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ABSTRACT Rapid and clean drying of round bamboo is a highly desired process in utilizing bamboo resources. The properties of dried round bamboo (Phyllostachys iridescens C.Y.Yao & S.Y. Chen), such [...]

Quantum sealed-bid auction (QSA) is expected to provide an alternative to classical sealed-bid auction to defend against attacks from quantum adversaries. However, most previous QSA protocols required bidders to have quantum operation capabilities, resulting in excessive quantum resource requirements. To relieve the burden of protocol quantum resources, a measurement-based quantum sealed-bid auction protocol with the one-way transmission is proposed. Compared to previous protocols, our protocol only requires bidders to perform measurements, and no other operations, such as Pauli or Phase operations, are required. In order to verify the correctness and feasibility of the proposed QSA protocol, the corresponding quantum circuits are designed and simulated by IBM Qiskit. The proposed protocol satisfies security properties, including anonymity, fairness, verifiability, privacy, and non-repudiation. In addition, we further extend the protocol to scenarios that do not require an auctioneer and achieve bid privacy protection for unsuccessful bidders. Therefore, our protocol may have broad applications in auction scenarios.

Pathogen isolation and identification were performed on Actinidia arguta‘Longcheng No. 2’ occurring bacterial canker from Liaoning Province, China. The pathogenic bacteria were identified as Pseudomonas syringaepv. actinidiae(Psa) by the analysis of morphology,16S rRNA and gyrBsequence, which were identified as Psa biovar 2 by Psa-specific primer sequence analysis. The pathogenicity tests were carried out with the isolate ‘R12’ and type strain ‘M228’ (biovar 3) as a control; the results showed that the phloem of green stems in A. arguta‘Kuilv’ could be infect rapidly by R12, and milky mucus flowed from wounds, then the phloem turned black-brown, but it had strong resistance to Psa M228. In order to evaluate the resistance on Psa R12, 54 A. argutagermplasm resources were infected by artificial inoculation of stems, with A. deliciosacv. ‘Hongyang’ and A. chinensiscv. ‘Xuxiang’, as control plant material, and their resistance levels were classified according to the disease index. The 54 tested materials exhibited differences in resistance to Psa R12, but no immune materials were found. In general, the germplasms were divided into five disease resistance categories, including 2 accessions with high resistance ‘Jianfengkuilv’ and ‘TL20013’, accounted for 3.70% of all the inoculated accessions; there were 11 resistant accessions, 15 tolerant accessions, 21 susceptible accessions, 5 highly susceptible accessions among them, accounted for 20.37%, 27.78%, 38.89% and 9.26%, respectively. In this study, the screening of disease-resistant germplasms could lay a foundation for further research on gene mapping, resistance mechanisms and breeding-resistant varieties of A. argutato Psa.

Dimethylsulfide (DMS) is the major biosulfur source emitted to the atmosphere with key roles in global sulfur cycling and potentially climate regulation. The main precursor of DMS is thought to be dimethylsulfoniopropionate. However, hydrogen sulfide (H2S), a widely distributed and abundant volatile in natural environments, can be methylated to DMS. The microorganisms and the enzymes that convert H2S to DMS, and their importance in global sulfur cycling were unknown. Here we demonstrate that the bacterial MddA enzyme, previously known as a methanethiol S-methyltransferase, could methylate inorganic H2S to DMS. We determine key residues involved in MddA catalysis and propose the mechanism for H2S S-methylation. These results enabled subsequent identification of functional MddA enzymes in abundant haloarchaea and a diverse range of algae, thus expanding the significance of MddA mediated H2S methylation to other domains of life. Furthermore, we provide evidence for H2S S-methylation being a detoxification strategy in microorganisms. The mddAgene was abundant in diverse environments including marine sediments, lake sediments, hydrothermal vents and soils. Thus, the significance of MddA-driven methylation of inorganic H2S to global DMS production and sulfur cycling has likely been considerably underestimated.

Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease. Keratinocyte dysfunction plays a central role in AD development. MicroRNA is a novel player in many inflammatory and immune skin diseases. In this study, we investigated the potential function and regulatory mechanism of miR‐193b in AD. Inflamed human keratinocytes (HaCaT) were established by tumor necrosis factor (TNF)‐α/interferon (IFN)‐γ stimulation. Cell viability was measured using MTT assay, while the cell cycle was analyzed using flow cytometry. The cytokine levels were examined by enzyme‐linked immunosorbent assay. The interaction between Sp1, miR‐193b, and HMGB1 was analyzed using dual luciferase reporter and/or chromatin immunoprecipitation (ChIP) assays. Our results revealed that miR‐193b upregulation enhanced the proliferation of TNF‐α/IFN‐γ‐treated keratinocytes and repressed inflammatory injury. miR‐193b negatively regulated high mobility group box 1 (HMGB1) expression by directly targeting HMGB1. Furthermore, HMGB1 knockdown promoted keratinocyte proliferation and inhibited inflammatory injury by repressing nuclear factor kappa‐B (NF‐κB) activation. During AD progression, HMGB1 overexpression abrogated increase of keratinocyte proliferation and repression of inflammatory injury caused by miR‐193b overexpression. Moreover, transcription factor Sp1 was identified as the biological partner of the miR‐193b promoter in promoting miR‐193b expression. Therefore, Sp1 upregulation promotes keratinocyte proliferation and represses inflammatory injury during AD development via promoting miR‐193b expression and repressing HMGB1/NF‐κB activation.

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur compound in marine environments with important functions in both microorganisms and global biogeochemical carbon and sulfur cycling. The SAR11 clade and marine Roseobactergroup (MRG) represent two major groups of heterotrophic bacteria in Earth’s surface oceans, which can accumulate DMSP to high millimolar intracellular concentrations. However, few studies have investigated how SAR11 and MRG bacteria import DMSP. Here, through comparative genomics analyses, genetic manipulations, and biochemical analyses, we identified an ABC (ATP-binding cassette)-type DMSP-specific transporter, DmpXWV, in Ruegeria pomeroyiDSS-3, a model strain of the MRG. Mutagenesis suggested that DmpXWV is a key transporter responsible for DMSP uptake in strain DSS-3. DmpX, the substrate binding protein of DmpXWV, had high specificity and binding affinity towards DMSP. Furthermore, the DmpX DMSP-binding mechanism was elucidated from structural analysis. DmpX proteins are prevalent in the numerous cosmopolitan marine bacteria outside the SAR11 clade and the MRG, and dmpXtranscription was consistently high across Earth’s entire global ocean. Therefore, DmpXWV likely enables pelagic marine bacteria to efficiently import DMSP from seawater. This study offers a new understanding of DMSP transport into marine bacteria and provides novel insights into the environmental adaption of marine bacteria.

D-glutamate (D-Glu) is an essential component of bacterial peptidoglycans, representing an important, yet overlooked, pool of organic matter in global oceans. However, little is known on D-Glu catabolism by marine microorganisms. Here, a novel catabolic pathway for D-Glu was identified using the marine bacterium Pseudoalteromonassp. CF6-2 as the model. Two novel enzymes (DgcN, DgcA), together with a transcriptional regulator DgcR, are crucial for D-Glu catabolism in strain CF6-2. Genetic and biochemical data confirm that DgcN is a N-acetyltransferase which catalyzes the formation of N-acetyl-D-Glu from D-Glu. DgcA is a racemase that converts N-acetyl-D-Glu to N-acetyl-L-Glu, which is further hydrolyzed to L-Glu. DgcR positively regulates the transcription of dgcNand dgcA. Structural and biochemical analyses suggested that DgcN and its homologs, which use D-Glu as the acyl receptor, represent a new group of the general control non-repressible 5 (GCN5)-related N-acetyltransferases (GNAT) superfamily. DgcA and DgcN occur widely in marine bacteria (particularly Rhodobacterales) and halophilic archaea (Halobacteria) and are abundant in marine and hypersaline metagenome datasets. Thus, this study reveals a novel D-Glu catabolic pathway in ecologically important marine bacteria and halophilic archaea and helps better understand the catabolism and recycling of D-Glu in these ecosystems.

In the past few years, the emergence of pre-training models has brought uni-modal fields such as computer vision (CV) and natural language processing (NLP) to a new era. Substantial works have shown that they are beneficial for downstream uni-modal tasks and avoid training a new model from scratch. So can such pre-trained models be applied to multi-modal tasks? Researchers have explored this problem and made significant progress. This paper surveys recent advances and new frontiers in vision-language pre-training (VLP), including image-text and video-text pre-training. To give readers a better overall grasp of VLP, we first review its recent advances in five aspects: feature extraction, model architecture, pre-training objectives, pre-training datasets, and downstream tasks. Then, we summarize the specific VLP models in detail. Finally, we discuss the new frontiers in VLP. To the best of our knowledge, this is the first survey focused on VLP. We hope that this survey can shed light on future research in the VLP field.

