Deleterious synonymous mutation identification based on selective ensemble strategy.

Although previous studies have revealed that synonymous mutations contribute to various human diseases, distinguishing deleterious synonymous mutations from benign ones is still a challenge in medical genomics. Recently, computational tools have been introduced to predict the harmfulness of synonymous mutations. However, most of these computational tools rely on balanced training sets without considering abundant negative samples that could result in deficient performance. In this study, we propose a computational model that uses a selective ensemble to predict deleterious synonymous mutations (seDSM). We construct several candidate base classifiers for the ensemble using balanced training subsets randomly sampled from the imbalanced benchmark training sets. The diversity measures of the base classifiers are calculated by the pairwise diversity metrics, and the classifiers with the highest diversities are selected for integration using soft voting for synonymous mutation prediction. We also design two strategies for filling in missing values in the imbalanced dataset and constructing models using different pairwise diversity metrics. The experimental results show that a selective ensemble based on double fault with the ensemble strategy EKNNI for filling in missing values is the most effective scheme. Finally, using 40-dimensional biology features, we propose a novel model based on a selective ensemble for predicting deleterious synonymous mutations (seDSM). seDSM outperformed other state-of-the-art methods on the independent test sets according to multiple evaluation indicators, indicating that it has an outstanding predictive performance for deleterious synonymous mutations. We hope that seDSM will be useful for studying deleterious synonymous mutations and advancing our understanding of synonymous mutations. The source code of seDSM is freely accessible at https://github.com/xialab-ahu/seDSM.git.

Effects of slow-release nitrogen and urea combined application on soil physicochemical properties and fungal community under total straw returning condition.

Under the system of full straw returning, the relationship between soil fungal community diversity and soil physiochemical properties, and the combined application of slow-release nitrogen and urea is unclear. To evaluate its effect and provide an effective strategy for sustainable agricultural production, a 2-year field positioning trial was conducted using maize as the research object. The experiment was designed with two factors: straw treatment(S) and nitrogen fertilizer treatment(N),Six experimental treatments were set up,S1N0,S1N1,S1N2,S1N3,S1N4,S0N2,respectively.Analysis of 54 soil samples revealed 15 fungal phyla and 49 fungal classes. The composition of fungal communities in each treatment was basically the same, but there were significant differences in species abundance. Under total straw returning conditions, the combined application of slow-release nitrogen fertilizer and normal nitrogen fertilizer significantly increased the relative abundance of Ascomycota. During the jointing stage, tasseling stage and maturity stage, S1N4, S1N3 and S1N2 increased by 25.76%, 22.97%, 20.74%; 25.11%, 30.02%, 23.64% and 22.47%, 28.14%, 22.71% respectively compared with S0N2.The relative abundance of Basidiomycota was significantly reduced. Alpha diversity analysis showed that the straw returning mode significantly increased the Shannon index and decreased the Simpson index, which was obvious in the jointing stage and tasseling stage. The principal coordinate analysis analysis results showed that the fungal communities formed different clusters in the horizontal and vertical directions at the three growth stages of corn jointing, tasseling and maturity. At the jointing stage and tasseling stage, the communities of the straw return treatment and the straw removal treatment were separated, and the community distribution of each treatment was not significantly different in the mature stage. Total straw returning combined with slow-release fertilizer significantly (P＜0.05) increased the soil organic carbon, nitrate nitrogen and ammonia nitrogen content in each growth period, and increased the soil total nitrogen and hydrolyzable nitrogen content (P＞0.05).After the straw was returned to the field, the combined application of slow-release nitrogen fertilizer and common urea had a significant impact on soil urease, catalase, and sucrase activities. Among them, the three enzyme activities were the highest in the S1N3 treatment at the jointing stage and maturity stage, and the S1N4 treatment at the tasseling stage had the highest enzyme activity. Fungal community composition is closely related to environmental factors. Soil organic carbon, urease and catalase are positively correlated with Ascomycota and negatively correlated with Basidiomycota.

