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The screening and identification of drug metabolites in biological matrices is challenging, and ultra-high performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) has become a powerful technological tool for drug metabolites analysis due to its high sensitivity. However, the spectral information contained in existing chemical standards and databases is very limited, and the UHPLC-Q-Exactive Orbitrap MS technique alone cannot satisfy the identification of complex and diverse metabolites. Therefore, there is an urgent need for a new strategy to achieve comprehensive drug metabolic profile. Based on this, we have innovatively constructed a “recursive tree” analysis strategy and bridged it with network pharmacology for elucidating the pharmacological mechanisms of drugs. In this paper, we investigated the overall metabolic profile of formononetin as an example and utilized the primary branching metabolites of formononetin as effective ingredients for the study of the anti-NAFLD mechanism. The results showed that a total of 131 metabolites (prototype drug included) were detected and identified. Among them, 106 metabolites were found in rats and 31 metabolites were found in liver microsomes. Glucose conjugation, demethylation, sulfation, glucuronidation, and their complex reactions were the major processes of formononetin biotransformation. Network pharmacology results screened 104 potential targets and 20 major signaling pathways. Their mechanisms may be additive and/or synergistic effects. In addition, the therapeutic effects of formononetin against NAFLD were investigated based on palmitic acid / oleic acid-induced HepG2 cells. In summary, the recursive tree analysis strategy provides a convenient method for the identification of metabolites, and its seamless integration with network pharmacology lays the foundation for studying the pharmacological activities of natural products.

Particle damping technology is applied in vibration and noise reduction because of its good broadband vibration reduction effect. The energy transfer and loss between particles are keys to the role of damping. This paper investigates the relationship between the thermal energy dissipation caused by the collision of particles and the input energy. The temperature rise characteristics under different vibration states are studied. The results show significant differences in the thermal dissipation characteristics of granular assemblies for different vibration states. Under equivalent excitation amplitudes, the frequency increases, and the thermal loss of the particles increases. At the same frequency, the excitation amplitudes increase, and the thermal loss of the particles decreases. Granular assemblies in strong vibrational states, such as a gas-like state, have intense vibrations and apparent temperature-increasing effects. However, in this vibration state, the input energy to the particles is considerable, and the thermal loss accounts for a small proportion of the total energy. In states such as solid-like states, micro-vibrational states, and intermediate vibrational states, the particles interact closely, and the input energy for the particles is small. Additionally, the movement of the particles is not intense, and the thermal loss accounts for a large proportion of the total energy. The thermal loss of the particles also shows a frequency variation characteristic. According to the different temperature rise characteristics of the particles, the proportion of thermal energy consumption is analyzed. The research shows that the proportion of thermal energy consumption is not more than 70%, so there are other forms of energy consumption in the vibration reduction and energy consumption of the particles.

Heteroatom doping has emerged as a prevailing strategy to enhance the storage of sodium ions in carbon materials. However, the underlying mechanism governing the performance enhancement remains undisclosed. Herein, we fabricated N/S co-doped carbon beaded fibers (S-N-CBFs), which exhibited glorious rate performance and durableness in Na+ storage, showcasing no obvious capacity decay even after 3500 cycles. Furthermore, when used as anodes in sodium-ion capacitors, the S-N-CBFs delivered exceptional results, boasting a high energy density of 225 Wh·kg–1, superior power output of 22500 W·kg–1, and outstanding cycling stability with a capacity attenuation of merely 0.014% per cycle after 4000 cycles at 2 A·g–1. Mechanistic investigations revealed that the incorporation of both pyridinic N and pyrrolic N into the carbon matrix of S-N-CBFs induced internal electric fields (IEFs), with the former IEF being stronger than the latter, in conjunction with the doped S atom. Density functional theory calculations further unveiled that the intensity of the IEF directly influenced the adsorption of Na+, thereby resulting in the exceptional performances of S-N-CBFs as sodium-ion storage materials. This work uncovers the pivotal role of IEF in regulating the electronic structure of carbon materials and enhancing their Na+ storage capabilities, providing valuable insights for the development of more advanced electrode materials.

