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Active fluids display collective phenomena such as active turbulence or odd viscosity, which refer to spontaneous complex and transverse flow. The simultaneous emergence of these seemingly separate phenomena is here reported in experiment for a chiral active fluid composed of a carpet of standing and spinning colloidal rods, and in simulations for synchronously rotating hard discs in a hydrodynamic explicit solvent. Experiments and simulations reveal that multi-scale eddies emerge, a hallmark of active turbulence, with a power-law decay of the kinetic-energy spectrum, a feature of self-similar dynamics. Moreover, the particles are dragged to the centre of the vortices, a telltale sign of odd viscosity. The weak compressibility of the system enables an explicit measurement of the odd viscosity in bulk via the relation between local vorticity and excess density. Our findings are relevant for the understanding of biological systems and for the design of microrobots with collective self-organized behavior. The investigation of a chiral active fluid composed of a carpet of standing and spinning colloidal rods, combined with simulations for synchronously rotating hard discs in a hydrodynamic explicit solvent reveals here the simultaneous occurrence and relation of two seemingly separate phenomena: active turbulence and odd viscosity. [ABSTRACT FROM AUTHOR]

Although straw returning combined with blended controlled-release urea fertilizer (BUFS) has been shown to improve wheat-maize rotation system productivity, their effects on greenhouse gas (GHG) emissions, carbon footprints (CF), and net ecosystem economic benefits (NEEB) are still unknown. Life cycle assessment was used to investigate a long-term (2013–2022) wheat-maize rotation experiment that included straw combined with two N fertilizer types [BUFS and (conventional urea fertilizer) CUFS] and straw-free treatments (BUF and CUF). The results showed that BUFS and CUFS treatments increased the annual yield by 13.8% and 11.5%, respectively, compared to BUF and CUF treatments. The BUFS treatment increased the yearly yield by 13.8% compared to the CUFS treatment. Since BUFS and CUFS treatments increased soil organic carbon (SOC) sink sequestration by 25.0% and 27.0% compared to BUF and CUF treatments, they reduced annual GHG emissions by 7.1% and 4.7% and CF per unit of yield (CF Y) by 13.7% and 9.6%, respectively. BUFS treatment also increased SOC sink sequestration by 20.3%, reduced GHG emissions by 10.7% and CF Y by 23.0% compared to CUFS treatment. It is worth noting that the BUFS and CUFS treatments increased the annual ecological costs by 41.6%, 26.9%, and health costs by 70.1% and 46.7% compared to the BUF and CUF treatments, but also increased the net yield benefits by 9.8%, 6.8%, and the soil nutrient cycling values by 29.2%, 27.3%, and finally improved the NEEB by 10.1%, 7.3%, respectively. Similar results were obtained for the BUFS treatment compared to the CUFS treatment, ultimately improving the NEEB by 23.1%. Based on assessing yield, GHG emissions, CF, and NEEB indicators, the BUFS treatment is recommended as an ideal agricultural fertilization model to promote sustainable and clean production in the wheat-maize rotation system and to protect the agroecological environment. • Compared with CUFS treatment, BUFS increased wheat and maize yield. • By storing organic carbon, BUFS reduced greenhouse gas emissions. • BUFS decreased carbon footprints for the wheat-maize rotation system. • BUFS improved the soil nutrient cycling values and net ecosystem economic benefits. [ABSTRACT FROM AUTHOR]

Background: An electroencephalogram (EEG) is the most dominant method for detecting epileptic seizures. However, the existing techniques use single-channel EEGs from public databases and the sample size is small.Objective: This study proposes a strategy to distinguish multichannel EEGs for health control, particularly the interictal and ictal multichannel EEGs of epileptic patients.Method: We calculated five features (variance, Pearson correlation coefficient, Hoeffding's D measure, Shannon entropy, inter-quartile range), which are based on maximal overlap discrete wavelet transform. These features were then fed into linear discriminant analysis for classification purposes. Finally, the proposed method was tested on data on 34 healthy people, 21 interictal patients and 30 ictal patients taken from a hospital.Results: Our experimental results show that the accuracy between healthy and epileptic seizures was 96.88% and the area under the curve (AUC) is 1. The accuracy between interictal and epileptic seizures was 94.12% and the AUC was 0.97. We also obtained an accuracy and AUC equal to 1 for discrimination of interictal EEGs from normal. Finally, we obtained an AUC of 0.83 and an accuracy of 85.88% for discrimination in these three classes. Therefore, our study achieves sufficient performance.Conclusions: Our proposed method can serve as an auxiliary tool for clinicians who wish to make clinical decisions and reduces the burden of detecting epileptic seizures. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A bi-dispersed bubble model incorporating lateral forces and bubble-induced turbulence is developed for the JLR simulation. • Bubble wake acceleration and hindrance effect is corrected in drag force of large and small bubble phase, respectively. • The agreement between simulating and experimental results in the riser and downcomer regions is fine. • Recommendation for draft tube position and A r / A d is provided by CFD simulation. Abstract A bi-dispersed bubble model incorporating lateral forces and bubble-induced turbulence is employed to simulate hydrodynamics in an up flow jet-loop reactor (JLR) operated in gas–liquid co-injection mode. In the model the bubble swarm effect on the drag force was differently described for the large and small bubble phases, where the drag force for the large bubble decreases with the gas holdup in accordance with the wake acceleration effect, while for the small bubble the drag force increases with the gas holdup in consideration of the hindrance effect of the bubble swarm. The simulated radial profiles of gas holdup and axial liquid velocity agree with the cold experiments, which shows that the different description of drag forces for the large and small bubbles is reasonable for correctly simulating the effect of superficial gas velocity on liquid circulation velocity. Effects of draft tube position (H C) and cross-sectional area ratio of riser to downcomer (A r / A d) are evaluated by model simulation. The results show that with the increase of H C and A r / A d , both overall gas holdup and liquid circulation velocity reach a maximum at H C = 0.06 m and A r / A d = 0.44, respectively. Recommendatory geometric parameters for the JLR design is: 0 < H C < 0.09 m, 0.4 < A r / A d < 0.7. [ABSTRACT FROM AUTHOR]

Soil organic carbon (SOC) sequestration effectively reduces global CO 2 emissions while ensuring crop production and sustainable agricultural development. Evaluating the effects of straw returning combined with controlled-release nitrogen (N) fertilizer on soil organic carbon (SOC) sequestration is necessary. We conducted a long-term (2013–2018) insitu field trial with six treatments: straw combined with no N and two N fertilizer types [no N fertilizer (CKS), conventional N fertilizer (BBFS) and controlled-release N fertilizer (CRFS)] and their corresponding no N and two N fertilizer treatments (CK, BBF, and CRF), each in three replicates. Overall, straw returning combined with N fertilizer (BBFS and CRFS) improves carbon storage and crop yield by changing aggregate distribution, with the effect of CRFS being more substantial. We further found CRFS treatment significantly increased SOC storage in small macro-aggregates (0.25–2 mm) by 9.2% and 28.4%, respectively, compared to BBFS and CKS treatments, which is mainly due to CRFS treatment increasing the proportion of small macro-aggregates (0.25–2 mm) by 8.1% and 20.1%, respectively, in contrast with BBFS and CKS treatments. Compared to BBFS and CKS treatments, CRFS treatment increased the fluorescence intensity of hydrophobic compounds in humic acid (HA) by 45.0% and 107.6%, respectively. Similarly, in small macro-aggregates (0.2–2.5 mm), CRFS treatment significantly increased the fluorescence intensity of hydrophobic compounds in HA. Lastly, structural equation modeling showed that straw returning treatments promote aggregate formation and carbon sequestration by increasing the fluorescence intensity of hydrophobic compounds in HA, ultimately increasing crop yield. Therefore, CRFS treatment is theoretically an effective method to promote SOC storage and increase crop yield and is a viable practice for sustainable agriculture. [Display omitted] • CRFS treatment enhanced C storage in small macro-aggregates. • In the CRFS treatment, the proportion of small macro-aggregate increased. • Appling CRFS treatment increased the fluorescence intensity of hydrophobic compounds. • CRFS treatment could increase crop yields by increasing organic carbon storage. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A modified drift-flux model was developed to predict “S-shape” relation of the overall gas holdup and gas velocity in JLR. • Gas–liquid co-injection mode results in larger gas holdup and liquid circulation velocity in comparison with gas jet alone mode. • Gas–liquid co-injection promotes the flow development. • JLR shows the largest liquid circulation compared with the BC and ALR. Abstract Hydrodynamics in an up flow jet-loop reactor (JLR) is experimentally investigated. The overall gas holdup, radial and axial distributions of local gas holdup and liquid velocity are presented. A modified drift-flux model was developed for correlating the “S-shape” relationship of overall gas holdup and gas velocity. Experiments show that the gas–liquid co-injection mode results in larger gas holdup and liquid circulation velocity than those of the gas jet alone mode. Liquid velocity distribution is more prone to reach the fully developed regime than the gas holdup, and the gas–liquid co-injection promotes the flow development. Comparison of JLR with the conventional bubble column (BC) and airlift reactor (ALR) shows that the JLR has a largest liquid circulation velocity, which is mostly beneficial to liquid mixing and solid suspension. [ABSTRACT FROM AUTHOR]

