MPCLCDA: predicting circRNA-disease associations by using automatically selected meta-path and contrastive learning.

Circular RNA (circRNA) is closely associated with human diseases. Accordingly, identifying the associations between human diseases and circRNA can help in disease prevention, diagnosis and treatment. Traditional methods are time consuming and laborious. Meanwhile, computational models can effectively predict potential circRNA-disease associations (CDAs), but are restricted by limited data, resulting in data with high dimension and imbalance. In this study, we propose a model based on automatically selected meta-path and contrastive learning, called the MPCLCDA model. First, the model constructs a new heterogeneous network based on circRNA similarity, disease similarity and known association, via automatically selected meta-path and obtains the low-dimensional fusion features of nodes via graph convolutional networks. Then, contrastive learning is used to optimize the fusion features further, and obtain the node features that make the distinction between positive and negative samples more evident. Finally, circRNA-disease scores are predicted through a multilayer perceptron. The proposed method is compared with advanced methods on four datasets. The average area under the receiver operating characteristic curve, area under the precision-recall curve and F1 score under 5-fold cross-validation reached 0.9752, 0.9831 and 0.9745, respectively. Simultaneously, case studies on human diseases further prove the predictive ability and application value of this method.

FLOWERING LOCUS T1 and TERMINAL FLOWER1 regulatory networks mediate flowering initiation in apple.

Flower bud formation is a critical process that directly determines yield and fruit quality in fruit crops. Floral induction is modulated by the balance between 2 flowering-related proteins, FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1); however, the mechanisms underlying the establishment and maintenance of this dynamic balance remain largely elusive. Here, we showed that in apple (Malus × domestica Borkh.), MdFT1 is predominantly expressed in spur buds and exhibits an increase in expression coinciding with flower induction; in contrast, MdTFL1 exhibited downregulation in apices during flower induction, suggesting that MdTFL1 has a role in floral repression. Interestingly, both the MdFT1 and MdTFL1 transcripts are directly regulated by transcription factor basic HELIX-LOOP-HELIX48 (MdbHLH48), and overexpression of MdbHLH48 in Arabidopsis (Arabidopsis thaliana) and tomato (Solanum lycopersicum) results in accelerated flowering. Binding and activation analyses revealed that MdbHLH48 functions as a positive regulator of MdFT1 and a negative regulator of MdTFL1. Further studies established that both MdFT1 and MdTFL1 interact competitively with MdWRKY6 protein to facilitate and inhibit, respectively, MdWRKY6-mediated transcriptional activation of target gene APPLE FLORICAULA/LFY (AFL1, an apple LEAFY-like gene), ultimately regulating apple flower bud formation. These findings illustrate the fine-tuned regulation of flowering by the MdbHLH48-MdFT1/MdTFL1-MdWRKY6 module and provide insights into flower bud formation in apples.

Ionic Current Saturation Enabled by Cation Gating Effect in Metal-Organic-Framework Membranes.

Ion transport through nanoporous two-dimensional (2D) membranes is predicted to be tunable by controlling the charging status of the membranes' planar surfaces, the behavior of which though remains to be assessed experimentally. Here we investigate ion transport through intrinsically porous membranes made of 2D metal-organic-framework layers. In the presence of certain cations, we observe a linear-to-nonlinear transition of the ionic current in response to the applied electric field, the behavior of which is analogous to the cation gating effect in the biological ion channels. Specifically, the ionic currents saturate at transmembrane voltages exceeding a few hundreds of millivolts, depending on the concentration of the gating cations. This is attributed to the binding of cations at the membranes' surfaces, tuning the charging states there and affecting the entry/exit process of translocating ions. Our work also provides 2D membranes as candidates for building nanofluidic devices with tunable transport properties.

Amino Acid Variation at Hemagglutinin Position 193 Impacts the Properties of H9N2 Avian Influenza Virus.