Trueperella pyogenes is an important opportunistic pathogenic bacterium widely distributed in the environment. Pyolysin (PLO) is a primary virulence factor of T. pyogenes and capable of lysing many different cells. PLO is a member of the cholesterol-dependent cytolysin (CDC) family of which the primary structure only presents a low level of homology with other members from 31% to 45%. By deeply studying PLO, we can understand the overall pathogenic mechanism of CDC family proteins. This study established a mouse muscle tissue model infected with recombinant PLO (rPLO) and its single-point mutations, rPLO N139K and rPLO F240A, and explored its mechanism of causing inflammatory damage. The inflammatory injury abilities of rPLO N139K and rPLO F240A are significantly reduced compared to rPLO. This study elaborated on the inflammatory mechanism of PLO by examining its unit point mutations in detail. Our data also provide a theoretical basis and practical significance for future research on toxins and bacteria.

Trueperella pyogenes can cause various infections in the organs and tissues of different livestock (including pigs, cows, goats, and sheep), including mastitis, endometritis, pneumonia, or abscesses. Moreover, diseases induced by T. pyogenes cause significant economic losses in animal husbandry. In recent large-scale investigations, T. pyogenes has been identified as one of the main pathogens causing endometritis in lactating cows. However, the main treatment for the above-mentioned diseases is still currently antibiotic therapy. Understanding the impact of endometritis associated with T. pyogenes on the fertility of cows can help optimize antibiotic treatment for uterine diseases, thereby strategically concentrating the use of antimicrobials on the most severe cases. Therefore, it is particularly important to continuously monitor the prevalence of T. pyogenes and test its drug resistance. This study compared the uterine microbiota of healthy cows and endometritis cows in different cattle farms, investigated the prevalence of T. pyogenes, evaluated the genetic characteristics and population structure of isolated strains, and determined the virulence genes and drug resistance characteristics of T. pyogenes. An amount of 186 dairy cows were involved in this study and 23 T. pyogenes strains were isolated and identified from the uterine lavage fluid of dairy cows with or without endometritis.

Since it may be employed to guide the production of high-quality plant protein as a partial substitute for animal protein using sono-physico-chemical effects, it is important to investigate the mixing of animal and plant protein in ultrasound (UID)-assisted processing systems. A study group of sono-physico-chemical processing with five distinct soy protein isolate (SPI)/ sarcoplasmic protein (SPN) ratios was developed in this work. The results showed that adding additional SPN to the mixed protein can increase its sono-physico-chemical impact, and this effect is greatest when the ratio of SPI to SPN is 1:3. The high SPN group's grafting rate rose from 39.13% to 55.26% in comparison to the high SPI content group. Quercetin (Que) may more readily modify SPN than SPI in the “dual protein” system used in this work, highlighting the critical function of plant protein in controlling the effects of UID-assisted processing in the “dual protein” system. Changes in apparent viscosity and microstructure are the primary parameters that affect the severity of sono-physico-chemical effects in SPI/SPN mixed protein systems, in addition to structural variables.

Alfalfa (Medicago sativa) is a perennial forage legume that is widely distributed all over the world; therefore, it has an extremely complex genetic background. Though population structure and phylogenetic studies have been conducted on a large group of alfalfa nuclear genomes, information about the chloroplast genomes is still lacking. Chloroplast genomes are generally considered to be conservative and play an important role in population diversity analysis and species adaptation in plants. Here, 231 complete alfalfa chloroplast genomes were successfully assembled from 359 alfalfa resequencing data, on the basis of which the alfalfa chloroplast pan-genome was constructed. We investigated the genetic variations of the alfalfa chloroplast genome through comparative genomic, genetic diversity, phylogenetic, population genetic structure, and haplotype analysis. Meanwhile, the expression of alfalfa chloroplast genes under cold stress was explored through transcriptome analysis. As a result, chloroplast genomes of 231 alfalfa lack an IR region, and the size of the chloroplast genome ranges from 125,192 bp to 126,105 bp. Using population structure, haplotypes, and construction of a phylogenetic tree, it was found that alfalfa populations could be divided into four groups, and multiple highly variable regions were found in the alfalfa chloroplast genome. Transcriptome analysis showed that tRNA genes were significantly up-regulated in the cold-sensitive varieties, while rps7, rpl32, and ndhB were down-regulated, and the editing efficiency of ycf1, ycf2, and ndhF was decreased in the cold-tolerant varieties, which may be due to the fact that chloroplasts store nutrients through photosynthesis to resist cold. The huge number of genetic variants in this study provide powerful resources for molecular markers.