Optimizing the Spatial Density of Single Co Sites via Molecular Spacing for Facilitating Sustainable Water Oxidation.

Advances in single-atom (-site) catalysts (SACs) provide a new solution of atomic economy and accuracy for designing efficient electrocatalysts. In addition to a precise local coordination environment, controllable spatial active structure and tolerance under harsh operating conditions remain great challenges in the development of SACs. Here, we show a series of molecule-spaced SACs (msSACs) using different acid anhydrides to regulate the spatial density of discrete metal phthalocyanines with single Co sites, which significantly improve the effective active-site numbers and mass transfer, enabling one of the msSACs connected by pyromellitic dianhydride to exhibit an outstanding mass activity of (1.63 ± 0.01) × 105 A·g-1 and TOFbulk of 27.66 ± 1.59 s-1 at 1.58 V (vs RHE) and long-term durability at an ultrahigh current density of 2.0 A·cm-2 under industrial conditions for oxygen evolution reaction. This study demonstrates that the accessible spatial density of single atom sites can be another important parameter to enhance the overall performance of catalysts.

Complete genome sequencing and comparative genome analysis of the extremely halophilic archaea, Haloterrigena daqingensis.

In the present study, we report the complete genome sequencing of Haloterrigena daqingensis species. The genome of H. daqingensis JX313T consisted of a circular chromosome with three plasmids. The genome size and G+C content were estimated to be 3835796 bp and 61.7%, respectively. A total of 4158 genes were predicted with six rRNAs and 45 tRNAs. Metabolic pathway analysis suggests that H. daqingensis JX313T codes for all the necessary genes responsible to sustain its life at saline environment. The pan-genome analysis suggests that the number of singleton-gene between H. daqingensis and other Haloterrigena species varied. The study not only helps us understand H. daqingensis strategy for dealing with high stress, but it also provides an overview of its genomic makeup.

Integrated Design of Interlayer/Current-Collector: Heteronanowires Decorated Carbon Microtube Fabric for High-Loading and Lean-Electrolyte Lithium-Sulfur Batteries.

Low sulfur loading, high electrolyte/sulfur (E/S) ratio, and sluggish sulfur redox reaction are the main challenges that severely impede the practical application of lithium-sulfur batteries (LSBs). To address these problems, a self-standing hollow carbonized cotton cloth (CCC) decorated with TiO2 -TiN heteronanowires (CCC@TiO2 -TiN) is proposed to replace the traditional cathode. Concretely, one side of CCC@TiO2 -TiN serves as a current-collector to load sulfur (CCC@TiO2 -TiN/S), while the other side facing the separator acts as interlayer to inhibit shuttle effect. This advanced intergrated interlayer/current-collector cathode is endowed with excellent 3D electron/ion transportation, a strong confinement barrier, and vast sulfur loading sites. Moreover, the as-developed TiO2 -TiN heteronanowires work as in situ capture and catalysis sites for the reversible and accelerated sulfur redox reaction. Therefore, the intergrated cathode of CCC@TiO2 -TiN/S achieves an ultrahigh sulfur loading of 13 mg cm-2 and delivers a superb areal capacity of 9.09 mAh cm-2 under the ultralow E/S ratio of 4.6 µL mg-1 . This work provides a new model material to achieve high sulfur loading and lean-electrolyte toward the practical LSBs with high specific energy density.