Collagen oligopeptides have wide applications in foods, pharmaceuticals, cosmetics, and others due to their high bioactivities and bioavailability. The S8 family is the second-largest family of serine proteases. Several collagenolytic proteases from this family have been reported to have good potential in the preparation of collagen oligopeptides, however, the underlying mechanism remains unknown. A4095 was the most abundant S8 protease secreted by the protease-producing bacterium Anoxybacillus caldiproteolyticus1A02591. Here, we characterized A4095 as an S8 collagenolytic protease and illustrated its structural basis to produce collagen oligopeptides. Protease A4095 preferentially hydrolyzed the Y-Gly peptide bonds in denatured bovine bone collagen, leading to high production (62.48% <1000 Da) of collagen oligopeptides. Structural and mutational analyses indicated that A4095 has a unique S1′ substrate-binding pocket to preferentially bind Gly, which is the structural determinant for the high production of collagen oligopeptides. This study provides mechanistic insight into the advantage of the S8 collagenolytic proteases in preparing collagen oligopeptides.

The MADS-box (DAM) gene PpDAM6, which is related to dormancy, plays a key role in bud endodormancy release, and the expression of PpDAM6decreases during endodormancy release. However, the interaction network that governs its regulation of the endodormancy release of flower buds in peach remains unclear. In this study, we used yeast two-hybrid (Y2H) assays to identify a mitogen-activated protein kinase, PpMAPK6, that interacts with PpDAM6in a peach dormancy-associated SSHcDNA library. PpMAPK6is primarily located in the nucleus, and Y2H and bimolecular fluorescence complementation (BiFC) assays verified that PpMAPK6interacts with PpDAM6by binding to the MADS-box domain of PpDAM6. Quantitative real-time PCR (qRT-PCR) analysis showed that the expression of PpMAPK6was opposite that of PpDAM6in the endodormancy release of three cultivars with different chilling requirements (Prunus persica‘Chunjie’, Prunus persicavar. nectarina ‘Zhongyou 5’, Prunus persica‘Qingzhou peach’). In addition, abscisic acid (ABA) inhibited the expression of PpMAPK6and promoted the expression of PpDAM6in flower buds. The results indicated that PpMAPK6might phosphorylate PpDAM6to accelerate its degradation by interacting with PpDAM6. The expression of PpMAPK6increased with decreasing ABA content during endodormancy release in peach flower buds, which in turn decreased the expression of PpDAM6and promoted endodormancy release.

Objective: The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism. Methods: A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group. Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters (oxygen partial pressure about 6.9 kPa) for 7 days. PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days. Pathological changes of the rat renal tissues were observed under a light microscope; the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cell-free DNA (cf-DNA) and reactive oxygen species (ROS) were measured; the expression levels of myeloperoxidase (MPO), citrullinated histone H3 (cit-H3), B-cell lymphoma 2 (Bcl-2), Bax, nuclear factor kappa B (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in rat renal tissues were detected by qRT-qPCR and Western blotting; the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining. Results: After hypoxia, the expression of NF-κB protein in renal tissues was significantly increased, the levels of SCr, BUN, cf-DNA and ROS in serum were significantly increased, the formation of NETs in renal tissues was significantly increased, and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues. When PDTC was used to inhibit NF-κB activation, NETs formation in renal tissue was significantly decreased, the expression level of Bcl-2 in renal tissues was significantly increased, the expression level of Bax was significantly decreased, and renal injury was significantly alleviated. Conclusion: HH induces the formation of NETs through the NF-κB signaling pathway, and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.

The amine submetabolome, including amino acids (AAs) and biogenic amines (BAs), is a class of small molecular compounds exhibiting important physiological activities. Here, a new pyrylium salt named 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate ([d0]-DMMIC) with stable isotope-labeled reagents ([d3]-/[d6]-DMMIC) was designed and synthesized for amino compounds. [d0]-/[d3]-/[d6]-DMMIC-derivatized had a charged tag and formed a set of molecular ions with an increase of 3.02 m/zand the characteristic fragment ions of m/z204.1:207.1:210.1. When DMMIC coupled with liquid chromatography-mass spectrometry (LC-MS), a systematic methodology evaluation for quantitation proved to have good linearity (R2between 0.9904 and 0.9998), precision (interday: 2.2–21.9%; intraday: 1.0–19.7%), and accuracy (recovery: 71.8–108.8%) through the test AAs. Finally, the methods based on DMMIC and LC-MS demonstrated the advantaged application by the nontargeted screening of BAs in a common medicinal herb Senecio scandensand an analysis of metabolic differences among the amine submetabolomes between the carcinoma and paracarcinoma tissues of esophageal squamous cell carcinoma (ESCC). A total of 20 BA candidates were discovered in S. scandensas well as the finding of 13 amine metabolites might be the highest-potential differential metabolites in ESCC. The results showed the ability of DMMIC coupled with LC-MS to analyze the amine submetabolome in herbs and clinical tissues.

