Lysine acetylation regulates the AT-rich DNA possession ability of H-NS.

H-NS, the histone-like nucleoid-structuring protein in bacteria, regulates the stability of the bacterial genome by inhibiting the transcription of horizontally transferred genes, such as the type III and type VI secretion systems (T3/T6SS). While eukaryotic histone posttranslational modifications (PTMs) have been extensively studied, little is known about prokaryotic H-NS PTMs. Here, we report that the acetylation of H-NS attenuates its ability to silence horizontally transferred genes in response to amino acid nutrition and immune metabolites. Moreover, LC-MS/MS profiling showed that the acetyllysine sites of H-NS and K120 are indispensable for its DNA-binding ability. Acetylation of K120 leads to a low binding affinity for DNA and enhances T3/T6SS expression. Furthermore, acetylation of K120 impairs the AT-rich DNA recognition ability of H-NS. In addition, lysine acetylation in H-NS modulates in vivo bacterial virulence. These findings reveal the mechanism underlying H-NS PTMs and propose a novel mechanism by which bacteria counteract the xenogeneic silencing of H-NS.

Xenogeneic nucleoid-associated EnrR thwarts H-NS silencing of bacterial virulence with unique DNA binding.

Type III and type VI secretion systems (T3/T6SS) are encoded in horizontally acquired genomic islands (GIs) that play crucial roles in evolution and virulence in bacterial pathogens. T3/T6SS expression is subjected to tight control by the host xenogeneic silencer H-NS, but how this mechanism is counteracted remains to be illuminated. Here, we report that xenogeneic nucleoid-associated protein EnrR encoded in a GI is essential for virulence in pathogenic bacteria Edwardsiella and Salmonella. We showed that EnrR plays critical roles in T3/T6SS expression in these bacteria. Various biochemical and genetic analyses demonstrated that EnrR binds and derepresses the promoter of esrB, the critical regulator of T3/T6SS, to promote their expression by competing with H-NS. Additionally, EnrR targets AT-rich regions, globally modulates the expression of ∼363 genes and is involved in various cellular processes. Crystal structures of EnrR in complex with a specific AT-rich palindromic DNA revealed a new DNA-binding mode that involves conserved HTH-mediated interactions with the major groove and contacts of its N-terminal extension to the minor groove in the symmetry-related duplex. Collectively, these data demonstrate that EnrR is a virulence activator that can antagonize H-NS, highlighting a unique mechanism by which bacterial xenogeneic regulators recognize and regulate foreign DNA.

Rim plate in the treatment of hyperextension tibial plateau fracture: surgical technique and a series of cases.

BACKGROUND: The existence of a "bare area" at the anterior plateau has been observed in cases where anteromedial and/or anterolateral proximal tibial locking plates are used for fixation in the treatment of hyperextension tibial plateau fractures (HTPF). The objective of this study is to introduce the rim plate fixation technique and evaluate its clinical efficacy. METHODS: A retrospective analysis was conducted on HTPF patients who underwent treatment with a combination of rim plate and proximal tibial locking plate at our hospital between April 2015 and December 2019. All patients were followed up for a minimum of one year. Open reduction and internal fixation were performed using anteromedial/posteromedial and/or anterolateral approaches for all cases. The surgical strategies employed for rim plate fixation were introduced, and both radiographic and clinical outcomes were assessed. RESULTS: Thirteen patients were enrolled in the study, with an average follow-up time of 4.3 years. Satisfactory reduction was achieved and radiographically maintained in all cases. Additionally, all patients exhibited satisfactory clinical functions, as evidenced by a mean hospital for special surgery (HSS) knee score of 96.2 ± 2.0 (range: 90-98). Furthermore, no wound complications or implant breakage were observed in this series. CONCLUSION: The combination of the rim plate and proximal tibial plate proved to be an effective fixation configuration, resulting in satisfactory clinical outcomes.

Agricultural Application Prospect of Fully Polarimetric and Quantification S-Band SAR Subsystem in Chinese High-Resolution Aerial Remote Sensing System.

