate species sampled simultaneously from the Dommel River in the Netherlands. Microplastic number concentrations differed across taxa at the same locations, demonstrating taxon-specific uptake, whereas size distributions were the same across sediments and taxa. At the site with the highest concentration, microplastic occupied up to 4.0% of the gut volume of Asellidae. Particle shape distributions were often not statistically different between sediments and taxa, except for Astacidea at one of the locations where the proportion of particles with a length to width ratio >3 (i.e., fibers) was twice as high in sediments than in Astacidea. Acrylates/polyurethane/varnish was predominately found in sediments, while soft and rubbery polymers ethylene propylene diene monomer and polyethylene-chlorinated were the dominant polymers found in invertebrates. Microplastic polymer composition and thus polymer density differed significantly between invertebrates and their host sediment. Trophic transfer at the base of the food web appears to have a filter function with respect to microplastic particle types and shapes. Together with the very high ingestion rates, this has clear implications for ecological and human health risks, where uptake concerns edible species (e.g., Astacidea).

Distribution, partitioning behavior and potential source of legacy and alternative per- and polyfluoroalkyl substances (PFASs) in water and sediments from a subtropical Gulf, South China Sea.

Legacy per- and polyfluoroalkyl acids (PFASs) have received global concern over the scientific and public community since this century. However, the information on alternative PFASs pollution in the marine environment, especially in the subtropical marine environment is extremely limited. This study investigated the occurrence, partitioning, potential sources, and ecological risks of PFASs, including perfluoroalkane sulfonic acids (PFSAs), perfluoroalkyl carboxylic acids (PFCAs), and alternative PFASs, in surface water and sediments from the subtropical Beibu Gulf, South China. Concentrations of total PFASs (∑PFASs) were in the range of 0.98-2.64 ng/L in water and 0.19-0.66 ng/g (dry weight, dw) in sediment, respectively. Perfluorooctanoic acid (PFOA) was the most abundant PFAS in water, while PFASs in sediment were dominated by perfluorooctanesulfonic acid (PFOS) and PFOA. Among investigated environmental parameters (total organic carbon (TOC), grain size, water pH, sediment pH, and salinity), TOC and salinity were the dominant factors influencing the sediment-water distribution coefficient (Kd) of PFOA, perfluorodecanoic acid (PFDA), and perfluorononanoic acid (PFNA). Log Kd and log soil organic carbon-water distribution coefficient (Koc) both increase with increasing carbon chain length of PFASs. Significantly positive correlations between PFOS and perfluorohexanoic acid (PFHxA) (p < 0.05), PFOA and perfluoro-1-butane-sulfonamide (FBSA) were observed, suggesting that these PFASs might have similar sources and transport routes. Preliminary environmental risk assessment showed that PFOA and PFOS would not pose risks to the marine aquatic environment. This is the first comprehensive survey of legacy and alternative PFASs in a subtropical area of the Beibu Gulf, which provides significant data and scientific basis to better understand the fate of PFASs and pollution control management.

Diagnostic efficacy of CBCT, MRI, and CBCT-MRI fused images in distinguishing articular disc calcification from loose body of temporomandibular joint.