The newly prepared monolayer (ML) SiAs is expected to be a candidate channel material for next-generation nano-electronic devices in virtue of its proper bandgap, high carrier mobility, and anisotropic properties. The interfacial properties in ML SiAs field-effect transistors are comprehensively studied with electrodes (graphene, V2CO2, Au, Ag, and Cu) by using ab initio electronic structure calculations and quantum transport simulation. It is found that ML SiAs forms a weak van der Waals interaction with graphene and V2CO2, while it forms a strong interaction with bulk metals (Au, Ag, and Cu). Although ML SiAs has strong anisotropy, it is not reflected in the contact property. Based on the quantum transport simulation, ML SiAs forms n-type lateral Schottky contact with Au, Ag, and Cu electrodes with the Schottky barrier height (SBH) of 0.28 (0.27), 0.40 (0.47), and 0.45 (0.33) eV along the a (b) direction, respectively, while it forms p-type lateral Schottky contact with a graphene electrode with a SBH of 0.34 (0.28) eV. Fortunately, ML SiAs forms an ideal Ohmic contact with the V2CO2 electrode. This study not only gives a deep understanding of the interfacial properties of ML SiAs with electrodes but also provides a guide for the design of ML SiAs devices.

Narirutin, extracted from the dried ripe pericarp of Rutaceae orange and its cultivated varieties, is a dihydroflavone compound with various biological activities and pharmacological effects. So far as we know, the metabolism profiling of narirutin has been insufficient until now. In the present study, an efficient method was employed to perform rapid analysis and identification of narirutin metabolites by using ultra-high performance liquid chromatography quadrupole exactive orbitrap MS/MS (UHPLC-Q-Exactive Orbitrap MS/MS) combined with an analogous core recursion (ACR) analysis strategy. Firstly, according to the basic core structure of the dihydroflavonoid, the cleavage mode and fragmentation ions of narirutin were summarized. Secondly, based on the difference of the substituent groups, the fragment ions of narirutin were preliminarily inferred and verified by the secondary mass spectra of its standard compound. Thirdly, the fragment ions of narirutin in positive and negative ion modes were summarized to provide a basis for the identification of metabolites. Fourthly, candidate metabolites were accurately and tentatively identified according to the cleavage law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic fragment ion clusters (DFICs) and characteristic suggestive ions (CSIs) deduced preliminarily. Finally, a total of 46 metabolites (30 in vivo and 19 in vitro), including prototype drugs were identified based on the ACR analysis strategy, chromatographic retention behavior of metabolites, corresponding ClogP value and accurate molecular weight. Among them, 22 metabolites were discovered in rats plasma, 12 in urine, 4 in liver tissue, 19 in liver microsomes, respectively. Additionally, metabolites relative contents were also studied by extracted ion chromatography (EIC) method. Our result also illustrated that narirutin primarily underwent glucuronidation, sulfation, glutathione binding, deglycosylation, oxidation, reduction, methylation, hydroxylation, ring-opening and their composite reactions. A novel strategy was constructed to comprehensively elucidate the biotransformation pathways of narirutin in vitro and in vivo, and a systematic metabolic profile of narirutin was generated. This study provided a great reference for further understanding of the biotransformation pathways and guiding for clinical application of narirutin.