Along with applying blockchain technology in the health care service system (HSS), many distributed solutions have been proposed to solve the centralized, data island problems. Although blockchain-enabled HSS has significantly changed the traditional management mode of medical Big Data [e.g., electronic medical records (EMRs)], some new problems such as ledger corpulence, data searchable security, and quantum attack threat are exposed. In this article, we first introduce an efficient EMRs management model called on-chain ledger and off-chain storage (OLOS), in which the indexes of EMRs are uploaded on public blockchain and the real EMRs data are stored in native server. This model can relieve the public ledger and save the public cloud space. Meanwhile, it can protect data security by keeping off the direct operation on real EMRs data. Then, to protect the cross-institutional EMRs sharing security and improve the quantum-resist ability, we proposed a secure keyword-searchable attribute-based encryption (KS-ABE) scheme based on lattice cryptography. Moreover, the scheme can prove to be secure against adaptive chosen-keyword attack and adaptive chosen-policy attack in the random oracle model. Besides, comparison analysis and experimental results show that our KS-ABE scheme has fewer communication costs and smaller key sizes than similar literary works.

To strengthen the face-centered-cubic (FCC) type CoCrFeNi high-entropy alloy (HEA) by in-situ reinforced phase, (CoCrFeNi)100−x(NbB2)x(x=0, 2, 4, 6, 8, at.%) alloys were prepared. Phase constitution, microstructure, tensile mechanical properties of the alloys were studied, and the mechanisms were discussed. Results show that the microstructure of all the reinforced alloys consists of the matrix FCC phase, Laves phase, and (Cr3Fe)Bxphase. The eutectic structure and (Cr3Fe)Bxphases are formed in the interdendritic region, and the eutectic structure is composed of Laves and FCC phases. When xincreases from 0 to 8, i.e., with increase of Nb and B elements, the volume fraction of Laves and (Cr3Fe)Bxphases increases gradually from 0 to 5.84% and 8.3%, respectively. Tensile testing results show that the ultimate strength of the alloys increases gradually from 409 MPa to 658 MPa, while the fracture strain decreases from 75% to 1.6%. Fracture analysis shows that the crack originates from the (Cr3Fe)Bxphase. The CoCrFeNi alloys are mainly strengthened by the second phase (Laves phase and boride phase).

Insect general odorant-binding proteins (GOBPs) play irreplaceable roles in filtering, binding, and transporting host odorants to olfactory receptors. Grapholita funebrana(Treitscheke) (Lepidoptera: Tortricidae), an economically important pest of fruit crops, uses fruit volatiles as cues to locate host plants. However, the functions of GOBPs in G. funebranaare still unknown. Three GOBP genes, namely, GfunGOBP1, GfunGOBP2, and GfunGOBP3, were cloned, and their expression profiles in different tissues were detected by the method of real-time quantitative PCR (RT-qPCR). The binding properties of recombinant GfunGOBPs (rGfunGOBPs) to various ligands were investigated via fluorescence binding assays. The three GfunGOBPswere mainly expressed in the antennae of both male and female moths. All these three rGfunGOBPs could bind to sex pheromones, while having varying affinities toward these pheromones. The three rGfunGOBPs also displayed a wide range of ligand-binding spectrums with tested host odorants. The rGfunGOBP1, rGfunGOBP2, and rGfunGOBP3 bound to 34, 33, and 30 out of the 41 tested odorants, respectively. Three rGfunGOBPs had overlapping binding activities to β-myrcene, (-)-α-phellandrene, and ethyl isovalerate with the Kiless than 3.0 μM. The rGfunGOBP1 and rGfunGOBP3 could selectively bind to several insecticides, whereas rGfunGOBP2 could not. Three rGfunGOBPs had the dual functions of selectively binding to sex pheromones and host odorants. Moreover, the rGfunGOBP1 and rGfunGOBP3 can also serve as ‘signal proteins’ and bind to different insecticides. This study contributed to elucidating the potential molecular mechanism of the olfaction for G. funebrana, and thereby promotes the development of effective botanical attractants or pheromone synergists to control G. funebrana.