OBJECTIVES: To evaluate the diagnostic efficacy of CBCT-MRI fused images for articular disc calcification of temporomandibular joint (TMJ). MATERIALS AND METHODS: Twenty patients (24 TMJs) whose image examinations showed dense bodies in the TMJ space were included in the study. The locations of dense bodies evaluated by the three experts were used as a reference standard. Three oral and maxillofacial radiology residents evaluated whether the dense bodies were disc calcification or not, with a five-point scale for four sets of images (CBCT alone, MRI alone, both CBCT and MRI observed at a time, and CBCT-MRI fused images) randomly and independently. Each set of images was observed at least 1 week apart. A second evaluation was performed after 4 weeks. Intraclass correlation coefficients were calculated to assess the intra- and inter-observer agreement. The areas under the ROC curves (AUCs) were compared between the four image sets using Z test. RESULTS: Ten cases were determined as articular disc calcifications, and fourteen cases were recognized as loose bodies in the TMJ spaces. The average AUC index for the CBCT-MRI fused images was 0.95 and significantly higher than the other sets (p < 0.01). The intra- and inter-observer agreement in the CBCT-MRI fused images (0.90-0.91, 0.93) was excellent and higher than those in the other images. CONCLUSIONS: CBCT-MRI fused images can significantly improve the observers' reliability and accuracy in determining articular disc calcification of the TMJ. CLINICAL RELEVANCE: The multimodality image fusion is feasible in detecting articular disc calcification of the TMJ which are hard to define by CBCT or MRI alone. It can be utilized especially for inexperienced residents to shorten the learning curve and improve diagnostic accuracy.

Identification of Common Sarcosaprophagous Flies in the Yangtze River Delta by COâ Gene. / 利用COâ åŸºå› é‰´åˆ«é•¿ä¸‰è§’åœ°åŒºå¸¸è§å—œå°¸æ€§è‡ç±».

OBJECTIVES: To identify the common sarcosaprophagous flies in the Yangtze River Delta based on mitochondrial cytochrome c oxidase subunit Ⅰ(COⅠ) gene sequence and verify the reliability of this method. METHODS: Seven common genetically stable sarcosaprophagous flies in three families and six genera were collected from large domestic pig carcasses placed in the field and cultured in the laboratory for many generations. The whole genome DNA was extracted and the COⅠ gene fragment was amplified. The forward and reverse sequencing was followed by splicing. The base composition of the amplified fragment and the rate of interspecific evolutionary divergence were analyzed by software such as Mega 7.0.26. The phylogenetic tree of COⅠ gene sequence of common necrophagous flies in the Yangtze River Delta was established by neighbor joining (NJ) method and unweighted pair-group method with arithmetic means (UPGMA) method. RESULTS: The average base composition of different flies was A(30.14%), T(38.23%), C(15.98%), G(15.65%). The rate of interspecific evolutionary divergence ranged from 2.2% to 15.3%, the lowest rate was between Chrysomya megacephala and Chrysomya pinguis, the highest rate was between Muscina stabulans and Boettcherisca peregrina. CONCLUSIONS: COⅠ gene can be used to identify the common necrophagous flies in the Yangtze River Delta.

Research Progress on Developmental Biology of Sarcosaprophagous Insects. / å—œå°¸æ€§æ˜†è™«å‘è‚²ç”Ÿç‰©å­¦ç ”ç©¶è¿›å±•.

Forensic entomology provides a feasible way to estimate postmortem interval (PMI), of which the growth and development of sarcosaprophagous insects is the most widely used indicator in forensic practice. Over the years, forensic entomologists have carried out a large number of studies on the development biology of sarcosaprophagous insects. This paper illustrates the main factors that affect the development of sarcosaprophagous insects, including temperature, humidity, light, food types and poisons. The development indicators of sarcosaprophagous insects were reviewed from the perspectives of morphology, differential gene expression and biochemical characteristics. It is emphasized that future research of development biology on sarcosaprophagous insects should fully absorb and integrate the methods of artificial intelligence and omics, and the research object also needs further expansion in order to establish a more objective and more accurate PMI estimation method.

Poly (I:C) alleviates obesity related pro-inflammatory status and promotes glucose homeostasis.