Background: Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav. (AD) is a tall perennial herb named Baizhi in Chinese Medical Works. Its medicinal use was first recorded in Shennong's Classic of Material Medical, the first herbal monograph in ancient China. Aim of the review: This review systematically summarises and evaluates traditional applications, botany, chemistry, and pharmacology of AD. This review aims to support the researchers who would like to explore its further potential as a medical agent. Materials and methods: The information was collected from Web of Science (https://www.webofscience.com), PubMed (https://pubmed.ncbi.nlm.nih.gov), CNKI (https://kns.cnki.net), Dissertations, Chinese Pharmacopoeia, and Government documents. The keyword used in the literature search was Angelica dahurica. The chemical structures of the compounds in AD were obtained from either research articles or PubChem. The historical origin and ethnopharmacology of AD were reviewed in detail. In addition, relevant information was obtained from regional and global unpublished sources. The plant's name and its classifications were confirmed using the Medicinal Plant Name Service (http://mpns.kew.org) and Plants of the World Online (https://powo.science.kew.org). Results: Over time, AD has been used extensively for its medicinal uses. The bioactive chemical compound present in it is imperatorin (IMP). It has anti-inflammatory, analgesic, and other therapeutic effects, and it is used as a marker for the quality evaluation of AD. The most studied part of the plant is the root. The root contains coumarins and volatile oil. Modern science has found that AD has the ability to treat skin wounds, analgesic, anti-inflammatory, anti-tumor, anti-depressant, and antioxidant effects, etc. Conclusions: This paper presents a detailed comparative analysis of available resources, confirming the origin, traditional applications, and therapeutic uses of AD. Most importantly, it is widely welcomed as a therapeutic drug. The results of several studies showed that the chemical components of AD were more deeply involved in the central nervous system and histopathological mechanisms. Moreover, AD not only has medical effects but also can be used as food condiments and food accessories.

This study investigated glass ceramics produced using coal gasification slag (CGS) and petrochemical incineration fly ash (PIFA) to immobilize hazardous heavy metals such as Cr and As. However, the crystallization kinetics and stabilization behavior mechanism of different heavy metals in the petrochemical incineration fly ash-derived glass-ceramics remains unclear. And X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and inductively coupled plasma mass spectrometry were used to characterize glass and crystalline products. In this paper, we reported the crystallization kinetics and chemical leaching characteristics of the glass ceramic. A low crystallization activation energy of 121.49 kJ/mol was achieved from crystallization peak of several different heating rates around 850°C, implying that it is easier to produce the glass ceramics at that temperature. The Avrami parameter of the former crystallization was determined to be 1.23 ± .12, which indicated two-dimensional crystal growth with heterogeneous nucleation. The toxicity characteristic leaching procedure results indicated that the heavy metals were well solidified, and that the leaching concentration was significantly lower than the limit specified by governmental agencies. The potentially toxic element index of the parent glass and the two glass ceramics were 11.7, 5.8, and 3.6, respectively. Therefore, the conversion of hazardous petrochemical incineration fly ash and other solid waste into environmentally friendly glass ceramics shows considerable potential and reliability.

Neomangiferin (NMF) is an extremely special xanthone that could be simultaneously attributed to C-glycoside and O-glycoside with a variety of biological activities, such as anti-inflammatory, antitumor, antipyretic, and so on. So far as we know, the metabolism profiling has been insufficient until now. Herein, Drug Metabolite Cluster Centers (DMCCs)-based Strategy has been developed to profile the NMF metabolites in vivo and in vitro. Firstly, the DMCCs was proposed depending on literature-related and preliminary analysis results. Secondly, the specific metabolic rule was implemented to screen the metabolites of candidate DMCCs from the acquired Ultra High Performance Liquid Chromatography Quadrupole Exactive Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap MS) data by extracted ion chromatography (EIC) method. Thirdly, candidate metabolites were accurately and tentatively identified according to the pyrolysis law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic product ions (DPIs) deduced preliminarily. Finally, network pharmacology was adopted to elucidate the anti-inflammatory action mechanism of NMF on the basis of DMCCs. As a result, 3 critical metabolites including NMF, Mangiferin (MF) and Norathyriol (NA) were proposed as DMCCs, and a total of 61 NMF metabolites (NMF included) were finally screened and characterized coupled with 3 different biological sample preparation methods including solid phase extraction (SPE), acetonitrile precipitation and methanol precipitation. Among them, 32 metabolites were discovered in rat urine, 30 in rat plasma, 12 in rat liver, 9 metabolites in liver microsomes and 8 in rat faeces, respectively. Our results also illustrated that NMF primarily underwent deglucosylation, glucuronidation, methylation, sulfation, dihydroxylation and their composite reactions in vivo and in vitro. Additionally, network pharmacology analysis based on DMCCs revealed 85 common targets of disease-metabolites, and the key targets were TNF, EGFR, ESR1, PTGS2, HIF1A, IL-2, PRKCA and PRKCB. They exerted anti-inflammatory effects mainly through the pathways of inflammatory response, calcium-dependent protein kinase C activity, nitrogen metabolism, pathways in cancer and so on. In general, our study constructed a novel strategy to comprehensive elucidate the biotransformation pathways of NMF in vivo and in vitro, and provided vital reference for further understanding its anti-inflammatory action mechanism. Moreover, the established strategy could be generalized to the metabolism and action mechanism study of other natural products.