GM-CSF enhanced the effect of CHOP and R-CHOP on inhibiting diffuse large B-cell lymphoma progression via influencing the macrophage polarization.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common type of the Non-Hodgkin lymphomas (NHLs) formed by the neoplastic transformation of mature B cells. As the first-line therapeutics, CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and R-CHOP (Rituximab + CHOP), either using alone or in combination with GM-CSF, have achieved great efficacy in DLBCL patients. However, the underlying mechanisms are still largely unknown. METHODS: In the present study, the combination use of CHOP and R-CHOP with GM-CSF was used to evaluate their effects on the tumor immune microenvironment of DLBCL. CHOP and R-CHOP administration was found to inhibit the growth and metastasis of DLBCL, with a higher efficacy in R-CHOP-challenged DLBCL mice. The anti-tumor effect of CHOP and R-CHOP was further amplified by GM-CSF. RESULTS: CHOP and R-CHOP therapeutics potentiated the anti-tumor properties of macrophages, as evidenced by the increased M1 macrophage and the decreased M2 macrophage accumulation in DLBCL-bearing mice. In a co-culture system, macrophages primed with CHOP and R-CHOP therapeutics inhibited multiple malignant behaviors of DLCBL cells. Mechanistically, CHOP/R-CHOP suppressed the activation of AKT signaling. These anti-tumor effects of CHOP/R-CHOP were all augmented by GM-CSF. CONCLUSIONS: Our work provided new insights into the immune-regulatory roles of CHOP and R-CHOP in the treatment of DLBCL, as well as the synergistic effects of GM-CSF in CHOP and R-CHOP therapeutics. Although our results suggest the synergistic effect of GM-CSF on DLBCL already sensitive to CHOP and R-CHOP, however, future studies are warranted to explore the role of GM-CSF on R-CHOP-resistant DLBCL. Trial registration Not applicable.

Synthesis and biological evaluation of novel ligustrazine-chalcone derivatives as potential anti-triple negative breast cancer agents.

A series of novel ligustrazine-chalcone hybrids were synthesized and evaluated for their in vitro and in vivo antitumor activities. The results showed that most of these compounds exhibited significant in vitro cytotoxicity against MDA-MB-231, MCF-7, A549 and HepG2 cell lines with IC50 values as low as sub-micromole. Among them, compounds 6c and 6f possessed better comprehensive characteristics for the antiproliferation effects on both MDA-MB-231 (IC50: 6c, 1.60 ± 0.21 µM; 6f, 1.67 ± 1.25 µM) and MCF-7 (IC50: 6c, 1.41 ± 0.23 µM; 6f, 1.54 ± 0.30 µM). They also exhibited the potent colony-formation inhibitory abilities on above two cell lines in both concentration and time dependent manners, as well as the significantly suppression capabilities against the migration of such cell lines in a concentration dependent manner by wound-healing assay. Of note, compound 6c could significantly induce the apoptosis of MDA-MB-231 cells in a concentration dependent manner and inhibited the transformation of the growth cycle of MDA-MB-231 cells and blocked the cell growth cycle in G0/G1 phase. Moreover, the in vivo antiproliferation assay of compound 6c on TNBC model indicated such compound had a remarkable potency against tumor growth with a widely safety window. Further immunohistochemistry analysis illustrated that compound 6c was provided with a potent capacity to significantly reduce the Ki-67 positive rate in a dose dependent manner. All the results suggested that these hybrids presented both in vitro and in vivo proliferation inhibition potency against breast cancer and further development with good therapeutic potential should be of great interest.

Design, synthesis and antitumor evaluation of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives as potential c-Met inhibitors.