Controlled-release nitrogen (CRN) fertilizers gradually release N in synchronization with root nutrient absorption, increasing wheat productivity and soil fertility. The role of the soil microbial community in wheat productivity and soil fertility, on the other hand, is unknown. Amplicon sequencing and a co-occurrence network were used in this study to investigate the role of microbial symbiosis in controlling wheat productivity and soil fertility in a 12-year (2008–2019) calcareous soil field experiment. Furthermore, the effects of various fertilization models were compared. The soil microbial community was divided into three closely coexisting symbiotic modules (Modules #1, 2, and 3). Module #1 and #2 were dominated by bacteria, while Module #3e was dominated by fungi. Modules #1 and #3 had higher network transmissibility (closeness centrality) and stability (degree) than Module #2, and they had a significant positive correlation with wheat productivity and soil fertility. Then, using random forests analysis, we examined the relationship between the module microorganism and wheat productivity and soil fertility. Module #1 microorganisms contributed more to wheat productivity and soil fertility than Module #3 microorganisms, and the microorganisms with significant relationships had a more complex composition (P < 0.05), primarily composed of Actinobacteria, Chloroflexi, Gemmatimonadetes, and Proteobacteria. Module #3, on the other hand, was primarily composed of Ascomycota. Finally, according to the structural equation model, CRN fertilizers could significantly improve wheat productivity and soil fertility when compared to soluble N (SN) fertilizers by increasing the diversity of the symbiotic module. In conclusion, our study discovered that Modules #1 and 3 are closely related to wheat productivity and soil fertility. The composition of module microorganisms, as well as the role of CRN fertilizer in symbiotic modules, were also investigated. [Display omitted] • Controlled-release nitrogen (CRN) fertilizer improved wheat productivity and soil fertility. • Long-term CRN fertilization altered soil microbial community structure. • Key symbiotic module significantly affected wheat productivity and soil fertility. • CRN increased the diversity of the key symbiotic module. [ABSTRACT FROM AUTHOR]

Spt5 (NusG in bacteria) is the only RNA polymerase-associated factor known to be conserved in all three domains of life. In archaea and eukaryotes, Spt5 associates with Spt4, an elongation factor that is absent in bacteria, to form a functional heterodimeric complex. Previous studies suggest that the Spt4:Spt5 complex interacts directly with DNA at the double-stranded DNA exit tunnel of RNA polymerase to regulate gene transcription. In this study, the DNA-binding ability of Spt4:Spt5 from the archaeon Methanocaldococcus jannaschii was confirmed via nuclear magnetic resonance chemical shift perturbation and fluorescence polarization assays. Crystallographic analysis of the full-length Mj Spt4:Spt5 revealed two distinct conformations of the C-terminal KOW domain of Spt5. A similar alkaline region was found on the Spt4:Spt5 surface in both crystal forms, and identified as double-stranded DNA binding patch through mutagenesis-fluorescence polarization assays. Based on these structural and biochemical data, the Spt4:Spt5-DNA binding model was built for the first time. [ABSTRACT FROM AUTHOR]

A novel phase inversion model was developed to describe the hydrodynamics in turbulent fluidized beds. The proposed model was coupled by a bubble–emulsion two phase model and a gas–cluster two phase model, which was derived from the typical mesoscale structures of two coexisting regions in turbulent fluidized beds. In the dense, bubbling region, the bubble-based interphase forces were used, while in the dilute, dispersed region, the cluster-based interphase forces were developed. The criterion of phase inversion, namely bubble-to-gas, emulsion-to-cluster, or vice versa, was also proposed and tested. Simulation results were compared with experimental data under different conditions to validate the model. The interphase forces acting on bubble or cluster were analyzed to study the radial nonuniformity of solid volume fraction. A coarse grid was utilized in this model, showing more capacity for the industrial scale-ups. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the risk stratification among elderly Nasopharyngeal carcinoma (NPC) patients (≥60 years old) and select the beneficiaries from concurrent chemotherapy (CCRT) combined with induction chemotherapy (IC). Materials and Methods: A total of 909 elderly non‐metastatic NPC patients treated with cisplatin‐based CCRT or IC + CCRT between January 2007 and December 2016 were included. Prognostic nomograms were generated according to clinical characteristics and serum biomarkers. The survival outcomes of patients treated with CCRT versus IC + CCRT were compared in three well‐matched risk groups (high, medium, and low risk) after PSM analysis. Benefit of IC in people older or younger than 70 years and effect of different IC regimens and cycles on prognosis were analyzed. Results: Nomograms of overall survival (OS) (C‐index: 0.64, 95% CI, 0.61–0.89) and disease special survival (DSS) (C‐index: 0.65, 95% CI, 0.62–0.71) showed good prognostic accuracy. The nomogram for DSS included variables of age, gender, ACE, EBV DNA, N stage, and T stage. OS included variables of age, smoking history, ACE, ALB, EBV DNA, N stage, and T stage. The corresponding 5‐year OS rates of high, medium and low risk groups were 87.4%, 82.2%, and 60.9%, respectively (p < 0.001), while the 5‐year DSS rates were 92.2%, 84.3%, and 69.0%, respectively (p < 0.001). In the high risk group, IC + CCRT led to significantly higher 5‐year OS and DSS rate compared with CCRT (5‐year OS rate, 73.5% versus 51.8%, p = 0.006; 5‐year DSS rate, 81.4% versus 61.3%, p = 0.002). While in the medium and low risk groups, OS and DSS were not significantly different (OS: p = 0.259, 0.186; DSS: p = 0.29, 0.094). Subgroup analysis showed in the high risk group, only people younger than 70 years old could benefit from IC. TPF and IC cycles of three could lead to the best survival results. Conclusion: Compared with CCRT, OS, and DSS among high risk elderly patients were significantly improved by the addition of IC in patients younger than 70 years old. TPF and three IC cycles were recommended. [ABSTRACT FROM AUTHOR]

The Nit (nitrilase-like) protein subfamily constitutes branch 10 of the nitrilase superfamily. Nit proteins are widely distributed in nature. Mammals possess two members of the Nit subfamily, namely Nit1 and Nit2. Based on sequence similarity, yeast Nit2 (yNit2) is a homologue of mouse Nit1, a tumour-suppressor protein whose substrate specificity is not yet known. Previous studies have shown that mammalian Nit2 (also a putative tumour suppressor) is identical to ω-amidase, an enzyme that catalyzes the hydrolysis of α-ketoglutaramate (α-KGM) and α-ketosuccinamate (α-KSM) to α-ketoglutarate (α-KG) and oxaloacetate (OA), respectively. In the present study, crystal structures of wild-type (WT) yNit2 and of WT yNit2 in complex with α-KG and with OA were determined. In addition, the crystal structure of the C169S mutant of yNit2 (yNit2-C169S) in complex with an endogenous molecule of unknown structure was also solved. Analysis of the structures revealed that α-KG and OA are covalently bound to Cys169 by the formation of a thioester bond between the sulfhydryl group of the cysteine residue and the γ-carboxyl group of α-KG or the β-carboxyl group of OA, reflecting the presumed reaction intermediates. However, an enzymatic assay suggests that α-KGM is a relatively poor substrate of yNit2. Finally, a ligand was found in the active site of yNit2-C169S that may be a natural substrate of yNit2 or an endogenous regulator of enzyme activity. These crystallographic analyses provide information on the mode of substrate/ligand binding at the active site of yNit2 and insights into the catalytic mechanism. These findings suggest that yNit2 may have broad biological roles in yeast, especially in regard to nitrogen homeostasis, and provide a framework for the elucidation of the substrate specificity and biological role of mammalian Nit1. [ABSTRACT FROM AUTHOR]