Abstract In fuel cells, the generally low oxygen reduction reactions (ORR) rate at the cathode is a major factor limiting the overall performance of fuel cell, so the development of high‐performance, stable and inexpensive ORR electrocatalysts is a major researching direction. Nano‐electrocatalysts, especially one‐dimensional (1D) electrocatalysts, exhibit good catalytic behavior in fuel cell reactions due to their unique anisotropic structure, large specific surface area, high elasticity and excellent stability. To date, many advanced 1D electrocatalysts have been reported for optimizing the cathode ORR of fuel cells. Therefore, a comprehensive review of the structural design of 1D nano‐electrocatalysts and a systematic analysis of their enhanced performance still need further summarized and concluded. In this review, we firstly introduce the main synthetic methods of 1D electrocatalysts, and then discuss the recent advances and advantages of different structured 1D electrocatalysts involving nanofibers, nanotubes, nanorods, nanochains, nanowires, nanobelts, nanoneedles, nanowhiskers, and coaxial nanocables. In addition, we also introduce 1D electrocatalysts while highlighting advanced strategies and preparation methods for these different structured 1D electrocatalysts to improve ORR performance. Finally, we prospect the future development of 1D ORR electrocatalysts.

Summary: Utilization of naturally occurring resources to construct functional catalytic materials is significantly important, and facile and environmental-benign strategies are highly desired to afford the materials having a specific structure and good catalytic activity. Herein, we reported an innovative deep eutectic solvent (DES)-assisted strategy to synthesize zirconium phytate with a thin nanosheet structure (denoted as Zr-Phy-DES) using plant-originated phytic acid (PhyA) as the renewable building block. This strategy was eco-friendly and adjustable owing to the designability of DESs. The Zr-Phy-DES as an acidic catalyst showed high activity on two important biomass transformations, i.e., dehydration of carbohydrates and Meerwein-Ponndorf-Verley reduction of ethyl levulinate. Interestingly, Zr-Phy-DES showed higher catalytic performance than the zirconium phytates prepared in ethylene glycol and N,N-dimethylformamide, confirming the advantage of DESs for preparing functional materials. Notably, the unique feature of this proposed strategy is that renewable catalysts are prepared in an environmental-benign solvent for efficiently catalyzing biomass transformation.

Abstract Background To investigate the pharmacokinetics of 6-O-demethylmenisporphine, an oxoisoaporphine alkaloid with significant anti-tumor activities and isolated from Menispermi Rhizoma, a novel and sensitive HPLC assay was established for 6-O-demethylmenisporphine quantification in rat plasma. Methods Peak responses were detected by a highly selective and sensitive fluorescence detector with 426-nm excitation and 514-nm emission wavelengths. Curcumin was employed as the internal standard (IS). A Capcell Pak C18 column (150 mm × 4.6 mm i.d., 5 μm) and an isocratic elution procedure with a flow rate of 1.0 mL/min were used to exclude the endogenous interfering substance. Acetonitrile-water (68:32, v/v) containing 1% formic acid was employed as mobile phase. A 7-point calibration curve that covered the concentration range of 10–2500 ng/mL was constructed. Results A good linearity was observed with a correlation coefficient (r) of 0.9993. The lower limit of quantification for 6-O-demethylmenisporphine was 10 ng/mL. The mean recoveries of analyte in rat plasma exceeded 80.5%. The precision at four concentration levels was within 11.3% and the accuracy ranged from − 7.6 to 6.7%. Conclusion Using this new HPLC-FLD method, the investigation of plasma samples from rats following oral dosing of neat compound and Menispermi Rhizoma extract was successfully conducted. The results will provide a reference for the evaluation of preclinical safety of 6-O-demethylmenisporphine.