The synthetic aperture radar (SAR) is a type of active radar that can obtain polarization scattering information of ground objects, which is an important supplement to optical remote sensing. This paper designs a high-precision quantitative SAR system that combines radiation and polarization calibration processing to achieve a subtle perception of the changes in soil moisture and straw coverage. In Yushu, Jilin, we conducted the first S-band agricultural remote sensing application experiment. The backscattering coefficient was measured under different water content and straw coverage conditions, and the results showed that the backscattering coefficient increased by about 2 dB and 6 dB, respectively. We estimated that the soil water content increased by about 0.01 cm3/cm3, which was consistent with the theoretical analysis. The polarization scattering characteristics also showed significant differences under different straw coverage. The results indicated that S-band quantitative SAR had an excellent response ability to water content and straw coverage, which provided a technical basis for further radar agricultural applications in the future.

Targeting FHL1 impairs cell proliferation and differentiation of acute myeloid leukemia cells.

The four and a half LIM domains 1 (FHL1) is considered to play important roles in tumors. This study aims to investigate the role and precise mechanisms of FHL1 in acute myeloid leukemia (AML). Here, we found that FHL1 was highly expressed in AML. CCK8, flow cytometry, and Western blot analysis of cell cycle-related proteins showed that overexpression of FHL1 promoted proliferation and accelerated cell cycle progression in HL-60 cells. Conversely, knockdown of FHL1 inhibited the proliferation and induced cell cycle arrest in KG-1 cells. Furthermore, knockdown of FHL1 promoted cell differentiation, while overexpression of FHL1 restrained all-trans retinoic acid induced cell differentiation in HL-60 cells, revealed by Wright-Giemsa staining and cell surface antigen analysis. Moreover, in vivo experiments revealed that depletion of FHL1 inhibited tumor growth and led to increased levels of CD11b and CD14. Here, we first identify an unexpected and important role of FHL1 that contributes to the AML progression, indicating that FHL1 may be a potential therapeutic target for AML.

Dissolution and Retention Process of CeO2 Nanoparticles in Soil with Dynamic Redox Conditions.

The time-course association of soil physicochemical properties and fate of CeO2 nanoparticles (NPs) is not well understood. This study for the first time investigated the dissolution and retention of CeO2 NPs (<25 nm) during soil short-term (6 h) and long-term (30 d) aging processes with dynamic redox conditions. Under the additional reductant-induced initial reductive condition, theoretically, up to 220‰ of Ce(IV) was temporarily reductively dissolved within 10 min, accompanied by a slow retention process (180 min) of Ce species in soil solutions. Conversely, the dissolution and slow retention of Ce species were not significant in soil solutions without added reductant. X-ray absorption near edge spectroscopy (XANES) shows that most of Ce species were present as Ce(IV) (94.0%-97.8%) in all soils after a long-term aging process. These results indicate that the soil dynamic redox conditions induced by oxidant/reductant intrinsically determined the different time-course dissolution and retention of CeO2 NPs, highlighting the occasional reductive condition in soil solution that may contribute to the migration and diffusion of Ce species. The time-course study should be also adopted to develop a comprehensive understanding of the nano-soil interactions.

An attenuated Vibrio harveyi surface display of envelope protein VP28 to be protective against WSSV and vibriosis as an immunoactivator for Litopenaeus vannamei.

Surface display can expose foreign antigenic protein on the surface of the vaccine vector, which is promising choice to elicit better immune responses. In this study, we apply this strategy to develop an immunoactivator by using a live attenuated Vibrio harveyi as an antigenic protein carrier with surface displayed VP28, a major envelope protein of white spot syndrome virus (WSSV), for two major pathogens of Litopenaeus vannamei. As a result, the immunoactivator showed self-limited growth and attenuation of virulence in shrimp via different inoculation routes either with single-repetitive dose or high dose. Moreover, either intramuscular injection or oral administration of the immunoactivator did not affect growth of shrimp body weight or cause pathologic changes. Additionally, the rapid immunoprotection was induced by the immunoactivator after administration for one week with highly relative percent survival (RPS) more than 90% against both V. harveyi and WSSV. Until 4 weeks post administration, the immunoactivator still possessed efficient immune effect with no less than 60% RPS for both pathogens. Totally, the attenuated V. harveyi surface displaying VP28 could be a potential immunoactivator for WSSV and vibriosis control in L. vannamei.

Raw Data-Based Motion Compensation for High-Resolution Sliding Spotlight Synthetic Aperture Radar.