Despite active control strategies, including the vaccination program in poultry, H9N2 avian influenza viruses possessing mutations in hemagglutinin (HA) were frequently isolated. In this study, we analyzed the substitutions at HA residue 193 (H3 numbering) of H9N2 and investigated the impact of these mutations on viral properties. Our study indicated that H9N2 circulating in the Chinese poultry have experienced frequent mutations at HA residue 193 since 2013, with viruses that carried asparagine (N) being replaced by those with alanine (A), aspartic acid (D), glutamic acid (E), glycine (G), and serine (S), etc. Our results showed the N193G mutation impeded the multiple cycles of growth of H9N2, and although most of the variant HAs retained the preference for human-like receptors as did the wild-type N193 HA, the N193E mutation altered the preference for both human and avian-like receptors. Furthermore, these mutations substantially altered the antigenicity of H9N2 as measured by both monoclonal antibodies and antisera. In vivo studies further demonstrated that these mutations showed profound impact on viral replication and transmission of H9N2 in chicken. Viruses with D, E, or S at residue 193 acquired the ability to replicate in lungs of the infected chickens, whereas virus with G193 reduced its transmissibility in infected chickens to those in direct contact. Our findings demonstrated that variations at HA residue 193 altered various properties of H9N2, highlighting the significance of the continued surveillance of HA for better understanding of the etiology and effective control of H9N2 in poultry. IMPORTANCE H9N2 are widespread and have sporadically caused clinical diseases in humans. Extensive vaccinations in poultry helped constrain H9N2; however, they might have facilitated the evolution of the virus. It is therefore of importance to monitor the variation of the circulating H9N2 and evaluate its risk to both veterinary and public health. Here, we found substitutions at position 193 of HA from H9N2 circulated since 2013 and assessed the impact of several mutations on viral properties. Our data showed these mutations resulted in substantial antigenic change. N193E altered the binding preference of HA for human-like to both avian and human-like receptors. More importantly, N193G impaired the growth of H9N2 and its transmission in chickens, whereas mutations from N to D, E, and S enhanced the viral replication in lungs of chickens. Our study enriched the knowledge about H9N2 and may help implement an effective control strategy for H9N2.

Identification of miRNA-disease associations via deep forest ensemble learning based on autoencoder.

Increasing evidences show that the occurrence of human complex diseases is closely related to microRNA (miRNA) variation and imbalance. For this reason, predicting disease-related miRNAs is essential for the diagnosis and treatment of complex human diseases. Although some current computational methods can effectively predict potential disease-related miRNAs, the accuracy of prediction should be further improved. In our study, a new computational method via deep forest ensemble learning based on autoencoder (DFELMDA) is proposed to predict miRNA-disease associations. Specifically, a new feature representation strategy is proposed to obtain different types of feature representations (from miRNA and disease) for each miRNA-disease association. Then, two types of low-dimensional feature representations are extracted by two deep autoencoders for predicting miRNA-disease associations. Finally, two prediction scores of the miRNA-disease associations are obtained by the deep random forest and combined to determine the final results. DFELMDA is compared with several classical methods on the The Human microRNA Disease Database (HMDD) dataset. Results reveal that the performance of this method is superior. The area under receiver operating characteristic curve (AUC) values obtained by DFELMDA through 5-fold and 10-fold cross-validation are 0.9552 and 0.9560, respectively. In addition, case studies on colon, breast and lung tumors of different disease types further demonstrate the excellent ability of DFELMDA to predict disease-associated miRNA-disease. Performance analysis shows that DFELMDA can be used as an effective computational tool for predicting miRNA-disease associations.

Explaining citizens' plastic reduction behavior with an extended theory of planned behavior model: An empirical study in Switzerland.

The growing volume of plastic waste resulting from human activities is suffocating our planet. To combat this escalating issue, this study delves into the formation of plastic reduction behavior among Swiss citizens using an extended theory of planned behavior model. Through an online survey, the study obtained 149 valid responses, which were analyzed using partial least squares-based structural equation modeling. The results indicate a significant and strong relationship between plastic risk perception and attitudes towards plastic reduction and environmental protection. Notably, the cognitive dimension (ß = 0.802, p = 0.000) of plastic risk perception exhibits a tighter and stronger association with attitude compared to the emotional dimension (ß = 0.406, p = 0.000). Among the three variables in the theory of planned behavior model, perceived behavioral control (ß = 0.384, p = 0.000) emerges as the strongest determinant of behavioral willingness for plastic reduction. It is followed by attitude (ß = 0.214, p = 0.030). However, no significant relationship is observed between subjective norm and behavioral willingness for plastic reduction (ß = 0.07, p = 0.292). Finally, attitude fully mediates the relationship between plastic risk perception and behavioral willingness for plastic reduction. Theoretical and managerial implications are discussed.

Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection.

Genital Chlamydia trachomatis infection remains a major health issue as it causes severe complications including pelvic inflammatory disease, ectopic pregnancy and infertility in females as a result of infection-associated chronic inflammation. Podoplanin, a transmembrane receptor, has been previously reported on inflammatory macrophages. Thus, strategies that specifically target podoplanin might be able to reduce local inflammation. This study investigated the expression level and function of podoplanin in a C. trachomatis infection model. C57BL/6 mice infected with the mouse pathogen Chlamydia muridarum were examined intermittently from days 1 to 60 using flow cytometry analysis. Percentages of conventional macrophages (CD11b+ CD11c- F4/80+ ) versus inflammatory macrophages (CD11b+ CD11c+ F4/80+ ), and the expression of podoplanin in these cells were investigated. Subsequently, a podoplanin-knockout RAW264.7 cell was used to evaluate the function of podoplanin in C. trachomatis infection. Our findings demonstrated an increased CD11b+ cell volume in the spleen at day 9 after the infection, with augmented podoplanin expression, especially among the inflammatory macrophages. A large number of podoplanin-expressing macrophages were detected in the genital tract of C. muridarum-infected mice. Furthermore, analysis of the C. trachomatis-infected patients demonstrated a higher percentage of podoplanin-expressing monocytes than that in the noninfected controls. Using an in vitro infection in a transwell migration assay, we identified that macrophages deficient in podoplanin displayed defective migratory function toward C. trachomatis-infected HeLa 229 cells. Lastly, using immunoprecipitation-mass spectrometry method, we identified two potential podoplanin interacting proteins, namely, Cofilin 1 and Talin 1 actin-binding proteins. The present study reports a role of podoplanin in directing macrophage migration to the chlamydial infection site. Our results suggest a potential for reducing inflammation in individuals with chronic chlamydial infections by targeting podoplanin.

Chlamydia trachomatis plasmid-encoding Pgp3 protein induces secretion of distinct inflammatory signatures from HeLa cervical epithelial cells.

BACKGROUND: Genital Chlamydia trachomatis infection is the most common bacterial sexual transmitted disease that causes severe complications including pelvic inflammatory disease, ectopic pregnancy, and infertility in females. The Pgp3 protein encoded by C. trachomatis plasmid has been speculated to be an important player in chlamydial pathogenesis. However, the precise function of this protein is unknown and thus remains to be thoroughly investigated. METHODS: In this study, we synthesized Pgp3 protein for in vitro stimulation in the Hela cervical carcinoma cells. RESULTS AND CONCLUSION: We showed that Pgp3 induced prominent expression of host inflammatory cytokine genes including interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and chemokine C-X-C motif ligand 1 (CXCL1), implying a possible role of Pgp3 in modulating the inflammatory reaction in the host.

Peptidoglycan recognition protein SC (PGRP-SC) shapes gut microbiota richness, diversity and composition by modulating immunity in the house fly Musca domestica.