The technique of pig cloning holds great promise for the livestock industry, life science, and biomedicine. However, the prenatal death rate of cloned pig embryos is extremely high, resulting in a very low cloning efficiency. This limits the development and application of pig cloning. In this study, we utilized embryo biopsy combined with microproteomics to identify potential factors causing the developmental arrest in cloned pig embryos. We verified the roles of two potential regulators, PDCD6 and PLK1, in cloned pig embryo development. We found that siRNA-mediated knockdown of PDCD6 reduced mRNA and protein expression levels of the pro-apoptotic gene, CASP3, in cloned pig embryos. PDCD6 knockdown also increased the cleavage rate and blastocyst rate of cloned porcine embryos. Overexpression of PLK1 via mRNA microinjection also improved the cleavage rate of cloned pig embryos. This study provided a new strategy to identify key factors responsible for the developmental defects in cloned pig embryos. It also helped establish new methods to improve pig cloning efficiency, specifically by correcting the expression pattern of PDCD6 and PLK1 in cloned pig embryos.

Root-zone CO2 is a major factor that affects crop growth, development, nutrient uptake, and metabolism. Oriental melon is affected by root-zone gases during growth, the microstructure, sugar and starch contents, enzymatic activities related to sugar and starch metabolism, and gene expression in the roots of oriental melon seedlings were investigated under three root-zone CO2 concentrations (CK: 0.2%, T1: 0.4%, T2: 1.1%). Elevated root-zone CO2 altered the cellular microstructure, accelerated the accumulation and release of starch grains, disrupted organelle formation, and accelerated root senescence. The sugar and starch contents and metabolic activity in the roots increased within a short duration following treatment. Compared to the control, 232 and 1492 differentially expressed genes (DEGs) were identified on the 6th day of treatment in T1 and T2 plants, respectively. The DEGs were enriched in three metabolic pathways. The majority of genes related to sucrose and starch hydrolysis were upregulated, while the genes related to sucrose metabolism were downregulated. The study revealed that oriental melon seedlings adapt to elevated root-zone CO2 stress by adjusting sugar and starch metabolism at the transcriptome level and provides new insights into the molecular mechanism underlying the response to elevated root-zone CO2 stress.

Weed interference in the crop field is one of the major biotic stresses causing dramatic crop yield losses, and the development of herbicide-resistant crops is critical for weed control in the application of herbicide technologies. To identify herbicide-resistant germplasms, we screened 854 maize inbreed lines and 25,620 seedlings by spraying them with 1 g/L glufosinate. One plant (L336R), possibly derived from a natural variation of line L336, was identified to have the potential for glufosinate tolerance. Genetic analysis validated that the glufosinate tolerance of L336R is conferred by a single locus, which was tentatively designated as ZmGHT1. By constructing a bi-parental population derived from L336R, and a glufosinate sensitive line L312, ZmGHT1 was mapped between molecular markers M9 and M10. Interestingly, genomic comparation between the two sequenced reference genomes showed that large scale structural variations (SVs) occurred within the mapped region, resulting in 2.16 Mb in the inbreed line B73, and 11.5 kb in CML277, respectively. During the fine mapping process, we did not detect any additional recombinant, even by using more than 9500 F2 and F3 plants, suspecting that SVs should also have occurred between L336R and L312 in this region, which inhibited recombination. By evaluating the expression of the genes within the mapped interval and using functional annotation, we predict that the gene Zm00001eb361930, encoding an aminotransferase, is the most likely causative gene. After glufosinate treatment, lower levels of ammonia content and a higher activity of glutamine synthetase (GS) in L336R were detected compared with those of L336 and L312, suggesting that the target gene may participate in ammonia elimination involving GS activity. Collectively, our study can provide a material resource for maize herbicide resistant breeding, with the potential to reveal a new mechanism for herbicide resistance.