Obesity associated insulin resistance (IR) is implicated in chronic inflammation that mediated by the immune system. Imbalance between anti-inflammatory and pro-inflammatory response contributes to the origins and drivers of IR. However, cells of innate and adaptive immune system participate in the pathogenesis of IR, while glucose homeostasis related immune tolerance could be compromised high fat diet (HFD) reduced metabolic disorder. Although previous studies have demonstrated that anti-inflammatory therapy has a protective role in alleviating the pro-inflammatory status in HFD induced IR, the precise mechanism is still unclear. Ploy (I:C) is a synthetic double-stranded RNA that activates innate and/or adaptive immune response via retinoic acid-inducible gene-I (RIG-I), toll-like receptor 3 (TLR3) and melanoma differentiation-associated protein 5 (MDA5). In the present study, we initially perform a novel research on the relationship between Poly (I:C) preconditioning and improved glucose metabolism in obesity related IR. Interestingly, Poly (I:C) treatment has alleviated the pro-inflammatory status and promoted glucose homeostasis during a HFD feeding. Improved insulin sensitivity is consistent with enhanced immune tolerance, which accompanied with increased Foxp3+ regulatory T cells (Tregs). Of note, Tregs have a pivotal role in orchestrating the self-balance between autoimmunity and inflammation reaction. Thus, our findings reveal that Ploy (I:C) preconditioning prevents HFD induced glucose intolerance, which may be recognized as vaccination by the host. Overall, selectively targeting precise immune regulators may lead to new classes of potentially meaningful therapies for IR in the clinical trials.

Population pharmacokinetic models of lamotrigine in different age groups of Chinese children with epilepsy.

PURPOSE: The study aims to establish population pharmacokinetic (PPK) models of lamotrigine (LTG) in different age groups of epileptic children by nonlinear mixed effect modelling(NONMEM), and provide essential tools and theoretical basis for individualised optimal drug dose. METHODS: Cases of 473 epileptic children were divided into infant, toddler and preschool age (≤6 years) (n = 211), school age (6-12 years) (n = 171) and adolescence age (>12 years) (n = 81). A total of 625 steady-state serum trough concentration samples were extracted. The clinical information included demography, medication, serum concentration data and blood biochemical parameters. PPK models of LTG were established by NONMEM program, using first-order absorption and elimination. Demography and drug combination was investigated for influence on apparent clearance (CL) and apparent volume of distribution (Vd). To assess the accuracy and precision of the different ages and whole-age model, the mean prediction error (MPE), mean absolute error (MAE) and root mean squared error (RMSE) were compared. RESULTS: The final model of LTG in different ages stage and whole age was as follows: (1) infant, toddler and preschool age CL = 0.715 × [(WEIG/16.25)0.655] × (0.458VPA) × (1.99IND), V = 10.4; (2) school age CL(L/h) = 1.01 × (WEIG/30)0.399 × 0.465VPA × 1.98IND, Vd(L) = 17.7; (3) adolescence age CL(L/h) = 1.49 × (WEIG/51.5)0.509 × 0.498VPA × 1.7IND, Vd(L) = 23.1; (4) whole age CL = 0.945 × [(WEIG/25)0.645] × (0.463VPA) × (1.94IND), V = 16.7 × (WEIG/25)0.919 (WEIG, total body weight; VPA, combination with valproate, yes = 1, no = 0; IND, combination with enzyme inducer, yes = 1, no = 0). The values of MPE, MAE and RMSE in age-stage-specific models were less than the ones in the whole-age model, which suggests the age-stage-specific models have better precision and accuracy than the whole-age model. CONCLUSION: PPK models of LTG in different age groups of epileptic children were successfully established. Weight and combination therapy were identified as significant covariates on LTG clearance. Compared with the whole-age model, the age-specific models are more reliable.

Structural basis of translation inhibition by a valine tRNA-derived fragment.