Fungal laccases are oxidoreductases that belong to the multinuclear copper-containing oxidases. They are able to oxidize a wide range of substrates, preferably phenolic compounds, which makes them suitable for employment in the bioremediation of soil and water as well as in other biotechnological applications. Here, the structural analysis of natural laccase B (LacB) from Trametes sp. AH28-2 is presented. This structure provides the opportunity to study the natural post-translational modifications of the enzyme. The overall fold shows a high homology to those of previously analyzed laccases with known three-dimensional structure. However, LacB contains a new structural element, a protruding loop near the substrate-binding site, compared with the previously reported laccase structures. This unique structural feature may be involved in modulation of the substrate recognition of LacB. [ABSTRACT FROM AUTHOR]

Abstract: AaHIV, a P-III-type snake venom metalloproteinase (SVMP), consists of metalloproteinase/disintegrin/cysteine-rich (MDC) domains and is homologous to a disintegrin and metalloproteinase (ADAM) family proteins. Similar to brevilysin H6 and jararhagin, AaHIV can easily autolyse to release a stable protein named acucetin, which contains disintegrin-like and cysteine-rich domains. In this study, we determined the crystal structure of AaHIV and investigated the autolysis mechanism. Based on the structure of AaHIV and the results from docking experiments, we present a new model for target recognition in which two protein molecules form a functional unit, and the DC domain of one molecule is used for target recognition while the M-domain of the other is used for target proteolysis. Our results shed new light on the mechanism of target recognition and processing in ADAM/reprolysin family proteins. [Copyright &y& Elsevier]

• Blended controlled-release nitrogen fertilizer with straw returning (CRFS) increased the abundance of soil microorganisms. • CRFS promoted root growth and nitrogen uptake of wheat. • CRFS improved wheat yield, nitrogen use efficiency, and economic return. Microbial activities and nitrogen (N) availability in soil directly affect root morphology and consequently crop yield. These relationships are even more critical at the filling stage of wheat due to the grain formation. The objective of this study was to compare effects of blended controlled-release N fertilizer (CRFS) and conventional urea (BBFS) on soil microflora, soil N content, and root growth of wheat at the filling stage in a field with straw return for seven years. The method of 16 s rRNA and ITS high-throughput sequencing was used to probe soil microbial status, and the in-situ root scanner was used for in-situ observation and monitoring of wheat root morphology during two growing seasons. The results showed that CRFS increased the relative abundance of Penicillium and Aspergillus fungal genera and reduced the operational taxonomic unit of nitrifying bacteria of the genus Nitrospira compared to BBFS treatment. Nitrate, ammonium, total N, and organic matter in soils treated CRFS were 15.8 %, 10 %, 7.5 %, and 11.6 % higher than these in soils treated with BBFS, respectively, while the total root length, root surface area, and root volume from CRFS treatment were 57.6%, 48.8 %, and 54.1 % higher than these from BBFS, respectively. Above-ground growth of wheat showed that CRFS increased plant height by 5.8–12.6 %, net photosynthetic rate by 13.5–22.2 %, N content of stems and spikes by 10.0 % and 64.1 %, respectively compared to BBFS. Wheat yield and economic efficiency were increased by 9.9–46.8 %, 11.6–41.7 %, respectively with CRFS treatments than these with BBFS treatments. Wheat received reduced application rate (2/3) of CRFS had similar availability of N and plant growth as the full rate of BBFS. Therefore, using blended controlled-release N fertilizer is a practically and environmentally feasible approach for wheat production in the straw retuning wheat-corn rotation system. [ABSTRACT FROM AUTHOR]

With the changing times, obesity has become a characteristic epidemic in the context of the current era. Insulin resistance (IR) is most commonly caused by obesity, and IR is a common basis of the pathogenesis of many diseases such as cardiovascular disease, nonalcoholic fatty liver disease, and type 2 diabetes, which seriously threaten human life, as well as health. A major pathogenetic mechanism of obesity-associated IR has been found to be chronic low-grade inflammation in adipose tissue. Specialized pro-resolving mediators (SPMs) are novel lipid mediators that both function as "stop signals" for inflammatory reaction and promote inflammation to subside. In this article, we summarize the pathogenesis of obesity-associated IR and its treatments and outline the classification and biosynthesis of SPMs and their mechanisms and roles in the treatment of obesity-associated IR in order to explore the potential of SPMs for treating metabolic diseases linked with obesity-associated IR. [ABSTRACT FROM AUTHOR]

In this paper, we establish an in situ visualization analysis method to image the spatial distribution of metabolites in different parts (sclerotium, coremium) and different microregions of Cordyceps cicadae (C. cicadae) to achieve the in situ visual characterization of tissues for a variety of metabolites such as nucleosides, amino acids, polysaccharides, organic acids, fatty acids, and so on. The study included LC–MS chemical composition identification, preparation of C. cicadae tissue sections, DEDI-MSI analysis, DESI combined with Q-TOF/MS to obtain high-resolution imaging of mass-to-charge ratio and space, imaging of C. cicadae in positive–negative ion mode with a spatial resolution of 100 μm, and localizing and identifying its chemical compositions based on its precise mass. A total of 62 compounds were identified; nucleosides were mainly distributed in the coremium, L-threonine and DL-isoleucine, and other essential amino acids; peptides were mainly distributed in the sclerotium of C. cicadae; and the rest of the amino acids did not have a clear pattern; sugars and sugar alcohols were mainly distributed in the coremium of C. cicadae; organic acids and fatty acids were distributed in the nucleus of C. cicadae more than in the sclerotium, and the mass spectrometry imaging method is established in the research. The mass spectrometry imaging method established in this study is simple and fast and can visualize and analyse the spatial distribution of metabolites of C. cicadae, which is of great significance in characterizing the metabolic network of C. cicadae, and provides support for the quality evaluation of C. cicadae and the study of the temporal and spatial metabolic network of chemical compounds. [ABSTRACT FROM AUTHOR]

Objectives: The mechanisms underlying the therapeutic effects of Si-Zhi Wan (SZW), a traditional Chinese medicine used to treat osteoporosis (OP), remain unknown. This study investigated the therapeutic effects of SZW on mice that underwent ovariectomy (OVX) and underlying mechanisms thereof. Methods: We established an in vivo model of OP by performing OVX in mice. Microcomputed tomography (Micro-CT) was used to assess changes in bone characteristics of mice following SZW administration for 4 weeks. H&E staining revealed alterations in bone tissues of mice. Osteoclastogenesis in mouse bone tissue was observed using tartrate-resistant acid phosphatase staining and western blotting. Furthermore, we examined the impact of SZW on osteoclastogenesis in vitro using receptor activator of nuclear factor kappa-B ligand (RANKL). Finally, we explored the regulatory effects of SZW on osteoclast autophagy and the AMPK pathway. Key findings: The results demonstrated that high-dose SZW reversed changes in bone density parameters caused by OVX, including bone volume (BV), BV/total volume, trabecular number, and trabecular spacing (P = 0.0007, 0.0035, 0.0114, and 0.0182, respectively), and stimulated the formation of bone trabeculae in mice (P < 0.0001). Furthermore, SZW suppressed osteoclast formation in mice with OVX and inhibited osteoclast formation induced by RANKL. Mechanistically, SZW inhibited osteoclast precursor cell autophagy through the AMPK pathway. Conclusions: SZW effectively inhibited the autophagy of osteoclast precursors by regulating the AMPK pathway, thereby exerting anti-osteoclastogenic effects and serving as an alternative therapy for OP. [ABSTRACT FROM AUTHOR]