The gastrointestinal tract of all animals, including insects, is colonized by a remarkable array of microorganisms which are referred to collectively as the gut microbiota. The hosts establish mutually beneficial interactions with the gut microbiota. However, the mechanisms shaping these interactions remain to be better understood. Here, we investigated the roles of Musca domestica peptidoglycan recognition protein SC (MdPGRP-SC), a secreted pattern recognition receptor, in shaping the gut microbial community structure by using biochemical and high-throughput sequencing approaches. The recombinant MdPGRP-SC (rMdPGRP-SC) could strongly bind various pathogen-associated molecular patterns (PAMPs) including peptidoglycan, lipopolysaccharide and D-galactose, and exhibited mild affinity to ß-1, 3-glucan and D-mannose. Meanwhile, rMdPGRP-SC could also bind different kinds of microorganisms, including gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and yeast (Pichia pastoris). rMdPGRP-SC also exhibited weak antibacterial activity against Bacillus subtilis. Knockdown of MdPGRP-SC by RNAi reduced the persistence of ingested E. coli and a load of indigenous microbiota in the larval gut significantly. In addition, depleted MdPGRP-SC also altered the gut microbiota composition and led to increased ratios of Gram-negative bacteria. We hypothesize that MdPGRP-SC is involved in maintaining gut homeostasis by modulating the immune intensity of the gut through multiple mechanisms, including degrading or neutralizing various PAMPs and selectively suppressing the growth of some bacteria. Considering the functional conservation of the peptidoglycan recognition protein (PGRP) family in insects, the catalytic PGRPs might be promising candidate targets not only for pest and vector control but also for the treatment of bacterial infection in insect farming.

RhoA suppresses pseudorabies virus replication in vitro.

The porcine pseudorabies virus (PRV) is one of the most devastating pathogens and brings great economic losses to the swine industry worldwide. Viruses are intracellular parasites that have evolved numerous strategies to subvert and utilize different host processes for their life cycle. Among the different systems of the host cell, the cytoskeleton is one of the most important which not only facilitate viral invasion and spread into neighboring cells, but also help viruses to evade the host immune system. RhoA is a key regulator of cytoskeleton system that may participate in virus infection. In this study, we characterized the function of RhoA in the PRV replication by chemical drugs treatment, gene knockdown and gene over-expression strategy. Inhibition of RhoA by specific inhibitor and gene knockdown promoted PRV proliferation. On the contrary, overexpression of RhoA or activation of RhoA by chemical drug inhibited PRV infection. Besides, our data demonstrated that PRV infection induced the disruption of actin stress fiber, which was consistent with previous report. In turn, the actin specific inhibitor cytochalasin D markedly disrupted the normal fibrous structure of intracellular actin cytoskeleton and decreased the PRV replication, suggesting that actin cytoskeleton polymerization contributed to PRV replication in vitro. In summary, our data displayed that RhoA was a host restriction factor that inhibited PRV replication, which may deepen our understanding the pathogenesis of PRV and provide further insight into the prevention of PRV infection and the development of anti-viral drugs.

Palladium-catalysed site-selective arene ortho C-H fluoroalkoxylation of 4-aryl-pyrrolo[2,3-d]pyrimidines.

A palladium-catalysed direct arene C-H fluoroalkoxylation of 4-aryl-pyrrolo[2,3-d]pyrimidine derivatives with fluorinated alcohols is described. Highly site-selective mono- or bis-fluoroalkoxylation can be achieved by tuning the reaction conditions, affording various fluoroalkoxylated pyrrolo[2,3-d]pyrimidine derivatives in moderate to good yields, which offer rational tailoring of their biological activity for their application in the field of pharmaceutical chemistry.

Defensive Specialized Metabolites from the Latex of Euphorbia jolkinii.

Plant latex is sequestered in laticiferous structures and exuded immediately from damaged plant tissues. The primary function of plant latex is related to defense responses to their natural enemies. Euphorbia jolkinii Boiss. is a perennial herbaceous plant that greatly threaten the biodiversity and ecological integrity of northwest Yunnan, China. Nine triterpenes (1-9), four non-protein amino acids (10-13) and three glycosides (14-16) including a new isopentenyl disaccharide (14), were isolated and identified from the latex of E. jolkinii. Their structures were established on the basis of comprehensive spectroscopic data analyses. Bioassay revealed that meta-tyrosine (10) showed significant phytotoxic activity, inhibiting root and shoot growth of Zea mays, Medicago sativa, Brassica campestris, and Arabidopsis thaliana, with EC50 values ranging from 4.41 ± 1.08 to 37.60 ± 3.59 µg/mL. Interestingly, meta-tyrosine inhibited the root growth of Oryza sativa, but promoted their shoot growth at the concentrations below 20 µg/mL. meta-Tyrosine was found to be the predominant constituent in polar part of the latex extract from both stems and roots of E. jolkinii, but undetectable in the rhizosphere soil. In addition, some triterpenes showed antibacterial and nematicidal effects. The results suggested that meta-tyrosine and triterpenes in the latex might function as defensive substances for E. jolkinii against other organisms.

Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson's disease mouse model through activating GHS-R1a/D2R heterodimers.

Growth hormone secretagogue receptor 1a (GHS-R1a) is an important G protein-coupled receptor (GPCR) that regulates a variety of functions by binding to ghrelin. It has been shown that the dimerization of GHS-R1a with other receptors also affects ingestion, energy metabolism, learning and memory. Dopamine type 2 receptor (D2R) is a GPCR mainly distributed in the ventral tegmental area (VTA), substantia nigra (SN), striatum and other brain regions. In this study we investigated the existence and function of GHS-R1a/D2R heterodimers in nigral dopaminergic neurons in Parkinson's disease (PD) models in vitro and in vivo. By conducting immunofluorescence staining, FRET and BRET analyses, we confirmed that GHS-R1a and D2R could form heterodimers in PC-12 cells and in the nigral dopaminergic neurons of wild-type mice. This process was inhibited by MPP+ or MPTP treatment. Application of QNP (10 µM) alone significantly increased the viability of MPP+-treated PC-12 cells, and administration of quinpirole (QNP, 1 mg/kg, i.p. once before and twice after MPTP injection) significantly alleviated motor deficits in MPTP-induced PD mice model; the beneficial effects of QNP were abolished by GHS-R1a knockdown. We revealed that the GHS-R1a/D2R heterodimers could increase the protein levels of tyrosine hydroxylase in the SN of MPTP-induced PD mice model through the cAMP response element binding protein (CREB) signaling pathway, ultimately promoting dopamine synthesis and release. These results demonstrate a protective role for GHS-R1a/D2R heterodimers in dopaminergic neurons, providing evidence for the involvement of GHS-R1a in PD pathogenesis independent of ghrelin.

Oxidation of 1,3-diphenylguanidine (DPG) by goethite activated persulfate: Mechanisms, products identification and reaction sites prediction.

As emerging pollutants continue to be discovered, studies on the degradation behavior of emerging pollutants have proliferated, but few studies have focused on the reactivity of the new pollutants themselves. The work investigated the oxidation of a representative roadway runoff-derived organic contaminant, 1,3-diphenylguanidine (DPG) by goethite activated persulfate (PS). DPG exhibited the highest degradation rate (kd = 0.42 h-1) with present of PS and goethite at pH 5.0, then started to decrease with increasing pH. Chloride ion inhibited DPG degradation by scavenging HO·. Both HO· and SO4-· were generated in goethite activated PS system. Competitive kinetic experiments and flash photolysis experiments were conducted to investigate free radical reaction rate. The second-order reaction rate constants for DPG reacting with HO· and SO4-· were quantified (kDPG + HO·,kDPG + SO4-·), which both reached above 109 M-1 s-1. Chemical structures of five products were identified, four of them were previously detected in DPG photodegradation, bromination and chlorination processes. By density functional theory (DFT) calculations, ortho- and para- C were more easily attacked by both HO· and SO4-·. Abstraction of H on N by HO· and SO4-· were the favorable pathways, and the product TP-210 might be generated by cyclization of DPG radical from abstraction of H on N (3). The results of this study help us to better understand the reactivity of DPG with SO4-· and HO·.

The roles of stress-induced premature senescence and Akt/FoxO1 signaling in periapical lesions.