Translational regulation by non-coding RNAs is a mechanism commonly used by cells to fine-tune gene expression. A fragment derived from an archaeal valine tRNA (Val-tRF) has been previously identified to bind the small subunit of the ribosome and inhibit translation in Haloferax volcanii Here, we present three cryo-electron microscopy structures of Val-tRF bound to the small subunit of Sulfolobus acidocaldarius ribosomes at resolutions between 4.02 and 4.53 Å. Within these complexes, Val-tRF was observed to bind to conserved RNA-interacting sites, including the ribosomal decoding center. The binding of Val-tRF destabilizes helices h24, h44, and h45 and the anti-Shine-Dalgarno sequence of 16S rRNA. The binding position of this molecule partially overlaps with the translation initiation factor aIF1A and occludes the mRNA P-site codon. Moreover, we found that the binding of Val-tRF is associated with steric hindrance of the H69 base of 23S rRNA in the large ribosome subunit, thereby preventing 70S assembly. Our data exemplify how tRNA-derived fragments bind to ribosomes and provide new insights into the mechanisms underlying translation inhibition by Val-tRFs.

The Effect of Intense Pulsed Light Treatment for Chronic Hordeolum.

Objective: To evaluate the effect of intense pulsed light (IPL) in the treatment of chronic hordeolum. Methods: Patients with chronic hordeolum who underwent IPL treatment were enrolled in this study. According to the severity of hordeolum, the patients were treated with IPL 3 to 5 times. Patients' satisfaction and visual analog scale scores for ocular discomfort symptoms before and after treatment were collected. The number, congestion, long diameter, short diameter and area of nodules were also recorded and measured. Finally, eyelid margin signs, meibum quality, meibomian gland expressibility, meibomian gland dropout, tear meniscus height, and corneal fluorescein staining were scored. Results: 20 patients were enrolled in this study. The eyelid margins were congestive and swollen, with blunt rounding or irregularity. The meibum was cloudy or toothpaste-like. The meibomian gland expressibility, meibomian gland dropout and tear meniscus height were reduced. The cornea showed scattered fluorescein staining. After treatment, score of visual analog scale, congestion and size of nodules were significantly reduced. Eyelid margin signs, meibum quality, meibomian gland expressibility, tear meniscus height and corneal fluorescein staining scores were improved. Meibomian gland dropout had no significant change. No side effects occurred during treatment. Conclusions: IPL is beneficial for the treatment of chronic hordeolum.

Molecular signatures of soil-derived dissolved organic matter constrained by mineral weathering.

Dissolved organic matter (DOM) in soils drives biogeochemical cycling and soil functions in different directions depending on its molecular signature. Notably, there is a distinct paucity of information concerning how the molecular signatures of soil DOM vary with different degrees of weathering across wide geographic scales. Herein, we resolved the DOM molecular signatures from 22 diverse Chinese reference soils and linked them with soil organic matter and weathering-related mineralogical properties. The mixed-effects models revealed that the yields of DOM were determined by soil organic carbon content, whereas the molecular signature of DOM was primarily constrained by the weathering-related dimension. The soil weathering index showed a positive effect on the lability and a negative effect on the aromaticity of DOM. Specifically, DOM in highly weathered acidic soils featured more amino sugars, carbohydrates, and aliphatics, as well as less O-rich polyphenols and condensed aromatics, thereby conferring a higher DOM biolability and lower DOM aromaticity. This study highlights the dominance of the weathering-related dimension in constraining the molecular signatures and potential functions of DOM in soils across a wide geographic scale.

The structural plasticity of SCA7 domains defines their differential nucleosome-binding properties.

SAGA (Spt-Ada-Gcn5 acetyltransferase), a coactivator complex involved in chromatin remodelling, harbours both histone acetylation and deubiquitination activities. ATXN7/Sgf73 and ATXN7L3, two subunits of the SAGA deubiquitination module, contain an SCA7 domain characterized by an atypical zinc-finger. We show that the yeast Sgf73-SCA7 domain is not required to recruit Sgf73 into SAGA. Instead, it binds to nucleosomes, a property that is conserved in the human ATXN7-SCA7 domain but is lost in the ATXN7L3 domain. The solution structures of the SCA7 domain of both ATXN7 and ATXN7L3 reveal a new, common zinc-finger motif at the heart of two distinct folds, providing a molecular basis for the observed functional differences.

Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy.

AIM: To establish a population pharmacokinetics (PPK) model of levetiracetam in Chinese children with epilepsy. METHODS: A total of 418 samples from 361 epileptic children in Peking University First Hospital were analyzed. These patients were divided into two groups: the PPK model group (n=311) and the PPK validation group (n=50). Levetiracetam concentrations were determined by HPLC. The PPK model of levetiracetam was established using NONMEM, according to a one-compartment model with first-order absorption and elimination. To validate the model, the mean prediction error (MPE), mean squared prediction error (MSPE), root mean-squared prediction error (RMSPE), weight residues (WRES), and the 95% confidence intervals (95% CI) were calculated. RESULTS: A regression equation of the basic model of levetiracetam was obtained, with clearance (CL/F)=0.988 L/h, volume of distribution (V/F)=12.3 L, and K(a)=1.95 h(-1). The final model was as follows: K(a)=1.56 h(-1), V/F=12.1 (L), CL/F=1.04×(WEIG/25)(0.583) (L/h). For the basic model, the MPE, MSPE, RMSPE, WRES, and the 95%CI were 9.834 (-0.587-197.720), 50.919 (0.012-1286.429), 1.680 (0.021-34.184), and 0.0621 (-1.100-1.980). For the final model, the MPE, MSPE, RMSPE, WRES, and the 95% CI were 0.199 (-0.369-0.563), 0.002082 (0.00001-0.01054), 0.0293 (0.001-0.110), and 0.153 (-0.030-1.950). CONCLUSION: A one-compartment model with first-order absorption adequately described the levetiracetam concentrations. Body weight was identified as a significant covariate for levetiracetam clearance in this study. This model will be valuable to facilitate individualized dosage regimens.

A novel molybdenum disulfide nanosheet loaded Titanium/Zirconium bimetal oxide affinity probe for efficient enrichment of phosphopeptides in A549 cells.

In this paper, we developed a facile route for the preparation of a novel bimetal oxide affinity chromatography (MOAC) material. The TiO2/ZrO2@MoS2 was constructed by the electrostatic interaction between titanium oxide/zirconia (w:w, 10:1) and molybdenum disulfide nanosheet. The nanocomposite has the large specific surface area (186.30 m2⋅g-1) and pore volume (0.37 cm3⋅g-1). Compared with single-metal probes, the combination of bimetallic oxides probe (TiO2/ZrO2) and hydrophilicity MoS2 support offered multitudinous affinity sites for phosphopeptides capturing from tryptic digests of protein samples under 50% acetonitrile-1% trifluoroacetate conditions. Singnificant feasibility of the TiO2/ZrO2@MoS2 nanomaterial for the enrichment of phosphopeptides under optimal conditions was proved via the bovine serum albumin (BSA) and the mixtures of ß-casein. The phosphopeptide expression was identified using ultra-performance liquid chromatography (uHPLC) separation and-linear ion trap mass spectrometry (MSn). With these affinity characters of TiO2/ZrO2@MoS2, it exhibited higher binding capacity (25 mg⋅g-1), better selectivity for phosphopeptides from ß-casein/BSA (1:2000) tryptic digests, high sensitivity (1 fmol⋅µL-1) towards phosphopeptides from ß-casein tryptic digests, and great reusability of 8 cycles test for capturing phosphopeptides. In addition, the TiO2/ZrO2@MoS2 with high sensitivity and selectivity was successfully applied to enriching phosphopeptides from nonfat milk and human serum samples. More importantly, the TiO2/ZrO2@MoS2 was further successfully applied to multi-phosphopeptides enrichment, 1779 serine, threonine and tyrosine phosphosites can be identified in A549 cell protein tryptic digest. Compared with commercial TiO2 from enrichening 416 phosphopeptide from A549 cell lysates, the successful locating of 44 phosphosites were overlapped.