Controlled-release urea (CRUs), including polymer-coated urea (PCU), sulfur-coated urea (SCU), and polymer/sulfur dual layer-coated urea (PSCU), have been demonstrated to increase crop yield and nitrogen use efficiency (NUE). However, the effects of long-term application of CRUs on soil microbial community and function remain unclear. In this study, a 12-year (2009–2021) 24-season wheat -maize rotation lysimeter experiment was studied to investigate the effects of PCU, SCU, and PSCU on soil microbial community composition and function. Wheat was grown, soil chemical properties were analyzed, and soil biological properties including enzyme activities and microbial community structure and function at the wheat filling stage were determined in 2021. The results showed that soil organic matter (SOM) contents were markedly increased by 3.1∼5.0% under the CRUs compared to conventional urea. Meanwhile, some carbon, nitrogen, and sulfur cycle enzyme activities, including cellulase (CE), urease and arylsulfatase (AS), were significantly enhanced by 23.4∼32.4%, 6.6∼32.1%, and 2.5∼3.7% under the CRUs compared to conventional urea, respectively. Redundancy analysis indicated that changes in bacterial and fungal communities were driven by SOM. Co-occurrence network analysis showed that wheat growth promotion by the CRUs was strongly linked to the high relative abundance (Z-score) of bacterial and fungal module 1, which included such plant growth-promoting microorganisms (PGPMs) as Arthrobacter , Bryobacter , Bradyrhizobium , Microscypha , and Marasmius. Compared with PCU, SCU and PSCU showed a better effect in increasing the relative abundances of PGPMs while inhibiting the growth of nitrobacteria, denitrifying bacteria, and plant pathogens, thereby better promoting wheat yields and reducing N loss and plant disease. Of the three CRUs, SCU and PSCU have significantly increased SOM, which provided sufficient substrate for the growth of PGPMs, thus increasing wheat yield. This study provides a support for long-term CRUs application and sustainable agriculture. [Display omitted] • Long-term CRUs application increased soil enzyme activities, soil fertility, and wheat yield. • Long-term CRUs application altered soil microbial diversity and community structure. • Long-term CRUs application increased plant growth-promoting microorganisms and decreased plant pathogens. • Wheat yield was associated with the relative abundances of key microbial modules. [ABSTRACT FROM AUTHOR]

Quercetin, a typical flavonoid derived from a common natural plant, has multiple biological activities. Previous research in animal models has demonstrated the effectiveness of quercetin in treating rheumatoid arthritis (RA). The pharmacological effects and probable mechanisms of quercetin were evaluated in this study. Three databases, PubMed, Web of Science, and Embase, were searched for relevant studies from the creation of the databases to November 2022. Methodological quality was assessed using the SYRCLE risk of bias tool. STATA 15.1 was used to perform the statistical analysis. This research included 17 studies involving 251 animals. The results indicated that quercetin was able to reduce arthritis scores, paw swelling, histopathological scores, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), malondialdehyde (MDA), reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), nuclear factor kappa B (NF-kB) and increase interleukin-10 (IL-10), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase-1 (HO-1). These may be related to quercetin's potential anti-inflammatory, anti-oxidative stress, and osteoprotective properties. However, more high-quality animal studies are needed to assess the effect of quercetin on RA. Additionally, the safety of quercetin requires further confirmation. Given the importance of the active ingredient, dose selection and the improvement of quercetin's bioavailability remain to be explored. [ABSTRACT FROM AUTHOR]

Abstract By bearing a papain-like core structure and a cysteine-based catalytic triad, deamidase can convert glutamine to glutamic acid or asparagine to aspartic acid to modify the functions of host target proteins resulting in the blocking of eukaryotic host cell function. Legionella pneumophila effector Lpg2148 (MvcA) is a deamidase, a structural homolog of cycle inhibiting factor (Cif) effectors. Lpg2148 and Cif effectors are functionally diverse, with Lpg2148 only catalyzing ubiquitin but not NEDD8. However, a detailed understanding of substrate specificity is still missing. Here, we resolved the crystal structure of Lpg2148 at 2.5 Å resolution and obtained rigid-body modeling of Lpg2148 with C-terminus deleted ubiquitin (1–68) (ubΔc) complex using HADDOCK, which shows that the C-terminus of ubiquitin is flexible in recognition. We also conducted the truncated analysis to demonstrate that Leu71 of ubiquitin is necessary for its interaction with Lpg2148. Moreover, Val33 of Lpg2148 at the edge of a channel plays a vital role in the interaction and is limited by the length of the C-terminus of ubiquitin, which may help to explain the selectivity of ubiquitin over NEDD8. In summary, these results enrich our knowledge of substrate recognition of deamidase. Graphical abstract Image 1 Highlights • Docking of Lpg2148/ub∆c model provides a clue that the C-terminus of ubiquitin plays a vital role in interaction. • The Leu71 in C-terminus of ubiquitin is necessary for interaction and His68 is important in deamidation. • The Val33 of Lpg2148 plays a vital role in the interaction and is limited by the length of the C-terminus of ubiquitin. [ABSTRACT FROM AUTHOR]

Synaptotagmins constitute a family of multifunctional integral membrane proteins found predominantly on vesicles in neural and endocrine tissues. 17 isoforms of synaptotagmin family in mammals have been identified, 7 isoforms among them are known to be able to bind Ca 2+ via their C2 domains. This study presents the crystal structure of the first C2 domain (C2A domain) of synaptotagmin 5 complexed with Ca 2+ at 1.90 Å resolution. Comparison of the Ca 2+ -binding pocket of synaptotagmin 5 C2A domain with other synaptotagmin C2 domains demonstrated that a serine residue locating at Ca 2+ -binding loop probably responsible to the conformational variation of Ca 2+ -binding pocket, and thus impacts the Ca 2+ -binding mechanism of C2 domain, which is verified by structural analysis of the serine mutant and Ca 2+ -binding assays via isothermal titration calorimetry. Alteration of Ca 2+ -binding mechanism might be correlated with different Ca 2+ response rates of synaptotagmins, which is the basis of the functions of synaptotagmins in regulating various types of Ca 2+ -triggered vesicle-membrane fusion processes. [ABSTRACT FROM AUTHOR]

It has been reported that tumor growth and proliferation correspond to mitochondrial dysfunction and that the tumor cellular microenvironment plays a key role in tumor progression, representing an area that might be manipulated to confer therapeutic anti-tumor benefits. In this article, we have identified mitochondrial genes, largely nuclear-encoded genes, which are differentially expressed in breast cancer epithelial and stromal cells compared to cells from normal breast tissues. We determined that gene expression of the mitochondrial membrane respiratory chain complex I and IV and ATP synthesis were reduced in both in epithelial and stromal cancer cells compared to normal breast cells. We also found transport-related genes were significantly more highly expressed in breast cancer epithelial cells. Our data also suggest that mitochondria are likely to proliferate in breast cancer stromal cells, which is supported by the observation that MRPL12, POLG, and RNASEH1 are all up-regulated in cancerous stromal cells. In addition, we present an improved simulated annealing algorithm, SANetWalker, which can be used to detect the functional module. At the same time, this method has a minimal effect on network topology and can be used to identify the highest confidence functional module. Using SANetWalker, we obtained the highest confidence (90%) functional module with a fumarate hydratase (FH)-centered network with 40 nodes and 107 edges. Functional analysis revealed that glutamine metabolism genes were significantly up-regulated in both epithelial and stromal cells from breast cancer tissues, which implicates glutamine metabolism in breast cancer growth and metastasis. [ABSTRACT FROM AUTHOR]

Summary Histone chaperones are critical for guiding specific post-transcriptional modifications of histones, safeguarding the histone deposition (or disassociation) of nucleosome (dis)assembly, and regulating chromatin structures to change gene activities. HAT1-interacting factor 1 (Hif1) has been reported to be an H3-H4 chaperone and to be involved in telomeric silencing and nucleosome (dis)assembly. However, the structural basis for the interaction of Hif1 with histones remains unknown. Here, we report the complex structure of Hif1 binding to H2A-H2B for uncovering the chaperone specificities of Hif1 on binding to both the H2A-H2B dimer and the H3-H4 tetramer. Our findings reveal that Hif1 interacts with the H2A-H2B dimer and the H3-H4 tetramer via distinct mechanisms, suggesting that Hif1 is a pivotal scaffold on alternate binding of H2A-H2B and H3-H4. These specificities are conserved features of the Sim3-Hif1-NASP interrupted tetratricopeptide repeat proteins, which provide clues for investigating their potential roles in nucleosome (dis)assembly. [ABSTRACT FROM AUTHOR]