A series of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives (10a-10x) were designed, synthesized, and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against the SH-SY5Y, MDA-MB-231, A549, and HepG2 cell lines. Most of the compounds remarkably inhibited c-Met kinase and showed moderate to good cytotoxicity and selectivity toward the four cancer cell lines. Among them, compounds 10b and 10f were the two most potent selective c-Met inhibitors with half-maximal inhibitory concentration (IC50) values of 5.17 ± 0.48 nM and 5.62 ± 0.78 nM, respectively, and suppression abilities comparable with the positive control cabozantinib. Cell proliferation assay further demonstrated that the two most promising compounds 10a and 10b also showed good cytotoxicity and selectivity toward MDA-MB-231 cells, with IC50 values of 26.67 ± 2.56 µM and 26.83 ± 2.41 µM, respectively. Compounds 10f and 10g showed cytotoxicity and selectivity toward A549 cells, with IC50 values of 20.20 ± 2.04 µM and 21.65 ± 1.58 µM, respectively. All antiproliferative activities were within the range of those of cabozantinib. Notably, these compounds presented relatively low hepatotoxicity compared with reference drugs. Moreover, the preliminary structure-activity relationship and docking studies revealed that replacement of a nitrogen-containing heterocycle on the R2 (block A) group might improve the c-Met kinase inhibitory and antiproliferative effects in MDA-MB-231 cells, whereas displacement by a substituted benzene ring, especially for the p-fluorophenyl or 4-fluoro-3-methoxyphenyl moiety, on the R2 group enhanced cytotoxicity toward A549 cells. Together, these results suggest that 10b and 10f are promising compounds and provide a basis for their development as new antitumor agents.

Cryogen adaptive and integrated differential pressure sensor for level sensing based on an optical Fabry-Perot interferometer.

In this paper, we introduce a cryogen-adaptive sensor based on a micro-electromechanical system (MEMS) for level measurement of cryogenic fluids. The sensor is fabricated by an optical fiber inserted in a glass ferrule and an integrated Fabry-Perot (FP) chip using the MEMS technique. We carried a liquid nitrogen level measurement experiment to verify the performance of the sensor and a low coherent interference system is used to transform the liquid level to absolute phase. The measuring range is 24 cm and can be expanded more widely. The experimental results show that the sensor has a good monotonic linear response (coefficient determination ${{\rm R}^2} \gt {0.998}$R2>0.998), and the measurement error is less than ${ \pm 5}\;{\rm mm}$±5mm in liquid nitrogen. The excellent cryogenic temperature performance from $ - {260}^\circ {\rm C}$-260∘C to $ - {100}^\circ {\rm C}$-100∘C also is demonstrated, which shows the potential application in level measurement of various cryogenic liquids.

Generating Time-Series LAI Estimates of Maize Using Combined Methods Based on Multispectral UAV Observations and WOFOST Model.

Green leaf area index (LAI) is an important variable related to crop growth. Accurate and timely information on LAI is essential for developing suitable field management strategies to mitigate risk and boost yield. Several remote sensing (RS) based methods have been recently developed to estimate LAI at the regional scale. However, the performance of these methods tends to be affected by the quality of RS data, especially when time-series LAI are required. For crop LAI estimation, supplementary growth information from crop model is helpful to address this issue. In this study, we focus on the regional-scale LAI estimations of spring maize for the entire growth season. Using time-series multispectral RS data acquired by an unmanned aerial vehicle (UAV) and the World Food Studies (WOFOST) crop model, three methods were applied at different crop growth stages: empirical method using vegetation index (VI), data assimilation method and hybrid method. The VI-based method and assimilation method were used to generate time-series LAI estimations for the whole crop growth season. Then, a hybrid method specially for the late-stage LAI retrieval was developed by integrating WOFOST model and data assimilation. Using field-collected LAI data in Hongxing Farm in 2014, the performances of these three methods were evaluated. At the early stage, the VI-based method (R2 = 0.63, RMSE = 0.16, n = 36) achieved higher accuracy than the assimilation method (R2 = 0.54, RMSE = 0.52, n = 36), whereas at the mid stage, the assimilation method (R2 = 0.63, RMSE = 0.46, n = 28) showed higher accuracy than the VI-based method (R2 = 0.41, RMSE = 0.51, n = 28). At the late stage, the hybrid method yielded the highest accuracy (R2 = 0.63, RMSE = 0.46, n = 29), compared with the VI-based method (R2 = 0.19, RMSE = 0.43, n = 28) and the assimilation method (R2 = 0.20, RMSE = 0.44, n = 29). Based on the results above, we considered a combination of the three methods, i.e., the VI-based method for the early stage, the assimilation method for the mid stage, and the hybrid method for the late stage, as an ideal strategy for spring-maize LAI estimation for the entire growth season of 2014 in Hongxing Farm, and the accuracy of the combined method over the whole growth season is higher than that of any single method.