Bovine mastitis seriously affects bovine health and dairy product quality. Escherichia coli is the most important pathogen in the environment and dairy products. Enteropathogenic Escherichia coli (EPEC) is a zoonotic pathogen, which seriously threatens the health of people and dairy cows. We recently reported that E. coli can induce endogenous apoptosis in bovine mammary epithelial cells. However, the mechanism of EPEC-damaged mitochondria and -induced bovine mastitis is unclear. In this study, we found that EPEC can induce DRP-1-dependent mitochondrial fission and apoptosis. This was verified by the application of Mdivi, a DRP-1 inhibitor. Meanwhile, in order to verify the role of the Map virulence factor in EPEC-induced bovine mastitis, we constructed a map mutant, complementary strain, and recombinant plasmid MapHis. In the present study, we find that Map induced DRP-1-mediated mitochondrial fission, resulting in mitochondrial dysfunction and apoptosis. These inferences were further verified in vivo by establishing a mouse mastitis model. After the map gene was knocked out, breast inflammation and apoptosis in mice were significantly alleviated. All results show that EPEC targets mitochondria by secreting the Map virulence factor to induce DRP-1-mediated mitochondrial fission, mitochondrial dysfunction, and endogenous apoptosis in bovine mastitis.

Hydrogenated crystalized TiO2−x with oxygen vacant (OV) doping has attracted considerable attraction, owing to its impressive photoactivity. However, amorphous TiO2, as a common allotrope of titania, is ignored as a hydrogenated templet. In this work, hydrogenated amorphous TiO2−x (HAm-TiO2−x) with engineered surface OV and high surface area (176.7 cm2 g−1) was first prepared using a unique liquid plasma hydrogenation strategy. In HAm-TiO2−x, we found that OV was energetically retained in the subsurface region; in particular, the subsurface OV-induced energy level preferred to remain under the conduction band (0.5 eV) to form a conduction band tail and deep trap states, resulting in a narrow bandgap (2.36 eV). With the benefits of abundant light absorption and efficient photocarrier transportation, HAm-TiO2−x coated glass has demonstrated superior visible-light-driven self-cleaning performances. To investigate its formaldehyde photodegradation under harsh indoor conditions, HAm-TiO2−x was used to decompose low-concentration formaldehyde (~0.6 ppm) with weak-visible light (λ = 600 nm, power density = 0.136 mW/cm2). Thus, HAm-TiO2−x achieved high quantum efficiency of 3 × 10−6 molecules/photon and photoactivity of 92.6%. The adsorption capabilities of O2 (−1.42 eV) and HCHO (−1.58 eV) in HAm-TiO2−x are both largely promoted in the presence of subsurface OV. The surface reaction pathway and formaldehyde decomposition mechanism over HAm-TiO2−x were finally clarified. This work opened a promising way to fabricate hydrogenated amorphous photocatalysts, which could contribute to visible-light-driven photocatalytic environmental applications.

Summary: Feedback circuits are one of the major causes underlying tumor resistance. Thus, compounds that target one oncogenic pathway with simultaneously blocking its compensatory pathway will be of great value for cancer treatment. Here, we develop a new MEK inhibitor designated as KZ-02 that exhibits unexpectedly higher cytotoxicity than its starting compound AZD6244, a well-known MEK inhibitor, in colorectal cancer (CRC). Subsequent kinase selectivity study identified Pim-1 as an additional cellular target for KZ-02. Further studies showed that AZD6244 and Pim-1 1 (a Pim-1 inhibitor) have a synergistic effect on CRC suppression. Mechanistic study revealed that MEK inhibition by AZD6244 leads to increased Pim-1 expression, which could be a general mechanism behind the compromised cell-killing activity of MEK inhibitors. KZ-02, despite increasing Pim-1 mRNA expression, simultaneously promotes Pim-1 proteasomal degradation. Therefore, we uncover a new MEK inhibitor KZ-02 with significantly enhanced antitumor activity by co-targeting MEK and Pim-1.