Smart grids are being expanded in scale with the increasing complexity of the equipment. Edge computing is gradually replacing conventional cloud computing due to its low latency, low power consumption, and high reliability. The CORDIC algorithm has the characteristics of high-speed real-time processing and is very suitable for hardware accelerators in edge computing devices. The iterative calculation method of the CORDIC algorithm yet leads to problems such as complex structure and high consumption of hardware resource. In this paper, we propose an RDP-CORDIC algorithm which pre-computes all micro-rotation directions and transforms the conventional single-stage iterative structure into a three-stage and multi-stage combined iterative structure, thereby enabling it to solve the problems of the conventional CORDIC algorithm with many iterations and high consumption. An accuracy compensation algorithm for the direction prediction constant is also proposed to solve the problem of high ROM consumption in the high precision implementation of the RDP-CORDIC algorithm. The experimental results showed that the RDP-CORDIC algorithm had faster computation speed and lower resource consumption with higher guaranteed accuracy than other CORDIC algorithms. Therefore, the RDP-CORDIC algorithm proposed in this paper may effectively increase computation performance while reducing the power and resource consumption of edge computing devices in smart grid systems. [ABSTRACT FROM AUTHOR]

l -amino acid oxidases/deaminases (LAAOs/LAADs) are a class of oxidoreductases catalyzing the oxidative deamination of l -amino acids to α-keto acids. They are widely distributed in eukaryotic and prokaryotic organisms, and exhibit diverse substrate specificity, post-translational modifications and cellular localization. While LAAOs isolated from snake venom have been extensively characterized, the structures and functions of LAAOs from other species are largely unknown. Here, we reported crystal structure of a bacterial membrane-bound LAAD from Proteus vulgaris ( pv LAAD) in complex with flavin adenine dinucleotide (FAD). We found that the overall fold of pv LAAD does not resemble typical LAAOs. Instead it, is similar to d -amino acid oxidases (DAAOs) with an additional hydrophobic insertion module on protein surface. Structural analysis and liposome-binding assays suggested that the hydrophobic module serves as an extra membrane-binding site for LAADs. Bacteria from genera Proteus and Providencia were found to encode two classes of membrane-bound LAADs. Based on our structure, the key roles of residues Q278 and L317 in substrate selectivity were proposed and biochemically analyzed. While LAADs on the membrane were proposed to transfer electrons to respiratory chain for FAD re-oxidization, we observed that the purified pv LAAD could generate a significant amount of hydrogen peroxide in vitro , suggesting it could use dioxygen to directly re-oxidize FADH 2 as what typical LAAOs usually do. These findings provide a novel insights for a better understanding this class of enzymes and will help developing biocatalysts for industrial applications. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis is a common precursor of ventricular dysfunction and heart failure. We investigated the role of oxidative stress in myocardial fibrosis and the protective effect of panaxatriol saponin (PTS) against myocardial infarction (MI)-induced cardiac fibrosis and explored the underlying mechanisms. In vitro , cell viability was tested using a cell counting kit. The reactive oxygen species (ROS) levels including hydrogen peroxide (H 2 O 2) and superoxide anion (O 2 •−) were determined. Antioxidant enzyme levels were determined by immunofluorescence and Western blotting. Enzyme-linked immunosorbent assays, echocardiography, histological analysis, immunofluorescence staining, and molecular analysis were performed. Nuclear factor erythroid 2–related factor 2 (Nrf2) activation was evaluated by molecular docking and immunoprecipitation. Finally, the mechanism by which PTS inhibits cardiac fibrosis was investigated using the Nrf2 activator ML334 and a small interfering RNA for Nrf2. Ang II-induced differentiation of cardiac fibroblasts was associated with oxidative stress, characterized by upregulation of α-smooth muscle actin, increased reactive oxygen species production, and inhibition of superoxide dismutase-1 and heme oxygenase expression. In addition, PTS improved cardiac function and ameliorated cardiac fibrosis in MI rats. It also reduced Ang II-induced fibroblast differentiation and proliferation, suppressed oxidative stress, and disrupted the Kelch-like ECH-associated protein 1 (Keap1)–Nrf2 interaction by directly blocking the Nrf2 binding site in Keap1. Overexpression of Nrf2 by ML334 enhanced the antifibrotic effect of PTS. However, genetic ablation of Nrf2 abrogated the antifibrotic effect of PTS in cardiac fibrosis. Taken together, our findings suggest that Nrf2 has promise as a target and PTS as a therapeutic agent for cardiac fibrosis. [Display omitted] • Ang II-induced differentiation of cardiac fibroblasts is associated with enhanced oxidative stress. • PTS is an antioxidant that attenuates Ang II-induced oxidative stress in cardiac fibroblasts. • PTS disrupts the interaction between Nrf2 with Keap1 by binging with the Kelch domain of Keap1. • The antifibrotic effect of PTS depends on its antioxidant activity. [ABSTRACT FROM AUTHOR]

Treatment options for hepatic fibrosis, a prevalent liver condition closely linked to cirrhosis, are currently limited. While Guizhi Fuling Wan (GFW), a pill derived from traditional Chinese herbs, has been reported to possess hepatoprotective properties, its therapeutic effect and mechanism in hepatic fibrosis remain elusive. This study aimed to evaluate the anti-fibrotic impact of GFW and its underlying mechanisms in both in vivo and in vitro settings. Tetrachloromethane (CCl 4) was used to induce hepatic fibrosis in male rats. In vitro , activation of hepatic stellate cells (HSCs) was triggered by platelet-derived growth factor-BB (PDGF-BB). In vivo , liver function, pathological alterations, and HSC activation were evaluated. Additionally, the impact of GFW on the activated phenotypes of Lieming Xu-2 (LX-2) cells was examined in vitro. Network pharmacology was employed to identify the potential targets of GFW in hepatic fibrosis. Lastly, the impact of GFW on the PTEN/AKT/mTOR pathway and PTEN ubiquitination in HSCs was investigated. GFW alleviated CCl 4 -induced liver damage and scarring in rats in a dose-dependent manner and suppressed HSC activation in vivo. Moreover, GFW inhibited the proliferation, migration, differentiation, and extracellular matrix (ECM) production of activated HSCs in vitro. GFW also promoted autophagy and apoptosis of HSCs. Meanwhile, network pharmacology and in vitro studies suggested that GFW inhibits the AKT/mTOR pathway by preventing PTEN degradation by suppressing ubiquitination. GFW attenuates Ccl 4 -induced hepatic fibrosis in male rats by regulating the PTEN/AKT/mTOR signaling pathway, positioning it as a potential candidate for the treatment of hepatic fibrosis. [Display omitted] • GFW ameliorates the liver damage and fibrosis caused by tetrachloromethane in rats, suggesting potential as a supplementary or alternative therapy for hepatic fibrosis. • GFW inhibits the activation of hepatic stellate cells, and promotes their autophagy and apoptosis, thereby attenuating hepatic fibrosis. • GFW intervents PTEN ubiquitination degradation to consequent inhibition of the Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

The yeast Paf1 complex (Paf1C), which is composed of the proteins Paf1, Cdc73, Ctr9, Leo1 and Rtf1, accompanies RNA polymerase II from the promoter to the 3′-end formation site of mRNA- and snoRNA-encoding genes. As one of the first identified subunits of Paf1C, yeast Cdc73 (yCdc73) takes part in many transcription-related processes, including binding to RNA polymerase II, recruitment and activation of histone-modification factors and communication with other transcriptional activators. The human homologue of yCdc73, parafibromin, has been identified as a tumour suppressor linked to breast, renal and gastric cancers. However, the functional mechanism of yCdc73 has until recently been unclear. Here, a 2.2 Å resolution crystal structure of the highly conserved C-terminal region of yCdc73 is reported. It revealed that yCdc73 appears to have a GTPase-like fold. However, no GTPase activity was observed. The crystal structure of yCdc73 will shed new light on the modes of function of Cdc73 and Paf1C. [ABSTRACT FROM AUTHOR]

In bacteria and eukaryotes, the last two steps of de novo purine biosynthesis are catalyzed by bifunctional purine-biosynthesis protein (PurH), which is composed of two functionally independent domains linked by a flexible region. The N-terminal domain possesses IMP cyclohydrolase activity and the C-terminal domain possesses aminoimidazole-4-carboxamide ribonucleotide transformylase activity. This study reports the expression, purification, crystallization and preliminary X-ray crystallographic analysis of PurH from Escherichia coli with an N-terminal His6 tag. The crystals diffracted to a maximum resolution of 3.05 Å and belonged to the monoclinic space group P21, with unit-cell parameters a = 76.37, b = 132.15, c = 82.64 Å, β = 111.86°. [ABSTRACT FROM AUTHOR]