OBJECTIVES: There is little knowledge about oxidative stress-induced senescence involvement in apical periodontitis. Here, we explored its molecular mechanism in periapical lesions. METHODS: Ten cases of radicular cysts and five cases of periapical granulomas were randomly selected. Immunohistochemical analysis was performed to detect the expression and correlation between Senescence-associated factor polymerase I and transcript release factor (PTRF) and Akt/FoxO1 signaling. Human periodontal ligament cells (hPDLCs) pretreated with LY294002 were exposed to H2 O2 -induced oxidative stress conditions and then cell proliferation, senescence, apoptosis, and associated signaling were evaluated by EdU labeling, ß-galactosidase assay, RT-qPCR, and western blot analysis, respectively. RESULTS: Polymerase I and transcript release factor and Akt/FoxO1 signaling were more frequently expressed in the radicular cyst than in periapical granulomas. Notably, cells in radicular cysts showed Akt activation, FoxO1 phosphorylation, and cytoplasmic translocation. In vitro, prominent H2 O2 -induced senescence was observed in hPDLCs. LY294002, a PI3K inhibitor, attenuated the expression levels of senescence (Klotho, P16INK4), apoptosis (Bad, Fas), phosphorylated Akt, and phosphorylated FoxO1; however, did not affect cell proliferation. CONCLUSIONS: Our data indicated that senescence is present in clinical periapical lesions, and Akt/FoxO1 signaling is involved in the H2 O2 -induced cellular senescence, which could serve as a potential therapeutic target.

Endophytic Bacillus sp. AP10 harboured in Arabis paniculata mediates plant growth promotion and manganese detoxification.

Phytoremediation of heavy metal-polluted soils assisted by plant-associated endophytes, is a suitable method for plant growth and manganese (Mn) removal in contaminated soils. This investigation was conducted to evaluate the Mn-resistant endophytic resources of the Mn hyperaccumulator Arabis paniculata and their functions in the phytoremediation of Mn2+ toxicity. This study isolated an endophytic bacterium with high Mn resistance and indole-3-acetic acid (IAA) production form A. paniculata and identified it as Bacillus sp. AP10 using 16 S rRNA gene sequencing analysis. The effects of Bacillus sp. AP10 on the alleviation of Mn2+ toxicity in Arabidopsis thaliana seedlings and the molecular mechanisms were further investigated using biochemical tests and RNA-seq analysis. Under Mn2+ stress, Bacillus sp. AP10 increased the biomass, chlorophyll content and the translocation factor (TF) values of Mn in the aerial parts, while decreased the malondialdehyde (MDA) content of A. thaliana seedlings compared with that of control plants. The differentially expressed genes (DEGs) and enrichment analysis showed that Bacillus sp. AP10 could significantly increase the expression of key genes involved in cell-wall loosening, which may improve plant growth under Mn stress. Superoxide dismutase (SOD)-encoding genes were detected as DEGs after AP10 treatment. Moreover, AP10 regulated the expression of genes responsible for phenylpropanoid pathway, which may promote antioxidant flavonoids accumulation for reactive oxygen species (ROS) scavenging to improve Mn tolerance. The activation of ATP-binding cassette (ABC) transporter gene expression especially ABCB1 after AP10 stimulation, explained the elevation of metal ion binding or transport related to enhanced Mn accumulation in plants. Futhermore, AP10 might alleviate Mn toxicity through enhancing abscisic acid (ABA) responsive gene expression and ABA biosynthesis. These findings provide new insights into the functions and regulatory mechanism of Bacillus sp. AP10 in promoting plant growth, and tolerance, improving Mn accumulation and alleviating Mn2+ toxicity in plants. The application of Bacillus sp. AP10 as potential phytoremediators may be a promising strategy in Mn2+ contaminated fields. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

First Report of Pestalotiopsis trachicarpicola Causing Leaf Blight on Panax notoginseng in China.