During spermiogenesis, the formation of the mitochondrial sheath is critical for male fertility. The molecular processes that govern the development of the mitochondrial sheath remain unknown. Whether TBC1D21 serves as a GTPase-activating protein (GAP) for GTP hydrolysis in the testis is unclear, despite recent findings indicating that it collaborates with numerous proteins to regulate the formation of the mitochondrial sheath. To thoroughly examine the property of TBC1D21 in spermiogenesis, we applied the CRISPR/Cas9 technology to generate the Tbc1d21−/−mice, Tbc1d21D125A R128Kmice with mutation in the GAP catalytic residues (IxxDxxR), and Tbc1d21-3xFlagmice. Male Tbc1d21−/−mice were infertile due to the curved spermatozoa flagella. In vitro fertilization is ineffective for Tbc1d21−/−sperm, although healthy offspring were obtained by intracytoplasmic sperm injection. Electron microscopy revealed aberrant ultrastructural changes in the mitochondrial sheath. Thirty-four Rab vectors were constructed followed by co-immunoprecipitation, which identified RAB13 as a novel TBC1D21 binding protein. Interestingly, infertility was not observed in Tbc1d21D125A R128Kmice harboring the catalytic residue, suggesting that TBC1D21 is not a typical GAP for Rab-GTP hydrolysis. Moreover, TBC1D21 was expressed in the sperm mitochondrial sheath in Tbc1d21-3xFlagmice. Immunoprecipitation-mass spectrometry demonstrated the interactions of TBC1D21 with ACTB, TPM3, SPATA19, and VDAC3 to regulate the architecture of the sperm midpiece. The collective findings suggest that TBC1D21 is a scaffold protein required for the organization and stabilization of the mitochondrial sheath morphology.The formation of the mitochondrial sheath is critical for male fertility, but the molecular processes that govern the development of the mitochondrial sheath remain unknown. By using multiple transgenic mouse models, we demonstrated that TBC1D21 is an essential protein for sperm mitochondrial sheath assembly and male fertility. The Tbc1d21-/-mice were infertile due to the malformation of the mitochondrial sheath assembly. Importantly, Tbc1d21D125A R128Kmice were fertile, suggesting that TBC1D21 may not be a classic Rab-GTP hydrolysis protein. Tbc1d21-3XFlagmice elucidated that TBC1D21, ACTB, and TPM3 complex in the form of a double helix around the mitochondrial sheath to maintain its assembly structure. This research sheds light on the pivotal role of TBC1D21 in the organization and stabilization of the mitochondrial sheath morphology.Graphical Abstract

An intramolecular Cu-catalyzed asymmetric propargylic [4 + 2] cycloaddition of bis-N-nucleophile-functionalized propargylic esters has been realized in the support of a chiral tridentate N-ligand, (S,S)-Pybox-diOAc, leading to chiral tetrahydroisoindolo[2,1-a]quinoxalines in high yields and with good to excellent enantioselectivities. The reaction features high efficiency, simplicity, and broad substrate scope, thus providing a powerful and concise strategy for stereoselective access to optically active polycyclic heterocycle frameworks that are otherwise difficult to synthesize.

Based on the comprehensive study of geology and geophysics in African continent, three types of lithosphere (craton-type, orogenic-type and rift-type) can be identified. Considering lithosphere discontinuities as the boundary, two first-order tectonic units (mainly cratonic-type in the west and rift-type in the east) are proposed. Different types of lithosphere can be divided into secondary-order and third-order structural units, and the blocks within lithosphere can be further divided into fourth-order structural units. The geological history, the formation process and significance of different types of lithosphere in African continent are briefly discussed.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cose.2004.08.009 Byline: Xiu-Zhen Chen (a), Qing-Hua Zheng (a), Xiao-Hong Guan (a)(b), Chen-Guang Lin (a), Jie Sun (a) Abstract: How to evaluate network security threat quantitatively is one of key issues in the field of network security, which is vital for administrators to make decision on the security of computer networks. A novel model of security threat evaluation with a series of quantitative indices is proposed on the analysis of prevalent network intrusions. This model is based on multiple behavior information fusion and two indices of privilege validity and service availability that are proposed to evaluate the impact of prevalent network intrusions on system security, so as to provide security evolution over time, i.e., monitor security changes with respect to modification of security factors. The Markov model and the algorithm of D-S evidence reasoning are proposed to measure these two indices, respectively. Compared with other methods, this method mitigates the impact of unsuccessful intrusions on threat evaluation. It evaluates the impact of important intrusions on system security comprehensively and helps administrators to insight into intrusion steps, determine security state and identify dangerous intrusion traces. Testing in a real network environment shows that this method is reasonable and feasible in alleviating the tremendous task of data analysis and facilitating the understanding of the security evolution of the system for its administrators. Author Affiliation: (a) Center for Networked Systems and Information Security (CNSIS) and SKLMS Lab, Xi'an Jiaotong University, Xian 710049, China (b) Center for Intelligent and Networked Systems, Tsinghua University, Beijing 100084, China Article Note: (footnote) [star] The research presented in this paper is supported in part by the National Outstanding Young Investigator Grant (6970025), National Natural Science Foundation (60243001) and 863 High Tech Plan (2001AA140213) of China.