Snake-venom thrombin-like enzymes (SVTLEs) are serine proteases that are widely distributed in snakes from the Crotalinae subfamily of the Viperidae. In contrast to other snake-venom serine proteases, they have a biochemical activity similar to that of thrombin and play an important role in the process of blood coagulation. However, SVTLEs cannot activate factor VIII, which is essential in blood-clot stabilization. Consequently, blood clots produced by SVTLEs are not stable and are cleared rapidly. This characteristic makes SVTLEs attractive as potential candidates for antithrombotic therapy. Saxthrombin, an SVTLE from Gloydius saxatilis, was purified and crystallized to obtain a high-quality crystal, from which data were acquired to 1.43 Å resolution. Preliminary X-ray diffraction analysis showed that the crystal belonged to space group C2, with unit-cell parameters a = 94.2, b = 52.2, c = 50.1 Å, β = 96.7°. The crystal structure was determined by molecular replacement and the final R factor was 18.69%; the Rfree was 20.01%. This is the first report of a crystal structure of an SVTLE. Saxthrombin belongs to the typical α/β-hydrolase fold of serine proteases. Its structure was compared with those of thrombin and other snake-venom serine proteases. The observed differences in the amino-acid composition of the loops surrounding the active site appear to contribute to different surface-charge distributions and thus alter the shape of the active-site cleft, which may explain the differences in substrate affinity. [ABSTRACT FROM AUTHOR]

The interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. We demonstrated that anfibatide interferds with both VWF and thrombin binding, inhibited ristocetin/botrocetin- and low-dose thrombin-induced human platelet aggregation, and decreased thrombus volume and stability in blood flowing over collagen. In a single-center, randomized, and open-label phase I clinical trial, anfibatide was administered intravenously to 94 healthy volunteers either as a single dose bolus, or a bolus followed by a constant rate infusion of anfibatide for 24 h. Anfibatide inhibited VWF-mediated platelet aggregation without significantly altering bleeding time or coagulation. The inhibitory effects disappeared within 8 h after drug withdrawal. No thrombocytopenia or anti-anfibatide antibodies were detected, and no serious adverse events or allergic reactions were observed during the studies. Therefore, anfibatide was well-tolerated among healthy subjects. Interestingly, anfibatide exhibited pharmacologic effects in vivo at concentrations thousand-fold lower than in vitro, a phenomenon which deserves further investigation. Trial registration: Clinicaltrials.gov NCT01588132. [ABSTRACT FROM AUTHOR]

We simulate the self-assembly of active colloidal molecules from binary mixtures of spherical particles using a Brownian dynamics algorithm. These particles interact via phoretic interactions, which are determined by two independently tunable parameters, surface activity and surface mobility. In systems composed of equal-size particles, we observe the formation of colloidal molecules with well-defined coordination numbers and spatial arrangement, which also display distinct dynamic functions, such as resting, translating, and rotating. By changing the size ratio to 2 : 1 between the two species, we further observe the formation of colloidal molecules with new structures arising from breaking the size symmetry. By tuning the mutual interactions between the smaller species via their surface mobility, we are able to control their spacing as well as the coordination number of the colloidal molecules. This study highlights the importance of tuning surface parameters and size asymmetry in controlling the structure and the active dynamics of colloidal molecules. [ABSTRACT FROM AUTHOR]

[Display omitted] • Surface spectroscopy reveals the role of hydroxyl groups in the oxidation of aldehyde groups in aqueous phase. • The isotope distinguishes the role of active oxygen species in furfural oxidation. • Experiments were designed to verify the cyclic law of hydroxyl and active oxygen species. • The mechanism of furfural oxidation to furoic acid under base-free conditions was proposed and verified. δ-MnO 2 shows potential application in furfural base-free oxidation to furoic acid. While, its catalytic mechanism was unclear, which limited the further improvement of the catalytic activity. Therefore, three δ crystal MnO 2 with different hydroxyl and active oxygen species concentrations were prepared and applied in the furfural oxidation reaction. IR, Furfural-IR, O 2 -TPD, H 2 O-18O 2 -TPD, and XPS techniques characterized the hydroxyl and active oxygen species. The results show that the hydroxyl group on δ-MnO 2 is important in absorbing and attacking furfural to form geminal diol intermediate. Moreover, two types of oxygen species O -OH and O ads originating from the surface hydroxyl and the strongly adsorbed gas-phase O 2 , respectively, play an essential role in defhydrogenating geminal diol to furoic acid. Most importantly, the hydroxyl, O -OH , and O ads consumed on δ-MnO 2 can be reconstructed under reaction conditions. Among the three δ crystal MnO 2 , δ-MnO 2 , with the most abundant hydroxyl and active oxygen species, exhibited the best catalytic performance with 99.53% furfural conversion and nearly 100% furoic acid selectivity. This work identifies the function of hydroxyl and active oxygen species on δ-MnO 2 in furfural oxidation reaction, guiding the design of a non-noble metal catalyst for furoic acid synthesis under base-free conditions. [ABSTRACT FROM AUTHOR]

We report the synthesis of silver-based Janus micromotors that self-propel at 3.5 μm s−1 and speed up to 45 μm s−1 in 0.044 and 1.5 mM of H2O2, respectively, via ionic diffusiophoresis. Morphology optimization further accelerates the speed to 90 μm s−1, which leads to a force of 1 pN and a power of 0.1 fW, similar to biomolecular motors. Their efficiency reaches 10−5, at least two orders of magnitude higher than other chemically-driven micromotors. These micromotors hold great promises in various applications. [ABSTRACT FROM AUTHOR]

Guizhi-Shaoyao-Zhimu decoction (GSZD), a famous ancient oriental Chinese prescription, has been widely used for thousands of years to treat 'arthromyodynia'. The clinical studies of GSZD for the treatment of gout were systematically reviewed to evaluate its clinical efficacy and safety. All randomized controlled trials (RCTs) related to GSZD and gout were collected starting from the database establishment until 29 February 2020, from the Embase, PubMed, Cochrane Library, Web of Knowledge, VIP and other databases. This systematic review and meta-analysis were performed in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, and all analysis of the test was completed using Stata (SE12.0) and Revman (5.3). A total of 535 studies were searched, and 13 studies were included in our meta-analysis (n = 1056 participants). Compared with the conventional western medicine treatments, GSZD treatment yielded a significantly increase in the number of clinically effective patients (OR = 3.67, 95%CI = 2.39–5.64, p = 0.57), an improved mean reduction in the level of uric acid (MD = −54.06; 95% CI = −69.95 to −38.17). Meanwhile, the levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and interleukin-6 (IL-6) were also significantly decreased after the GSZD treatment with no increased relative risk of side-effects. Our present works suggested that GSZD could be considered as an effective alternative remedy for clinical treatment of gout. In addition, it also provides a scientific basis for GSZD to be better applied in clinic in the future. [ABSTRACT FROM AUTHOR]

Objectives: Paeoniflorin, a representative pinane monoterpene glycoside in plants of Paeoniaceae family, possesses promising anticancer activities on diverse tumours. This paper summarized the advance of Paeoniflorin on cancers in vivo and in vitro, discussed the related molecular mechanisms, as well as suggested some perspectives of the future investigations. Key findings: Anticancer activities of paeoniflorin have been comprehensively investigated, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer, glioma, bladder cancer and leukaemia. Furthermore, the potential molecular mechanisms corresponding to the antitumour effects of Paeoniflorin might be related to the following aspects: inhibition of tumour cell proliferation and neovascularization, induction apoptosis, and inhibition of tumour invasion and metastasis. Summary: Paeoniflorin has wide spectrum antitumour activities; however, in vivo and clinical investigations on antitumour effect of Paeoniflorin are lacking which should be focused on further studies. Our present review on antitumour effects of Paeoniflorin would be beneficial for the further molecular mechanisms study, candidate antitumour drug development and clinical research of Paeoniflorin in the future. [ABSTRACT FROM AUTHOR]

Background: Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect. Ganglioside-monosialic acid (GM1) functions as a neuroprotective factor. We assessed the effects of GM1 on the prevention of TIPN in breast cancer patients.Methods: We conducted a randomized, double-blind, placebo-controlled trial including 206 patients with early-stage breast cancer planning to receive taxane-based adjuvant chemotherapy with a follow-up of more than 1 year. Subjects were randomly assigned to receive GM1 (80 mg, day -1 to day 2) or placebo. The primary endpoint was the Functional Assessment of Cancer Treatment Neurotoxicity subscale score after four cycles of chemotherapy. Secondary endpoints included neurotoxicity evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and the Eastern Cooperative Oncology Group neuropathy scale. All statistical tests were two-sided.Results: In 183 evaluable patients, the GM1 group reported better mean Functional Assessment of Cancer Treatment Neurotoxicity subscale scores than patients in the placebo group after four cycles of chemotherapy (43.27, 95% confidence interval [CI] = 43.05 to 43.49 vs 34.34, 95% CI = 33.78 to 34.89; mean difference = 8.96, 95% CI = 8.38 to 9.54, P < .001). Grade 1 or higher peripheral neurotoxicity in Common Terminology Criteria for Adverse Events v4.0 scale was statistically significantly lower in the GM1 group (14.3% vs 100.0%, P < .001). Additionally, the GM1 group had a statistically significantly lower incidence of grade 1 or higher neurotoxicity assessed by Eastern Cooperative Oncology Group neuropathy scale sensory neuropathy (26.4% vs 97.8%, P < .001) and motor neuropathy subscales (20.9% vs 81.5%, P < .001).Conclusions: The treatment with GM1 resulted in a reduction in the severity and incidence of TIPN after four cycles of taxane-containing chemotherapy in patients with breast cancer. [ABSTRACT FROM AUTHOR]