For accurate motion compensation (MOCO) in airborne synthetic aperture radar (SAR) imaging, a high-precision inertial navigation system (INS) is required. However, an INS is not always precise enough or is sometimes not even included in airborne SAR systems. In this paper, a new, raw, data-based range-invariant motion compensation approach, which can effectively extract the displacements in the line-of-sight (LOS) direction, is proposed for high-resolution sliding spotlight SAR mode. In this approach, the sub-aperture radial accelerations of the airborne platform are estimated via a well-developed weighted total least square (WTLS) method considering the time-varying beam direction. The effectiveness of the proposed approach is validated by two airborne sliding spotlight C band SAR raw datasets containing different types of terrain, with a high spatial resolution of about 0.15 m in azimuth.

The Structure of ampG Gene in Pseudomonas aeruginosa and Its Effect on Drug Resistance.

In order to study the relationship between the structure and function of AmpG, structure, site-specific mutation, and gene complementary experiments have been performed against the clinical isolates of Pseudomonas aeruginosa. We found that there are 51 nucleotide variations at 34 loci over the ampG genes from 24 of 35 P. aeruginosa strains detected, of which 7 nucleotide variations resulted in amino acid change. The ampG variants with the changed nucleotides (amino acids) could complement the function of ampG deleted PA01 (PA01ΔG). The ampicillin minimum inhibitory concentration (MIC) of PA01ΔG complemented with 32 ampG variants was up to 512 µg/ml, similar to the original PA01 (P. aeruginosa PA01). Furthermore, site-directed mutation of two conservative amino acids (I53 and W90) showed that when I53 was mutated to 53S or 53T (I53S or I53T), the ampicillin MIC level dropped drastically, and the activity of AmpC ß-lactamase decreased as well. By contrast, the ampicillin MIC and the activity of AmpC ß-lactamase remained unchanged for W90R and W90S mutants. Our studies demonstrated that although nucleotide variations occurred in most of the ampG genes, the structure of AmpG protein in clinical isolates is stable, and conservative amino acid is necessary to maintain normal function of AmpG.

Chirality control of nonplanar lead phthalocyanine (PbPc) and its potential application in high-density storage: a theoretical investigation.

On single-crystal surfaces, achiral molecules may become chiral owing to confinement in two dimensions (2D). Metal phthalocyanines (MPcs) on Cu(001) and Ag(100) surfaces have exhibited a chiral electronic state. However, the chirality is not always desirable since crystal defects (grain boundaries) inevitably occur between two different chiral domains during the self-assembly of single layers. In this theoretical study, we propose to utilize metal(001) substrates with different electron configurations to mediate the azimuthal orientations of nonplanar PbPc. The results show that PbPc is chiral on Cu(001) with a partially filled s orbital (3d(10)4s(1)) but achiral on Pd(001) with a completely filled d orbital (4d(10)). The mechanism that PbPc prefers achiral azimuthal orientation rather than chiral orientation on Pd(001) is clarified. In addition, we predict that PbPc can form a (3 × 4) surface reconstruction. While it is used for data storage, the capacity is almost three orders of magnitude higher than the present storage materials.

[Study of a preoperative deep venous thrombosis predictor score for patients with fresh lower extremity fractures].

OBJECTIVE: To establish a preoperative deep venous thrombosis predictor score for patients with fresh lower extremity fractures by statistical analysis. METHODS: From January 2011 to December 2012, 1 705 patients with fresh lower extremity fractures were admitted to department of orthopaedic trauma, Beijing Jishuitan Hospital. They were randomly divided into two groups, the group 1 (n = 879) was used to screen risk factors and derived a predictive models based on logistic regression, the group 2 (n = 826) validated the models. RESULTS: Among the patients, there were 1 106 male and 599 female patients, with an average age of (50 ± 18) years.Variables related to preoperative deep venous thrombosis were age, length of time before surgery, cause of injury, low/high-energy injury, location of injury, history of cardiovascular and cerebrovascular diseases, and D-Dimer. The scores based on OR were: age ≤ 35 years: 1 point, > 35- < 65 years: 4 points, ≥ 65 years: 6 points; length of time before surgery, < 8 days:1 point, ≥ 8 days:2 points;low-energy injury:1 point, high energy injury:3 points;location of injury, foot and ankle:1 point, calf:3 points, around the knee: 5 points, femoral diaphysis and proximal femur:7 points, pelvis and acetabulum:4 points, ≥ 2 sites:6 point;history of cardiovascular and cerebrovascular diseases, yes:2 points, no:1 point. D-Dimer < 600 µg/L:1 point, ≥ 600 µg/L:3 points. Area under receiver operating characteristic curve was 0.79, critical point 15.5 points, sensitivity was 77.00%, specificity was 68.17%. CONCLUSION: The score can predict the preoperative deep venous thrombosis for patients with fresh lower extremity fractures, but limited.