Tripartite motif-containing 37 (TRIM37) promotes the aggressiveness of non-small-cell lung cancer cells by activating the NF-κB pathway.

Non-small-cell lung cancer (NSCLC), in which the NF-κB pathway is constitutively activated, is one of the most common malignancies. Herein, we identify an E3 ubiquitin ligase, tripartite motif-containing 37 (TRIM37), participating in the K63 polyubiquitination of TRAF2, which is a significant step in the activation of NF-κB signaling. Both the mRNA and the protein expression levels of TRIM37 were much higher in NSCLC cell lines and tissues than in normal bronchial epithelial cells and matched adjacent non-tumor tissues. TRIM37 expression correlated closely with clinical stage and poor survival in NSCLC. Overexpression of TRIM37 antagonized cisplatin-induced apoptosis, induced angiogenesis and proliferation, and increased the aggressiveness of NSCLC cells in vitro and in vivo, whereas inhibition of TRIM37 led to the opposite effects. Gene set enrichment analysis (GSEA) showed that TRIM37 expression significantly correlated with NF-κB signaling. Furthermore, we found that TRIM37 bound to TRAF2 and promoted K63-linked ubiquitination of TRAF2, sustaining the eventual activation of the NF-κB pathway. Mutation in the ring finger domain of TRIM37, a hallmark of E3 ubiquitin ligases, led to loss of the ability to promote K63 polyubiquitination of TRAF2 and activate NF-κB signaling. Taken together, our findings provide evidence that TRIM37 plays an important role in constitutive NF-κB pathway activation and could serve as a prognostic factor and therapeutic target in NSCLC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Study on Synthesis and Biological Evaluation of 3-Aryl Substituted Xanthone Derivatives as Novel and Potent Tyrosinase Inhibitors.

Tyrosinase plays a key role in the melanin biosynthesis since it catalyzes the transformation of tyrosine into L-dopaquinone. A large number of studies have also shown that molecules to efficiently inhibit the activity of tyrosinase would be potentially used in treating many depigmentation-related disorders. In this study, we targeted a series of structure-based 3-aryl substituted xanthone derivatives in which diverse functional groups were respectively attached on 3-aromatic ring moiety as new tyrosinase inhibitors. The results demonstrated that all obtained compounds had potent tyrosinase inhibitory activities with IC50 values at micromolar range. Especially, compound 4t was found to be the most active tyrosinase inhibitor with the IC50 value of 11.3 µM, uncovering that the introduction of the proper hydroxyl group in the 3-aromatic ring was beneficial for enhancing the inhibitory potency against tyrosinase. Moreover, the inhibition mechanism and inhibition kinetics studies revealed that compound 4t presented such inhibitory effect by acting as the reversible and competitive-uncompetitive mixed-II type inhibitor. Further molecular docking simulation showed that 3-aromatic ring of compound 4t was inserted into the narrow regions of binuclear copper-binding site at the bottom of the enzyme binding pocket, while the xanthone skeleton was positioned at the surface of tyrosinase. Taken together, these data suggested that such type of molecules might be utilized for the development of new and promising candidate for the treatment of depigmentation-related disorders.

Design of Sparse FIR Decision Feedback Equalizers in MIMO Systems Using Hybrid l1/l2 Norm Minimization and the OMP Algorithm.