In this study, a series of novel 1,5-di(nitramino)tetrazole (DNAT)-based bimetallic energetic coordination polymers, MK2(DNAT)2·4H2O [M = Fe, Cu, Ni, Co, and Zn], were designed and synthesized in a simple and convenient self-assembly synthetic process. The obtained compounds were fully characterized by IR spectroscopy, multinuclear NMR spectroscopy, elemental analysis, and differential scanning calorimetry (DSC). Additionally, the structures of target compounds were confirmed by single-crystal X-ray diffraction. Based on the room-temperature X-ray densities (2.095–2.138 g cm−3) and the calculated (CBS–QB3) heats of formation (−41.3 to 170.5 kJ mol−1), the detonation properties such as detonation velocities (8,147.0–8,478.4 m s−1) and detonation pressures (29.7–32.8 GPa) were computed using the EXPLO5 v6.04 program. Their excellent energetic properties indicated that they could serve as promising “green” primary explosives for replacement of lead azide (LA).

Due to powerful data representation ability, deep learning has dramatically improved the state-of-the-art in many practical applications. However, the utility highly depends on fine-tuning of hyper-parameters, including learning rate, batch size, and network initialization. Although many first-order adaptive methods (e.g., Adam, Adagrad) have been proposed to adjust learning rate based on gradients, they are susceptible to the initial learning rate and network architecture. Therefore, the main challenge of using deep learning in practice is how to reduce the cost of tuning hyper-parameters. To address this, we propose a heuristic zeroth-order learning rate method, Adacomp, which adaptively adjusts the learning rate based only on values of the loss function. The main idea is that Adacomp penalizes large learning rates to ensure the convergence and compensates small learning rates to accelerate the training process. Therefore, Adacomp is robust to the initial learning rate. Extensive experiments, including comparison to six typically adaptive methods (Momentum, Adagrad, RMSprop, Adadelta, Adam, and Adamax) on several benchmark datasets for image classification tasks (MNIST, KMNIST, Fashion-MNIST, CIFAR-10, and CIFAR-100), were conducted. Experimental results show that Adacomp is not only robust to the initial learning rate but also to the network architecture, network initialization, and batch size.

Grasslands play an irreplaceable role in maintaining carbon balance and stabilizing the entire Earth’s ecosystem. Although the grasslands in Inner Mongolia are sensitive and vulnerable to climate change, a generalized effect of climate change on the grasslands is still unavailable. In this study, we analyzed the effects of annual mean precipitation and annual mean temperature on the normalized difference vegetation index from 1982 to 2010 on the Inner Mongolia Plateau. Our results indicated that the normalized difference vegetation index was mostly affected by precipitation, followed by temperature. Spatially, temperature and precipitation had greater effects on normalized difference vegetation index in dry regions than in wet ones. In time series, the effect of precipitation on normalized difference vegetation index had significantly decreased from 1982 to 2010 (R2 = 0.11, p > 0.05). However, the effect of temperature on normalized difference vegetation index remained stable. The high variation effect of precipitation on normalized difference vegetation index was due to the significant decrease in precipitation from 1980 to 2010. Thus, 35.47% and 0.56% of the dynamic of normalized difference vegetation index from 1982 to 2010 was accounted for by the precipitation and temperature, respectively. Our findings highlighted that grasslands are adaptable to the significant increase in temperature, but are sensitive to the decrease in precipitation on the Inner Mongolia Plateau.

Partial Discharge (PD) measurements of large generators are extremely affected and hampered by noise, making the denoising of PD signal an inevitable issue. Wavelet shrinkage is the most commonly employed method for PD signal denoising. The appropriate mother wavelet and decomposition level are critically important for the denoising performance. In consideration of the PD signal characteristics of large generators, a novel wavelet shrinkage scheme for PD signal denoising is presented. In the scheme, a scale dependent wavelet selection method is proposed; the core idea is that the optimum wavelet at each scale is selected as the one maximizing the energy ratio of coefficients beside and inside the range formed by the threshold, which correspond to the signal to be reserved and noise to be removed, respectively. In addition, taking into account the influence of mother wavelet at each scale on the decomposition level, an approach for decomposition level determination is put forward based on the energy composition after decomposition at each scale. The application results on the simulated signals with different SNR obtained by combining the various pulses and measured signal on-site show the effectiveness of the proposed scheme. Besides, the denoising results are compared with that of the existing wavelet selection methods and the proposed wavelet selection method shows an obvious advantage.