• Reveals that small-sized, high-valence Ru has the highest TOF in the furfural oxidation reaction. • Methanol was used as a probe to verify the evolution of intermediates in furfural oxidation processes. • The Ru's valence state is positively correlated with Ru's TOF. • Using the least amount of Ru (0.25 wt%) and maximizing its gain, the reaction rate was increased by 18 times. δ-MnO 2 exhibits excellent activity for furfural oxidation to furoic acid under base-free conditions. However, its poor C H bond breaking capacity leads to lower conversion efficiency per unit mass catalyst than noble metal. Thus, a series of Ru-modified δ-MnO 2 (Ru x /δ-MnO 2) have been made to enhance its C H bond breaking ability. The result showed that the furfural conversion was greatly enhanced on Ru x /δ-MnO 2 due to the enhanced capability for breaking the C H bond. Especially for Ru0.25/δ-MnO 2 , whose conversion rate per unit mass was 18 times higher than δ-MnO 2. The characterization results showed that the Ru species mainly existed as single atoms or clusters on Ru0.25/δ-MnO 2 and Ru0.5/δ-MnO 2 , while started to aggregate to RuO 2 nanoparticles on Ru1/δ-MnO 2 and Ru2/δ-MnO 2. With the increase of Ru particles, the Ru's average oxidation state (AOS) decreased from +6 on Ru0.25/δ-MnO 2 to +4.74 on Ru2/δ-MnO 2. The Ru's TOF (intrinsic activity per Ru) was positively linearly related to the Ru's AOS. The electron-deficient Ru in Ru0.25/δ-MnO 2 can strongly adsorb the H atom of the C H of geminal diol intermediate and accelerate the breakage of its C H bond. As a result, Ru in the Ru0.25/δ-MnO 2 exhibited the highest TOF, which can even reach 29.85 mmol FF /mmol Ru /h. [Display omitted] [ABSTRACT FROM AUTHOR]

Nucleation and growth of droplets onto seed particles and subsequent solidification is an emerging technique for fabrication of complex colloids with controlled particle morphology and chemical makeup. The technique is often implemented at or near equilibrium, where the final composite particle structure is determined by the equilibrium contact angles of the droplets on the seed particles. Here, we apply the technique out of equilibrium, utilizing the rich and intriguing morphologies emerged as a droplet is triggered to dewet on a rod along the free energy minimization pathway. Specifically, 3-trimethoxysilyl propyl methacrylate (TPM) droplets were nucleated and grown onto silica rods. Upon dewetting, the droplets undergo a series of morphology changes, starting from engulfing the rods, contracting to the center, moving sideways to finally being fully separated from the rods. Composite patchy particles of controlled configurations were achieved by stimulating a fast photopolymerization of the TPM droplets at desired stages of the morphology evolution. Through seed surface functionalization, the patches can be decorated by either the hydroxyl or the amine group, which are used to create fluorescently-patterned patchy particles. Combining with surface evolver simulations, we demonstrate that nonequilibrium solidification of droplets on rods can be used to synthesize two-patch particles with a larger range of control over the patch size than its equilibrium counterpart. Image 1 • Non-equilibrium solidification is applied to synthesize two-patch anisotropic colloidal particles. • The nonequilibrium method offers a wider range of control over the patch size than the prevailing equilibrium counterpart. • Patchy particles with controlled fluorescent patterns are created by selectively labelling different parts of the particles. [ABSTRACT FROM AUTHOR]

Abstract Phosphopantothenoylcysteine (PPC) synthetase (PPCS) catalyzes nucleoside triphosphate-dependent condensation reaction between 4′-phosphopantothenate (PPA) and l -cysteine to form PPC in CoA biosynthesis. The catalytic mechanism of PPCS has not been resolved yet. Coenzyme A biosynthesis protein 2 (Cab2) possesses activity of PPCS in Saccharomyces cerevisiae. Our enzymatic assays suggest that Cab2 could utilize both ATP and CTP to activate PPA in vitro. The results of isothermal titration calorimetry indicate that PPA, CTP, and ATP could bind to Cab2 individually, with PPA having the highest binding affinity. To provide further insight into the catalytic mechanism of Cab2, we determined the crystal structures of Cab2 and its complex with PPA, the reaction intermediate 4′-phosphopantothenoyl-CMP, the final reaction product PPC, and the product analogue phosphopantothenoylcystine. Except for PPA, all other ligands were generated in situ and present in the active-site pocket of Cab2. Structures of Cab2 in complex with ligands provide insight into substrates binding and its catalytic mechanism. Analysis of structures indicates that the carboxyl of PPA-moiety of ligands and the γ-amino group of Asn97 possess different conformations in these complex structures. The cysteine/cystine/serine selectivity assays for Cab2 indicate that the amino group rather than the thiol group of l -cysteine attacks the carbonyl of 4′-phosphopantothenoyl-CMP to form PPC. Based on structural and biochemical data, the catalytic mechanism of Cab2 was proposed for the first time. Graphical Abstract Unlabelled Image Highlights • PPCS catalyzes the formation of PPC from PPA and l -cysteine in CoA biosynthesis. • The catalytic mechanism of PPCS remains unclear. • Cab2 could utilize both ATP and CTP to activate PPA • Both PPA and CTP could bind to Cab2 separately. • The ligands and the residues possess different conformations in complex structures. [ABSTRACT FROM AUTHOR]

[Display omitted] • A binary Type-I In 2 O 3 /Cu-CN heterojunction system was successfully fabricated by hydrothermal method. • After 180 min visible light irradiation, 91% of the BPA molecules were completely degraded. • The degradation ratio for Bisphenol A (BPA) is found 3–5 fold larger than that of solo catalysts of 2D Cu-CN and 3D In 2 O 3. • 3D/2D based In 2 O 3 -Cu-CN, promotes the faster photo-induced charge transfer at heterojunction interface. In this work, a 3D/2D cubic In 2 O 3 /Copper doped graphitic carbon nitride (Cu-CN), heterojunction photocatalysts were synthesized using hydrothermal process and further applied to study its photocatalytic properties for bisphenol-A (BPA) degradation. The cubic three-dimensional In 2 O 3 disperse on the surface of Cu-CN two-dimensional sheet was studied by TEM and XRD. The resulting composites of In 2 O 3 /Cu-CN, show the highest photocatalytic activity for 15%-In 2 O 3 /Cu-CN at optimized ratio under the visible-light irradiation. As compared to both pure Cu-CN and/or In 2 O 3 , the optimized composites of In 2 O 3 /Cu-CN show 5–7 fold improvement for the degradation of BPA. Specifically, In 2 O 3 /Cu-CN with a In 2 O 3 /Cu ratio of 15% displays a kinetic value of 0.01/min, whereas pure Cu-CN and In 2 O 3 have a kinetic value of 0.002/min and 0.0015/min, respectively. The significant enhancement of the photocatalytic behaviour of the heterojunction is attributed to the regulated In 2 O 3 /Cu-CN, that not only promotes the separation of photo-induced electrons and electron-hole efficiently, but also the transformation of heterojunction interface via the band position in between the Cu-CN and In 2 O 3. Furthermore, the improvement mechanism of achievable activity is discussed in details. Moreover, 15%-In 2 O 3 /Cu-CN also exhibits a good stability and photocatalytic activity as verified through four recycling responses. It is evidenced that the superoxide (•O 2 −) and holes (h+) play a crucial role as reactive species for the photocatalytic degradation of BPA. This study provides a new opportunity for the preparation of metal oxide/Cu-CN, heterojunction photocatalysts, which has promising application prospects in wastewater treatment and pollution controlling. [ABSTRACT FROM AUTHOR]