The experiment focused on the study aimed to investigate the effects of adding alanyl-glutamine (Ala-Gln) to the feed on the growth, serum biochemical parameters, and the mRNA expression levels of stress-related genes in largemouth bass (Micropterus salmoides) under dual stress conditions of density and flow rate. The fish were divided into three groups: control group, dual stress group and dual stress with 0.9 % Ala-Gln addition group, and underwent a 60 day aquaculture experiment. The data showed that final weight, average weight gain rate, specific growth rate and feed efficiency of largemouth bass significantly decreased under dual stress (P < 0.05). At the same time, the levels of glucose and malondialdehyde (MAD), the activities of aspartate aminotransferase (AST) and alanine transaminase (ALT) in serum increased significantly under dual stress, while the total antioxidant capacity and serum lysozyme activity decreased significantly (P < 0.05). Moreover, the mRNA expression of growth hormone (GH), insulin-like growth factor-Ⅰ(IGF-I), nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), nuclear transcription factor E2 related factor 2 (Nrf2), catalase (CAT), superoxide dismutase (SOD), Caspase 3, Caspase 8 and B-cell lymphoma-2 (Bcl2) genes all decreased significantly, the mRNA expression of HSP 70, HSP 90, interleukin-10 (IL-10), I-kappa-B-alpha (IkBα), kelch-1ike ECH- associated protein 1 (Keap1) and bcl2-associated X (Bax) genes all increased significantly (P < 0.05). However, the growth performance, serum biochemical indexes and mRNA expression of most genes in largemouth bass showed a correction trend after Ala-Gln addition, but still did not reach the level of control group. These results showed that dual stress of density and flow rate reduced growth and serum biochemical parameters in largemouth bass and increased the adverse expression of stress-related genes, while exogenous addition of Ala-Glu could somewhat ameliorate the negative effects of dual stress on largemouth bass.

Our study aimed to investigate the effects of alprostadil and Salvia miltiorrhizaextract on myocardial ischemia-reperfusion injury (IRI) and related underlying molecular mechanisms.

Endogenous guanidino compounds (GCs), nitrogen-containing metabolites, have very important physiological activities and participate in biochemical processes. Therefore, accurately characterizing the distribution of endogenous GCs and monitoring their concentration variations are of great significance. In this work, a new derivatization reagent, 4,4′-bis[3-(dimethylamino)propyl]benzyl (BDMAPB), with isotope-coded reagents was designed and synthesized for doubly charged labeling of GCs. BDMAPB-derivatized GCs not only promote the MS signal but also form multicharged quasimolecular ions and abundant fragment ions. With this reagent, an isotope-coded doubly charged labeling (ICDCL) strategy was developed for endogenous GCs with high-resolution liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF MS). The core of this methodology is a 4-fold multiplexed set of [d0]-/[d4]-/[d8]-/[d12]-BDMAPB that yields isotope-coded derivatized GCs. Following a methodological assessment, good linear responses in the range of 25 nM to 1 μM with correlation coefficients over 0.99 were achieved. The limit of detection and the limit of quantitation were below 5 and 25 nM, respectively. The intra- and interday precisions were less than 18%, and the accuracy was in the range of 77.3–122.0%. The percentage recovery in tissues was in the range of 85.1–113.7%. The results indicate that the developed method facilitates long-term testing and ensures accuracy and reliability. Finally, the method was applied for the simultaneous analysis of endogenous GCs in four types of lung tissues (solid adenocarcinoma, solid squamous-cell carcinoma, ground-glass carcinoma, and paracancerous tissues) for absolute quantification, nontargeted screening, and metabolic difference analysis. It is strongly believed that ICDCL combined with isotope-coded BDMAPB will benefit the analysis and study of endogenous GCs.

The mitochondrial DNA G-quadruplex (mtDNA G4) is a potential regulatory element for the regulation of mitochondrial functions; however, its relevance and specific roles in diseases remain largely unknown. Here, we engineered a set of chemical probes, including MitoISCH, an mtDNA G4-specific fluorescent probe, together with MitoPDS, a mitochondria-targeted G4-stabilizing agent, to thoroughly investigate mtDNA G4s. Using MitoISCHto monitor previously intractable dynamics of mtDNA G4s, we surprisingly found that their formation was prevalent only in endothelial and cancer cells that rely on glycolysis for energy production. Consistent with this, promotion of mtDNA G4 folding by MitoPDSin turn caused glycolysis-related gene activation and glycolysis enhancement. Remarkably, this close relationship among mtDNA G4s, glycolysis, and cancer cells further allowed MitoISCHto accumulate in tumors and label them in vivo. Our work reveals an unprecedented link between mtDNA G4s and cell glycolysis, suggesting that mtDNA G4s may be a novel cancer biomarker and therapeutic target deserving further exploration.