In this paper, a novel scheme using hybrid l1/l2 norm minimization and the orthogonal matching pursuit (OMP) algorithm is proposed to design the sparse finite impulse response (FIR) decision feedback equalizers (DFE) in multiple input multiple output (MIMO) systems. To reduce the number of nonzero taps for the FIR DFE while ensuring its design accuracy, the problem of designing a sparse FIR DFE is transformed into an l0 norm minimization problem, and then the proposed scheme is used to obtain the sparse solution. In the proposed scheme, a sequence of minimum weighted l2 norm problems is solved using the OMP algorithm. The nonzero taps positions can be corrected with the different weights in the diagonal weighting matrix which is computed through the hybrid l1/l2 norm minimization. The simulation results verify that the sparse FIR MIMO DFEs designed by the proposed scheme get a significant reduction in the number of nonzero taps with a small performance loss compared to the non-sparse optimum DFE under the minimum mean square error (MMSE) criterion. In addition, the proposed scheme provides better design accuracy than the OMP algorithm with the same sparsity level.

Synthesis and Evaluation of Novel Ligustrazine Derivatives as Multi-Targeted Inhibitors for the Treatment of Alzheimer's Disease.

A series of novel ligustrazine derivatives 8a⁻r were designed, synthesized, and evaluated as multi-targeted inhibitors for anti-Alzheimer's disease (AD) drug discovery. The results showed that most of them exhibited a potent ability to inhibit both ChEs, with a high selectivity towards AChE. In particular, compounds 8q and 8r had the greatest inhibitory abilities for AChE, with IC50 values of 1.39 and 0.25 nM, respectively, and the highest selectivity towards AChE (for 8q, IC50 BuChE/IC50 AChE = 2.91 × 106; for 8r, IC50 BuChE/IC50 AChE = 1.32 × 107). Of note, 8q and 8r also presented potent inhibitory activities against Aß aggregation, with IC50 values of 17.36 µM and 49.14 µM, respectively. Further cellular experiments demonstrated that the potent compounds 8q and 8r had no obvious cytotoxicity in either HepG2 cells or SH-SY5Y cells, even at a high concentration of 500 µM. Besides, a combined Lineweaver-Burk plot and molecular docking study revealed that these compounds might act as mixed-type inhibitors to exhibit such effects via selectively targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChEs. Taken together, these results suggested that further development of these compounds should be of great interest.

[Recurrence of Cerebral Infarction Associated Aspirin Resistance or Chinese Medical Constitutions: a Correlation Study].

OBJECTIVE: To explore the correlation between the recurrence of cerebral infarction and aspirin resistance (AR)/Chinese medical (CM) constitutions. METHODS: Totally 413 cerebral infarction patients took Aspirin Enteric-coated Tablet (100 mg per day) while receiving routine therapy, 5 days at least in a week. They were followed-up for 12 months. Aspirin sensitivity (AS) was determined using turbidimetry. CM constitutions among patients with different AS were compared. Ratios of AR patients and AS patients of different CM constitutions in cerebral infarction recurrent patients were compared. Platelet membrane glycoproteins (GP) II b HPA-3 gene polymorphism was detected by polymerase chain reaction (PCR) method. Correlation between recurrence of cerebral infarction and AR, bb genotypes, CM constitutions times AS were analyzed by Logistic regression. RESULTS: Totally 11 patients dropped out, 101 (25.12%)with recurrent cerebral infarction and 301 (74.88%) without recurrent cerebral infarction. There were 152 (37.81%) AR patients and 250 (62.19%) AS patients. AR accounted for 26.6% (80/ 301) and AS accounted for 73.4% (221/301) in non-recurrent cerebral infarction patients. AR accounted for 71.3% (72/101) and AS accounted for 28.7% (29/101) in recurrent cerebral infarction patients. There was statistical difference in AR and AS ratios (χ2 = 64.287, P = 0.000). The proportion of yin deficiency constitution (YDC) was the largest [28.3% (43/152)] in AR patients. The proportion of blood stasis constitution (BSC) was the largest [23.6% (59/250)] in AS patients. There was statistical difference in CM constitutions between AR patients and AS patients (χ2 = 21.574, P < 0.01). The former 4 recurrent rates occurred in AR patients of YDC, BSC, damp-phlegm constitution (DPC), qi deficiency constitution (QDC). YDC occupied the first place [22.4% (34/152)]. The former 4 recurrent rates occurred in AS patients of BSC, QDC, DPC, damp-heat constitution (DHC). BSC occupied the first place [3.2% (2/250)]. Compared with non-recurrent cerebral infarction patients and AS patients, bb gene occurred most often, but aa gene and ab gene occurred obviously lesser in non-recurrent cerebral infarction patients and AR patients (χ2 = 20.171, χ2 = 55.139, P < 0.01). AR and bb gene were positively correlated with recurrent cerebral infarction (OR = 18.423, P = 0.000; OR = 1.304, P = 0.028). Body constitutions interacted with AS (OR = 0.707, P = 0.000). CONCLUSIONS: Recurrent cerebral infarction was closely related to AR and constitutional types. The recurrence rate was higher in AR patients of YDC. GP I b HPA-3 bb genotype might be a risk factor for AR and recurrent cerebral infarction.