The ‘exterior‑interior relationship between the lung and the large intestine’ is a classical basic theory in Traditional Chinese Medicine. The present study aimed to investigate the roles of the toll like receptor/nuclear factor‑κB (TLR/NF‑κB) signaling pathway in the mutual interactions between the lung and the large intestine. A rat model of allergic asthma complicated with intestinal flora disorder was established by oral administration of Candida albicans and intraperitoneal injection with ovalbumin. The number of inflammatory cells and expression levels immunoglobulin (Ig) E, secretory IgA, interleukin (IL)‑4 and interferon‑γ in serum and bronchoalveolar lavage fluid were subsequently measured. Bacterial colonies and expression of 16S ribosomal DNA were studied in feces samples and pathological alterations of lung tissues were identified. Furthermore, the expression levels of genes associated with the TLR/NF‑κB signaling pathway in the lung and intestinal tissues were determined by reverse transcription‑quantitative polymerase chain reaction. The results of the present study indicated that, in the rat model of allergic asthma complicated with intestinal flora disorder, the expression levels of IL‑4 and IgE, and the numbers of inflammatory cells and C. albicans increased, and marked inflammatory cell infiltration was observed in lung tissues, suggesting that the animal model was successfully established. Furthermore, the present results revealed the mRNA expression levels of genes associated with the TLR/NF‑κB signaling (including myeloid differentiation primary response 88, TNF receptor associated factor 6 and β‑arrestin) were upregulated in both of the lung and intestinal tissues of the model group rats. Collectively, the results demonstrated that the TLR/NF‑κB signaling may serve roles in the mutual interactions between the lung and the large intestine, and TLR and NF‑κB may be potential targets for the treatment of lung diseases complicated with intestinal disorders. [ABSTRACT FROM AUTHOR]

Bi 5 O 7 I belongs to the family of bismuth oxyhalides (BiOX, X = Cl, Br, I), having a unique layered structure with an internal electrostatic field that promotes the separation and transfer of photo-generated charge carriers. Interestingly, Bi 5 O 7 I exhibits higher thermal stability compared to its other BiOX member compounds and absorption spectrum extended to the visible region. Bi 5 O 7 I has demonstrated applications in diverse fields such as photocatalytic degradation of various organic pollutants, marine antifouling, etc. Unfortunately, owing to its wide band gap of ∼2.9 eV, its absorption lies mainly in the ultraviolet region, and a tiny portion of absorption lies in the visible region. Due to limited absorption, the photocatalytic performance of pure Bi 5 O 7 I is still facing challenges. In order to reduce the band gap and increase the light absorption capability of Bi 5 O 7 I, doping and formation of heterostructure strategies have been employed, which showed promising results in the photocatalytic performance. In addition, the plasmonic heterostructures of Bi 5 O 7 I were also developed to further boost the efficiency of Bi 5 O 7 I as a photocatalyst. Here, in this review article, we present such recent efforts made for the advanced development of Bi 5 O 7 I regarding its synthesis, properties and applications. The strategies for photocatalytic performance enhancement have been discussed in detail. Moreover, in the conclusion section, we have presented the current challenges and discussed possible prospective developments in this field. [Display omitted] • Recent progress in Bi 5 O 7 I-based nanocomposites for degradation of organic pollutants. • Synthesis, properties, and photocatalytic applications of Bi 5 O 7 I. • Unique strategies for enhancing photocatalytic performance. • Current challenges, concluding remarks and prospective developments in this field. [ABSTRACT FROM AUTHOR]

Phosphorylated derivatives of phosphatidylinositol (PtdIns), also called phosphoinositides (PIPs), are basic components of membrane-associated signalling systems. A family of PtdIns-transfer proteins (PITPs) called the Sec14 family have been predicted to form a set of functional modules that can sense different types of lipid metabolism and transmit the information to the PIP signalling system. In eukaryotic cells, the Sec14 family exhibits a wide diversity of activity, but the structural basis of this diversity remains unclear. In the present study, the dimeric structure of Sfh3 (Sec14 family homologue 3 in yeast) is reported for the first time and differs from the Sec14 proteins reported to date, all of which are monomeric. Some variations in the binding pocket of Sfh3 were observed and the dimer interface was identified and proposed to provide a link between dimer-monomer state changes and PtdIns binding. Together, these structural changes and the oligomeric state transformation of Sfh3 support ideas of diversity within the Sec14 family and provide some new clues to function. [ABSTRACT FROM AUTHOR]

Abstract: Mannonate dehydratase (ManD; EC4.2.1.8) catalyzes the dehydration of d-mannonate to 2-keto-3-deoxygluconate. It is the third enzyme in the pathway for dissimilation of d-glucuronate to 2-keto-3-deoxygluconate involving in the Entner–Doudoroff pathway in certain bacterial and archaeal species. ManD from Gram negative bacteria has an insert sequence as compared to those from Gram positives revealed by sequence analysis. To evaluate the impact of this insert sequence on the catalytic efficiency, we solved the crystal structures of ManD from Escherichia coli strain K12 and its complex with d-mannonate, which reveal that this insert sequence forms two α helices locating above the active site. The two insert α helices introduce a loop that forms a cap covering the substrate binding pocket, which restricts the tunnels of substrate entering and product releasing from the active site. Site-directed mutations and enzymatic activity assays confirm that the catalytic rate is decreased by this loop. These features are conserved among Gram negative bacteria. Thus, the insert sequence of ManD from Gram negative bacteria acts as a common inducer to decrease the catalytic rate and consequently the glucuronate metabolic rate as compared to those from Gram positives. Moreover, residues essential for substrate to enter the active site were characterized via structural analysis and enzymatic activity assays. [Copyright &y& Elsevier]

Abstract: Glutamate-1-semialdehyde aminotransferase (GSA-AT), also named glutamate-1-semialdehyde aminomutase (GSAM), a pyridoxamine-5′-phosphate (PMP)/pyridoxal-5′-phosphate (PLP) dependent enzyme, catalyses the transamination of the substrate glutamate-1-semialdehyde (GSA) to the product 5-Aminolevulinic acid (ALA) by an unusual intramolecular exchange of amino and oxo groups within the catalytic intermediate 4,5-diaminovalerate (DAVA). This paper presents the crystal structure of GSA-AT from Bacillus subtilis (GSA-AT Bsu ) in its PMP-bound form at 2.3Å resolution. The structure was determined by molecular replacement using the Synechococcus GSAM (GSAMSyn) structure as a search model. Unlike the previous reported GSAM/GSA-AT structures, GSA-AT Bsu is a symmetric homodimer in the PMP-bound form, which shows the structural symmetry at the gating loop region with open state, as well as identical cofactor (PMP) binding in each monomer. This observation of PMP in combination with an “open” lid supports one characteristic feature for this enzyme, as the catalyzed reaction is believed to be initiated by PMP. Furthermore, the symmetry of GSA-AT Bsu structure challenges the previously proposed negative cooperativity between monomers of this enzyme. [Copyright &y& Elsevier]

Abstract: Yeast poly(U)-binding protein (Pub1) is a major nuclear and cytoplasmic protein that contains three RNA recognition motif (RRM) domains (termed Pub1RRM1, Pub1RRM2 and Pub1RRM3). Pub1 has been implicated as a regulator of cellular mRNA decay. Nearly 10% of all yeast mRNA decay occurs in a Pub1-dependent manner. Pub1 binds to and stabilizes AU-rich element (ARE) and ARE-like sequence-containing transcripts by protecting them from degradation through the deadenylation-dependent pathway, and also binds to and stabilizes stabilizer element (STE)-containing transcripts by preventing their degradation via the nonsense-mediated decay (NMD) pathway. RNA-binding analyses showed that Pub1 binds to poly(U) in vitro. Here we show the crystal structures of Pub1RRM2 and the first two tandem RRM domains (Pub1RRM12). Crystallography showed that the structure of Pub1RRM12 is a domain-swapped dimer. Size exclusion chromatography assay and analytical ultracentrifugation (AUC) showed that Pub1RRM12 is a monomer in solution. Kinetic analysis showed that all three individual RRM domains can bind to poly(U) with similar affinities and Pub1RRM12 binds to a long poly(U) segment with higher affinity. Mutagenesis analysis revealed that residues on the β-sheets of Pub1RRM1 and Pub1RRM2 are critical for poly(U) binding. [ABSTRACT FROM AUTHOR]