Because of the lack of facile and accurate methods to track stress granule (SG) dynamics in live cells and in vivo, in-depth studies of the biological roles of this attractive membraneless organelle have been limited. Herein, we report the first small-molecule probe, TASG, for the selective, convenient and real-time monitoring of SGs. This novel molecule can simultaneously bind to SG RNAs, the core SG protein G3BP1, and their complexes, triggering a significant enhancement in fluorescence intensity, making TASGbroadly applicable to SG imaging under various stress conditions in fixed and live cells, ex vivoand in vivo. Using TASG, the complicated endogenous SG dynamics were revealed in both live cells and C. elegans. Collectively, our work provides an ideal probe that has thus far been absent in the field of SG investigations. We anticipate that this powerful tool may create exciting opportunities to investigate the underlying roles of SGs in different organisms.

Byline: Xiu-Jun. Chen, Jian-Ping. Xiao, Xiang-Pan. Li, Xue-Song. Jiang, Ye. Zhang Objective: To explore the outcome and prognostic factors of recursive partitioning analysis (RPA) Class III brain metastatic patients treated [...]

Circular RNAs (circRNAs) appear to be significant modulators in various physiological processes. Recently, it is found that circRNA_101996 exerts important roles in various cancers. Our previous studies showed that circRNA_101996 promoted cervical cancer growth and metastasis by regulating miR‐8075/TPX2. However, the potential regulatory role of circRNA_101996 in cervical cancer still needs further investigation. Our results in this study suggested that circRNA_101996 was over‐expressed in cervical cancer patients. circRNA_101996 up‐regulation remarkably assisted cell proliferation, cell cycle progression, and cell migration in cervical cancer, while circRNA_101996 knockdown exerted the inverse effects. The molecular investigations indicated that circRNA_101996 could increase the expression level of miR‐1236‐3p, tripartite motif‐containing 37 (TRIM37), through binding to miR‐1236‐3p and reducing its expression. Moreover, in vivo results demonstrated that circRNA_101996 shRNA can function as a tumor suppressor through down‐regulating TRIM37 in cervical cancer. In conclusion, our data indicated that circRNA_101996/miR‐1236‐3p/TRIM37 axis accelerated cervical cancer development, providing novel insights into cervical cancer diagnosis and treatment.

Kahane, Yehuda and Haim Levy, 1975, Regulation in the Insurance Industry: Determination of Premiums in Automobile Insurance, Journal of Risk and Insurance, 42:117-132. Keeton, Robert E. and Jeffrey O'Connell, 1965, [...]

Using heavy oil and three SDA products as precursors, we synthesized highly fluorescent multi-color carbon dots (CDs) by hydrothermal method and further used the CDs in macrophage labeling.

Acidity is an important property of particulate matter (PM) in the atmosphere, but its association with PM toxicity remains unclear. Here, this study quantitively reports the effect of the acidity level on PM toxicity via pH-control experiments and cellular analysis. Oxidative stress and cytotoxicity potencies of acidified PM samples at pH of 1–2 were up to 2.8–5.2 and 2.1–13.2 times higher than those at pH of 8–11, respectively. The toxic potencies of PM samples from real-world smoke plumes at the pH of 2.3 were 9.1–18.2 times greater than those at the pH of 5.6, demonstrating a trend similar to that of acidified PM samples. Furthermore, the impact of acidity on PM toxicity was manifested by promoting metal dissolution. The dramatic increase by 2–3 orders of magnitude in water-soluble metal content dominated the variation in PM toxicity. The significant correlation between sulfate, the pH value, water-soluble Fe, IC20, and EC1.5(p< 0.05) suggested that acidic sulfate could enhance toxic potencies by dissolving insoluble metals. The findings uncover the superficial association between sulfate and adverse health outcomes in epidemiological research and highlight the control of wet smoke plume emissions to mitigate the toxicity effects of acidity.

This paper identifies a potential gap between time preference and intertemporal choices such as time discounting tasks: The intertemporal choices could be partly driven by a biased perception of time and thus may not completely reveal actual time preference. To test this, we explore the causal relationship between time perception and intertemporal choices by conducting a laboratory experiment in which cognitive load is used as a stimulating instrument to induce differences in time perception. We establish that the perceived time lengths for subjects with high cognitive load are shorter than those with low cognitive load and that individuals who underestimate time appear more patient in their intertemporal choices. Mediation analyses show that time perception mediates a significant portion of cognitive load’s effect on intertemporal choices. Our study thus demonstrates that time preference identified by intertemporal choices might be confounded by potentially biased time perception, calling for improving suboptimal time-related economic decisions due to an individual’s misperception of how time flies.