The histone-like nucleoid-structuring protein encoded by the plasmid pMBL6842 regulates both plasmid stability and host physiology of Pseudoalteromonas rubra SCSIO 6842.

Plasmids orchestrate bacterial adaptation across diverse environments and facilitate lateral gene transfer within bacterial communities. Their presence can perturb host metabolism, creating a competitive advantage for plasmid-free cells. Plasmid stability hinges on efficient replication and partition mechanisms. While plasmids commonly encode histone-like nucleoid-structuring (H-NS) family proteins, the precise influence of plasmid-encoded H-NS proteins on stability remains elusive. In this study, we examined the conjugative plasmid pMBL6842, harboring the hns gene, and observed its positive regulation of parAB transcription, critical for plasmid segregation. Deletion of hns led to rapid plasmid loss, which was remedied by hns complementation. Further investigations unveiled adverse effects of hns overexpression on the bacterial host. Transcriptome analysis revealed hns's role in regulating numerous bacterial genes, impacting both host growth and swimming motility in the presence of the hns gene. Therefore, our study unveils the multifaceted roles of H-NS in both plasmid stability and host physiology, underscoring its biological significance and paving the way for future inquiries into the involvement of H-NS in horizontal gene transfer events.

Type III secretion system effector YfiD inhibits the activation of host poly(ADP-ribose) polymerase-1 to promote bacterial infection.

Modulation of cell death is a powerful strategy employed by pathogenic bacteria to evade host immune clearance and occupy profitable replication niches during infection. Intracellular pathogens employ the type III secretion system (T3SS) to deliver effectors, which interfere with regulated cell death pathways to evade immune defenses. Here, we reveal that poly(ADP-ribose) polymerase-1 (PARP1)-dependent cell death restrains Edwardsiella piscicida's proliferation in mouse monocyte macrophages J774A.1, of which PARP1 activation results in the accumulation of poly(ADP-ribose) (PAR) and enhanced inflammatory response. Moreover, E. piscicida, an important intracellular pathogen, leverages a T3SS effector YfiD to impair PARP1's activity and inhibit PAR accumulation. Once translocated into the host nucleus, YfiD binds to the ADP-ribosyl transferase (ART) domain of PARP1 to suppress its PARylation ability as the pharmacological inhibitor of PARP1 behaves. Furthermore, the interaction between YfiD and ART mainly relies on the complete unfolding of the helical domain, which releases the inhibitory effect on ART. In addition, YfiD impairs the inflammatory response and cell death in macrophages and promotes in vivo colonization and virulence of E. piscicida. Collectively, our results establish the functional mechanism of YfiD as a potential PARP1 inhibitor and provide more insights into host defense against bacterial infection.

Enhanced dosage delivery of pesticide under unmanned aerial vehicle condition for peanut plant protection: tank-mix adjuvants and formulation improvement.

BACKGROUND: Suspension concentrate (SC) is one of the most widely used formulations for agricultural plant protection. With the rapid development of unmanned aerial vehicle (UAV) plant protection, the problems of spray drift, droplet rebound and poor wettability in the application of SC from UAVs have attracted wide attention. Although some tank-mix adjuvants have been used to enhance dosage delivery for UAV, their effects and mechanisms are not fully clear, and few formulations are specifically designed for UAV. RESULTS: The type and concentration of tank-mix adjuvant affect the dosage delivery of SC. MO501 can significantly reduce DV<100µm , and inhibit droplet rebound on peanut leaves at concentrations ≥0.5%. Silwet 408 can achieve complete wetting and superspreading after adding ≥0.2% concentrations, but only ≥0.5% can inhibit rebound. XL-70 shows excellent regulation ability even at low concentration, and 0.2% concentration can simultaneously suppress impact and promote spreading. Besides, the formulation oil dispersion (OD) can significantly reduce the driftable fine fraction and inhibit rebound at dilution ratios of ≤250-fold, thus enhancing dosage delivery. CONCLUSION: SC is prone to rebound on hydrophobic leaf surfaces and shows poor wetting and spreading properties. Appropriate types and concentrations of tank-mix adjuvants and formulation improvement are two effective strategies for improving the dosage delivery of pesticides, whereas the addition of inappropriate adjuvants may cause potential risks instead. These findings provide guidance for the rational selection of tank-mix adjuvants and potential applications of OD for UAV plant protection. © 2023 Society of Chemical Industry.