Tomensides A-D, new antiproliferative phenylpropanoid sucrose esters from Prunus tomentosa leaves.

To search for novel cytotoxic constituents against cancer cells as lead structures for drug development, four new 3-phenylpropanoid-triacetyl sucrose esters, named tomensides A-D (1-4), and three known analogs (5-7) were isolated from the leaves of Prunus tomentosa. Their structures were elucidated by spectroscopic analyses (1D, 2D NMR, CD and HRESIMS). The cytotoxic activities of all isolates against four human cancer cell lines (MCF-7, A549, HeLa and HT-29) were assayed, and the results showed that these isolates displayed stronger inhibitory activities compared with positive control 5-fluorouracil. Tomenside A (1) was the most active compound with IC50 values of 0.11-0.62 µM against the four tested cell lines. The structure-activity relationship (SAR) of the isolates was also discussed. The primary screening results indicated that these 3-phenylpropanoid-triacetyl sucrose esters might be valuable source for new potent anticancer drug candidates.

Antioxidant and tyrosinase inhibitory effects of neolignan glycosides from Crataegus pinnatifida seeds.

In our efforts to find an inhibitor of melanin formation and develop potential depigmenting agents for skin-protecting cosmetics and medicinal products from natural resources, we focused on the seeds of Crataegus pinnatifida which showed antioxidant and tyrosinase-inhibiting activities. By activity-guided fractionation of an extract of C. pinnatifida seeds, four new neolignan glycosides, pinnatifidaninsides A-D (1-4), along with two known compounds (5-6), were isolated. Their structures were elucidated by spectroscopic analyses, especially 1D, 2D NMR and CD spectra. The antioxidant and tyrosinase-inhibiting activities of all isolates were assayed. Compound 6 showed good activity against 2,2-diphenyl-1-pikrylhydrazyl, while compounds 1, 2, 5, and 6 exhibited strong 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) free radical scavenging activity, being as effective as, or even more effective than the positive control Trolox. Moreover, compounds 5 and 6 displayed a moderate mushroom tyrosinase inhibitory activity.

An aqueous alkaline zinc-sulfur flow battery.

We demonstrate a rechargeable aqueous alkaline zinc-sulfur flow battery that comprises environmental materials zinc and sulfur as negative and positive active species. Meanwhile, a nickel-based electrode is also obtained by a two-step process to decrease the polarization of the sulfur redox reaction, thus greatly improving the voltage efficiency of the system from 32% to 78% at 10 mA cm-2.

Incidence, clinical features, and risk factors of hemocoagulase-induced hypofibrinogenemia: A retrospective real-world study.