A 23-year-old pregnant woman presented with headache and paroxysmal spasm of the right limb. She was born with a port-wine birthmark around the left eye frame. Magnetic resonance imaging revealed evidence of atrophy, calcification and vascular malformation in the left cerebral hemisphere. She was diagnosed with Sturge-Weber syndrome. She gave birth to a child without a port-wine birthmark through a caesarean section and her headache eased without surgical intervention of the intracranial vessel hyperplasia. This case suggests that pregnant women with SWS can deliver safely.

Hyperactivated KRAS mutations fuel tumorigenesis and represent attractive targets for cancer treatment. While covalent inhibitors have shown clinical benefits against the KRASG12Cmutant, advancements for non-G12C mutants remain limited, highlighting the urgent demand for pan-KRAS inhibitors. RNA G-quadruplexes (rG4s) in the 5′-untranslated region of KRASmRNA can regulate KRAS translation, making them promising targets for pan-KRAS inhibitor development. Herein, we designed and synthesized 50 novel coumarin-quinolinium derivatives, leveraging our previously developed rG4-specific ligand, QUMA-1. Notably, several compounds exhibited potent antiproliferative activity against cancer cells as pan-KRAS translation inhibitors. Among them, 15adisplayed exceptional capability in stabilizing KRASrG4s, suppressing KRAS translation, and consequently modulating MAPK and PI3K-AKT pathways. 15ainduced cell cycle arrest, prompted apoptosis in KRAS-driven cancer cells, and effectively inhibited tumor growth in a KRAS mutant xenograft model. These findings underscore the potential of 15aas a pan-KRAS translation inhibitor, offering a novel and promising approach to target various KRAS-driven cancers.

Osimertinib (AZD9291) has been widely used for the treatment of EGFR mutant non-small cell lung cancer. However, resistance to osimertinib is inevitable. In this study we elucidated the molecular mechanisms of resistance in osimertinib-resistant NCI-H1975/OSIR cells. We showed that NCI-H1975/OSIR cells underwent epithelial–mesenchymal transition (EMT), which conferred sensitivity to the GPX4 inhibitor 1S, 3R-RSL3 to induce ferroptotic cell death. The EMT occurrence resulted from osimertinib-induced upregulation of TGFβ2 that activated SMAD2. On the other hand, we revealed that NCI-H1975/OSIR cells were highly dependent on NF-κB pathway for survival, since treatment with the NF-κB pathway inhibitor BAY 11–7082 or genetic silence of p65 caused much greater cell death as compared with the parental NCI-H1975 cells. In NCI-H1975 cells, osimertinib activated NF-κB pathway, evidenced by the increased p65 nuclear translocation, which was abolished by knockdown of TGFβ2. In the cancer genome atlas lung adenocarcinoma data, TGFB2 transcript abundance significantly correlated with EMT-associated genes and NF-κB pathway. In addition, coexistence of EMT and activation of NF-κB pathway was observed in several NCI-H1975/OSIR clones. These findings shed new light on distinct roles of TGFβ2 in osimertinib-resistant cells and provide new strategies for treatment of this resistant status.

Fluorescence recovery after photobleaching (FRAP) has been used to study the dynamics of the cyanobacterial photosynthesis apparatus since 1997. Fluorescence recovery of cyanobacteria during FRAP was conventionally interpreted as a result of phycobilisome (PBS) diffusion on the surface of the thylakoid membrane. The mechanism of state transition in cyanobacteria has been widely attributed to PBS diffusion. However, in red algae, another PBS-containing group, the intrinsic photoprocess was found to contribute greatly to the fluorescence recovery of PBS, which raises questions concerning the role of FRAP in red algal PBS. Therefore, it is important to re-evaluate the nature of PBS fluorescence recovery in cyanobacteria. In the present study, four cyanobacterial strains with different phenotypes and PBS compositions were used to investigate their FRAP characteristics. Fluorescence recovery of PBS was observed in wholly photobleached cells in all four cyanobacterial strains, in which the contribution of PBS diffusion to the fluorescence recovery was not possible. Moreover, the fluorescence recovered in isolated PBSs and PBS-thylakoid membranes after photobleaching further demonstrated the intrinsic photoprocess nature of fluorescence recovery. These findings suggest that the intrinsic photoprocess contributed to the fluorescence recovery following photobleaching when measured by the FRAP method.

Byline: Xiang-Pan. Li, Jian-Ping. Xiao, Xiu-Jun. Chen, Xue-Song. Jiang, Ye. Zhang, Ying-Jie. Xu Objective: Patients with small-cell lung cancer (SCLC) are at high risk of developing brain metastases (BM). Fractionated [...]