Complete genome sequence and genome-wide transposon mutagenesis enable the determination of genes required for sodium hypochlorite tolerance and drug resistance in pathogen Aeromonas veronii GD2019.

Aeromonas veronii, a significant pathogen in aquatic environments, poses a substantial threat to both human and animal health, particularly in aquaculture. In this study, we isolated A. veronii strain GD2019 from diseased largemouth bass (Micropterus salmoides) during a severe outbreak of aeromonad septicemia in Guangdong Province, China. The complete genome sequence of A. veronii GD2019 revealed that GD2019 contains a single chromosome of 4703,168 bp with an average G+C content of 58.3%. Phylogenetic analyses indicated that GD2019 forms a separate sub-branch in A. veronii and comparative genomic analyses identified the existence of an intact Type III secretion system. Moreover, to investigate the genes that are required for the conditional fitness of A. veronii under various stresses, a high-density transposon insertion library in GD2019 was generated by a Tn5-based transposon and covers 6311 genomic loci including 4155 genes and 2156 intergenic regions. Leveraging this library, 630 genes were classified as essential genes for growth in rich-nutrient LB medium. Furthermore, the genes GE001863/NtrC and GE002550 were found to confer tolerance to sodium hypochlorite in A. veronii. GE002562 and GE002614 were associated with the resistance to carbenicillin. Collectively, our results provide abundant genetic information on A. veronii, shedding light on the pathogenetic mechanisms of Aeromonas.

Foregroundness-Aware Task Disentanglement and Self-Paced Curriculum Learning for Domain Adaptive Object Detection.

Unsupervised domain adaptive object detection (UDA-OD) is a challenging problem since it needs to locate and recognize objects while maintaining the generalization ability across domains. Most existing UDA-OD methods directly integrate the adaptive modules into the detectors. This integration procedure can significantly sacrifice the detection performances, though it enhances the generalization ability. To solve this problem, we propose an effective framework, named foregroundness-aware task disentanglement and self-paced curriculum adaptation (FA-TDCA), to disentangle the UDA-OD task into four independent subtasks of source detector pretraining, classification adaptation, location adaptation, and target detector training. The disentanglement can transfer the knowledge effectively while maintaining the detection performance of our model. In addition, we propose a new metric, i.e., foregroundness, and use it to evaluate the confidence of the location result. We use both foregroundness and classification confidence to assess the label quality of the proposals. For effective knowledge transfer across domains, we utilize a self-paced curriculum learning paradigm to train adaptors and gradually improve the quality of the pseudolabels associated with the target samples. Experiment results indicate that our method achieves state-of-the-art results on four cross-domain object detection tasks.

Identification of CaPs locus involving in purple stripe formation on unripe fruit, reveals allelic variation and alternative splicing of R2R3-MYB transcription factor in pepper (Capsicum annuum L.).

The purple color of unripe pepper fruit is attributed to the accumulation of anthocyanins. Only a few genes controlling the biosynthesis and regulation of anthocyanins have been cloned in Capsicum. In this study, we performed a bulked segregant analysis of the purple striped trait using an F2 population derived from a cross between the immature purple striped fruit line Chen12-4-1-1-1-1 and the normal green fruit line Zhongxian101-M-F9. We mapped the CaPs locus to an 841.39 kb region between markers M-CA690-Xba and MCA710-03 on chromosome 10. CA10g11690 encodes an R2R3-MYB transcription factor that is involved in the biosynthesis of anthocyanins as the best candidate gene. Overexpression and silencing in transformed tobacco (Nicotiana tabacum) lines indicated that CA10g11690 is involved in the formation of purple stripes in the exocarp. A comparison of parental sequences identified an insertion fragment of 1,926 bp in the second intron region of Chen12-4, and eight SNPs were detected between the two parents. Additionally, there were 49 single nucleotide polymorphic variations, two sequence deletions, and four sequence insertions in the promoter region. We found that CA10g11690 undergoes alternative splicing and generates different transcripts. Thus, the functional transcript of CA10g11690 appeared to be primarily involved in the development of purple phenotype in the exocarp. Our data provide new insight into the mechanism of anthocyanin biosynthesis and a theoretical basis for the future breeding of purple striped pepper varieties.

PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach.

In silico drug target identification, which includes many distinct algorithms for finding disease genes and proteins, is the first step in the drug discovery pipeline. When the 3D structures of the targets are available, the problem of target identification is usually converted to finding the best interaction mode between the potential target candidates and small molecule probes. Pharmacophore, which is the spatial arrangement of features essential for a molecule to interact with a specific target receptor, is an alternative method for achieving this goal apart from molecular docking method. PharmMapper server is a freely accessed web server designed to identify potential target candidates for the given small molecules (drugs, natural products or other newly discovered compounds with unidentified binding targets) using pharmacophore mapping approach. PharmMapper hosts a large, in-house repertoire of pharmacophore database (namely PharmTargetDB) annotated from all the targets information in TargetBank, BindingDB, DrugBank and potential drug target database, including over 7000 receptor-based pharmacophore models (covering over 1500 drug targets information). PharmMapper automatically finds the best mapping poses of the query molecule against all the pharmacophore models in PharmTargetDB and lists the top N best-fitted hits with appropriate target annotations, as well as respective molecule's aligned poses are presented. Benefited from the highly efficient and robust triangle hashing mapping method, PharmMapper bears high throughput ability and only costs 1 h averagely to screen the whole PharmTargetDB. The protocol was successful in finding the proper targets among the top 300 pharmacophore candidates in the retrospective benchmarking test of tamoxifen. PharmMapper is available at http://59.78.96.61/pharmmapper.

Ferroptosis promotes microtubule-associated protein tau aggregation via GSK-3ß activation and proteasome inhibition.

Ferroptosis is a form of regulated cell death resulting from iron accumulation and lipid peroxidation. Iron dyshomeostasis and peroxidation damage of neurons in some particular brain regions are closely related to a wide range of neurodegenerative diseases known as "tauopathies," in which intracellular aggregation of microtubule-associated protein tau is the common neuropathological feature. However, the relationship between ferroptosis and tau aggregation is not well understood. The current study demonstrates that erastin-induced ferroptosis can promote tau hyperphosphorylation and aggregation in mouse neuroblastoma cells (N2a cells). Moreover, ferroptosis inhibitor ferrostatin-1 can alleviate tau aggregation effectively. In-depth mechanism research indicates that activated glycogen synthase kinase-3ß (GSK-3ß) is responsible for the abnormal hyperphosphorylation of tau. More importantly, proteasome inhibition can exacerbate tau degradation obstacle and accelerate tau aggregation in the process of ferroptosis. Our results indicate that ferroptosis can lead to abnormal aggregation of tau protein and might be a promising therapeutic target of tauopathies.

Knockdown of ADORA2A antisense RNA 1 inhibits cell proliferation and enhances imatinib sensitivity in chronic myeloid leukemia.

Long non-coding RNAs (LncRNAs) exert important regulatory roles in chronic myeloid leukemia (CML). In this study, we aimed to investigate the potential role and molecular mechanism of lncRNA ADORA2A antisense RNA 1 (ADORA2A-AS1) in CML. We found that the expression of ADORA2A-AS1 was upregulated in CML. Further, knockdown of ADORA2A-AS1 inhibited the proliferation, induced apoptosis, arrested cell cycle, and enhanced imatinib sensitivity in CML cells. Besides, ADORA2A-AS1 promoted the expression of transforming growth factor-beta receptor 1 (TGFBR1) and ATP binding cassette subfamily C member 2 (ABCC2) via sponging miR-665, thereby exerting a tumor-promoting activity. Collectively, our results confirmed the oncogenic effect of ADORA2A-AS1 in CML, indicating that ADORA2A-AS1 is a promosing therapeutic target for CML.