The objective of this study was to explore the real-world incidence, severity, clinical features, and potential risk factors associated with hypofibrinogenemia induced by hemocoagulase. Based on Chinese Hospital Pharmacovigilance System, a retrospective case-control study was conducted, enrolling hospitalized patients who received hemocoagulase for the treatment or prevention of hemorrhage in Weifang People's Hospital in China from January 2021 to May 2022. Univariate and multivariate logistic regression was performed to analyze the potential risk factors. Out of 10,397 hospitalized patients who received hemocoagulase, 341 patients showed positive triggers, with 235 patients ultimately conformed as hemocoagulase-associated hypofibrinogenemia. The system positive alarm rate was 68.91%, and the overall incidence of hemocoagulase-induced hypofibrinogenemia was 2.26%, predominantly characterized by mild to moderate severity levels. The incidence varied among the 4 types of hemocoagulase, with the highest incidence observed in hemocoagulase Agkistrodon Halys Pallas at 4.59%. The incidence of hemocoagulase from Deinagkistrodon acutus, Bothrops Atrox and Adder were 0.97%, 0.44% and 0.12%, respectively. Multivariate logistic regression analysis revealed that age (odds ratios [OR] = 177.328, P < .001), source of snake venom (OR = 5.641, P < .05), albumin (OR = 2.487, P < .001), and cumulative dosage (OR = 1.106, P < .001) were independent risk factors. Increased risk of hemocoagulase-related hypofibrinogenemia may be associated with children, elderly patients, low albumin levels, high cumulative doses and hemocoagulase from Agkistrodon Halys Pallas. Early recognition and close drug monitoring for these high-risk patients are vital in clinical practice.

An optimal combined slow-release nitrogen fertilizer and urea can enhance the decomposition rate of straw and the yield of maize by improving soil bacterial community and structure under full straw returning system.

Under a full straw returning system, the relationship between soil bacterial community diversity and straw decomposition, yield, and the combined application of slow-release nitrogen and urea remains unclear. To evaluate these effects and provide an effective strategy for sustainable agricultural production, a 2-year field positioning trial was conducted using maize as the research object. Six experimental treatments were set up: straw returning + no nitrogen fertilizer (S1N0), straw returning + slow-release nitrogen fertilizer:urea = 0:100% (S1N1), straw returning + slow-release nitrogen fertilizer:urea = 30%:70% (S1N2), straw returning + slow-release nitrogen fertilizer:urea = 60%:40% (S1N3), straw returning + slow-release nitrogen fertilizer:urea = 90%:10% (S1N4), and straw removal + slow-release nitrogen fertilizer:urea = 30%:70% (S0N2). Significant differences (p < 0.05) were observed between treatments for Proteobacteria, Acidobacteriota, Myxococcota, and Actinobacteriota at the jointing stage; Proteobacteria, Acidobacteriota, Myxococcota, Bacteroidota, and Gemmatimonadota at the tasseling stage; and Bacteroidota, Firmicutes, Myxococcota, Methylomirabilota, and Proteobacteria at the maturity stage. The alpha diversity analysis of the soil bacterial community showed that the number of operational taxonomic units (OTUs) and the Chao1 index were higher in S1N2, S1N3, and S1N4 compared with S0N2 at each growth stage. Additionally, the alpha diversity measures were higher in S1N3 and S1N4 compared with S1N2. The beta diversity analysis of the soil bacterial community showed that the bacterial communities in S1N3 and S1N4 were more similar or closely clustered together, while S0N2 was further from all treatments across the three growth stages. The cumulative straw decomposition rate was tested for each treatment, and data showed that S1N3 (90.58%) had the highest decomposition rate. At the phylum level, straw decomposition was positively correlated with Proteobacteria, Actinobacteriota, Myxococcota, and Bacteroidota but significantly negatively correlated with Acidobacteriota. PICRUSt2 function prediction results show that the relative abundance of bacteria in soil samples from each treatment differed significantly. The maize yield of S1N3 was 15597.85 ± 1477.17 kg/hm2, which was 12.80 and 4.18% higher than that of S1N1 and S0N2, respectively. In conclusion, a combination of slow-release nitrogen fertilizer and urea can enhance the straw decomposition rate and maize yield by improving the soil bacterial community and structure within a full straw returning system.