Panax notoginseng (Burkill) F. H. Chen ex C. Y. Wu & K.M. Feng is a Chinese herbal medicinal plant for treating diseases of the central nervous system and cardiovascular system, widely used as a medicine and health-care product. In May 2022, leaf blight disease was found on leaves of 1-year-old P. notoginseng in the plantings （27.904°N, 112.918°E） of Xiangtan City (Hunan) with an area of 104 m2. Over 400 plants were investigated, up to 25% of the plants were symptomatic. From the margin of the leaf, the initial symptoms of water-soaked chlorosis and following dry yellow with slight shrinkage appeared. Later, leaf shrinkage became serious and chlorosis enlarged gradually, leading to leaf death and abscission. To identify the causal agent, 20 leaf lesions (4 mm2) collected from 20 individual 1-year-old plants were sterilized with 75% ethanol for 10 s, 5% NaOCl for 10 s, rinsed in sterilized water three times, placed on potato dextrose agar (PDA) with lactic acid (0.125%) for inhibition the growth of bacteria, and incubated at 28°C for 7 days (Fang, 1998). Five isolates were obtained from 20 leaf lesions of different plants with the isolation rate of 25% and purified by single sporing, which have similar colony and conidia morphology characteristics. One isolate PB2-a was selected randomly for further identification. Colonies of PB2-a on PDA were white with cottony mycelium, developing concentric circles (top view) or light yellow (back view). Conidia (23.1 ± 2.1 × 5.7 ± 0.8 µm, n=30)were fusiform, straight or slightly curved and contained conic basal cell, three light brown median cells and hyaline conic apical cell with appendages. The rDNA internal transcribed spacer (ITS), the translation elongation factor 1-alpha (tef1), and the ß-tubulin (TUB2) genes were amplified from genomic DNA of PB2-a using primers ITS4/ITS5 (White et al. 1990), EF1-526F/EF1-1567R (Maharachchikumbura et al. 2012), and Bt2a/Bt2b (Glass and Donaldson, 1995; O'Donnell and Cigelnik, 1997), respectively. BLAST search of sequenced ITS (OP615100), tef1 (OP681464) and TUB2 (OP681465) exhibited > 99% identity with the type strain of Pestalotiopsis trachicarpicola OP068 (JQ845947, JQ845946 and JQ845945). Phylogenetic tree of the concatenated sequences was constructed based on the maximum-likelihood method using MEGA-X. Isolate PB2-a was identified as P. trachicarpicola based on morphological and molecular data (Maharachchikumbura et al. 2011; Qi et al. 2022). PB2-a was tested for pathogenicity three times to confirm Koch's postulates. Twenty healthy leaves on 20 1-year-old plants were punctured with sterile needles and inoculated with 50 µl of conidial suspension (1×106 conidia/ml). The controls were inoculated with sterile water. All plants were placed in a greenhouse at 25°C under 80% relative humidity. After 7 days, all inoculated leaves developed leaf blight symptoms identical to those described above, whereas the control plants kept healthy. P. trachicarpicola were reisolated from infected leaves, and identical to those of the originals based on the colony characteristics and the sequenced data of ITS, tef1 and TUB2. P. trachicarpicola was reported as a pathogen of leaf blight on Photinia fraseri (Xu et al. 2022). To our knowledge, this is the first report of P. trachicarpicola causing leaf blight on P. notoginseng in Hunan, China. Leaf blight is one of the destructive diseases in P. notoginseng production, identification of the pathogen will be useful to develop effective disease management and protect P. notoginseng, a medical plant with economic value.

Predictors of self-care behaviour trajectories in patients with chronic obstructive pulmonary disease: A latent class growth analysis.

AIMS AND OBJECTIVES: To explore the trajectories of self-care behaviours in patients with chronic obstructive pulmonary disease based on the latent class growth model and investigate the predictors of each trajectory based on the capability opportunity motivation and behaviour model. BACKGROUND: Studies on self-care behaviours of patients with chronic obstructive pulmonary disease are mainly cross-sectional surveys. However, little is known about longitudinal trends of self-care behaviours changes among those population. DESIGN: This was a prospective observational research performed according to STROBE Checklist. METHODS: One hundred and nineteen patients with chronic obstructive pulmonary disease were followed up at baseline, 3 and 6 months. Data collection included the scores of self-care behaviours, specific demographic and clinical characteristics, and scores for the predictors. A latent class growth model was used to explore the self-care behaviours trajectories. Multiple logistic regression analysis was conducted to identify predictors of self-care behaviours trajectories. RESULTS: Three trajectories in the self-care behaviours of patients with chronic obstructive pulmonary disease were found: a persistently negative trajectory, a maintenance trajectory after a slight increase and an active trajectory with a slow upward improvement in self-care behaviours. Medical insurance and access to medical resources were the predictors of self-care behaviours. CONCLUSION: The patients with poor medical resources and medical insurance are at high risk for the poor self-care behaviours and the negative trajectory. Thus, dynamic and individualised intervention should be continuously provided to ensure patients acquire adequate medical resources to comprehensively improve self-care behaviours. RELEVANCE TO CLINICAL PRACTICE: People with better self-care trajectory may be patients who receive more medical resources or have less financial burden, which will help with the early identification of high-risk patients with a negative self-care trajectory. Intervention guided by Behaviour Change Wheel Theory should be conducted dynamically for patients for patients with different trajectories. PATIENT OR PUBLIC CONTRIBUTION: Thank the patients and their families for their cooperation in data collecting in this study.

Prognostic analysis of stereotactic radiosurgery for brain metastases: a single-center retrospective study.

OBJECTIVES: Brain metastasis (BM) is a common event during the development of many cancers, and is also one of the main causes of death of patients. Stereotactic radiosurgery (SRS) is an effective treatment for BM. The prognostic effects of various clinical factors on local control (LC) and overall survival (OS) after SRS treatment are still unclear. The purpose of this study is to retrospectively analyze the intracranial progression free survival (iPFS) and OS of patients receiving SRS treatment, and explore the relationship between various clinical characteristics and patient prognosis. MATERIALS AND METHODS: We collected the clinical information of patients who were diagnosed with BM and received SRS treatment in our center between 2018 and 2021. Univariate and multivariate Cox regression analysis and KM analysis for iPFS and OS were conducted in R software to investigate the prognostic effects of clinical characteristics. RESULTS: In total, 183 patients that received SRS in our center were enrolled in the cohort. The median iPFS for all patients was 8.87 months (95% CI 6.9-10.6), and the median OS was 16.5 months (95% CI 12.9-20.7). BM number > = 5 (HR 1.965 [95% CI 1.381-2.796], p < 0.001, FDR-corrected p < 0.001) was found to be strong predictor for shorter iPFS and OS. Subgroup analysis showed that patients with cumulative intracranial tumor volume (CITV) > = 2.14 cm3 and number > = 5 had shortest iPFS (P < 0.001) and OS (P = 0.007), compared with other subgroups. For patients with more than 5 BMs, SRS plus whole brain radiotherapy (WBRT) could achieve better local control, compared with SRS alone group (P = 0.0357). Peripheral blood inflammation indicators were associated with the prognosis of BM patients in univariate Cox analysis, but not in multivariate Cox analysis. CONCLUSIONS: BM number is an independent prognostic factor for BM patients. The prognosis of patients in the subgroup with larger CITV and more BM is the worst. For patients with more than 5 BM, the combination of SRS and WBRT can improve the local control, but cannot prolong the OS.

Cinnamaldehyde Restores Ceftriaxone Susceptibility against Multidrug-Resistant Salmonella.

In recent years, infections caused by multidrug-resistant (MDR) bacteria have greatly threatened human health and imposed a burden on global public health. To overcome this crisis, there is an urgent need to seek effective alternatives to single antibiotic therapy to circumvent drug resistance and prevent MDR bacteria. According to previous reports, cinnamaldehyde exerts antibacterial activity against drug-resistant Salmonella spp. This study was conducted to investigate whether cinnamaldehyde has a synergistic effect on antibiotics when used in combination, we found that cinnamaldehyde enhanced the antibacterial activity of ceftriaxone sodium against MDR Salmonella in vitro by significantly reduced the expression of extended-spectrum beta-lactamase, inhibiting the development of drug resistance under ceftriaxone selective pressure in vitro, damaging the cell membrane, and affecting its basic metabolism. In addition, it restored the activity of ceftriaxone sodium against MDR Salmonella in vivo and inhibited peritonitis caused by ceftriaxone resistant strain of Salmonella in mice. Collectively, these results revealed that cinnamaldehyde can be used as a novel ceftriaxone adjuvant to prevent and treat infections caused by MDR Salmonella, mitigating the possibility of producing further mutant strains.