m6Aexpress-enet: Predicting the regulatory expression m6A sites by an enet-regularization negative binomial regression model.

As the most abundant mRNA modification, m6A controls and influences many aspects of mRNA metabolism including the mRNA stability and degradation. However, the role of specific m6A sites in regulating gene expression still remains unclear. In additional, the multicollinearity problem caused by the correlation of methylation level of multiple m6A sites in each gene could influence the prediction performance. To address the above challenges, we propose an elastic-net regularized negative binomial regression model (called m6Aexpress-enet) to predict which m6A site could potentially regulate its gene expression. Comprehensive evaluations on simulated datasets demonstrate that m6Aexpress-enet could achieve the top prediction performance. Applying m6Aexpress-enet on real MeRIP-seq data from human lymphoblastoid cell lines, we have uncovered the complex regulatory pattern of predicted m6A sites and their unique enrichment pathway of the constructed co-methylation modules. m6Aexpress-enet proves itself as a powerful tool to enable biologists to discover the mechanism of m6A regulatory gene expression. Furthermore, the source code and the step-by-step implementation of m6Aexpress-enet is freely accessed at https://github.com/tengzhangs/m6Aexpress-enet.

Hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

BACKGROUND: Postoperative Cognitive Dysfunction (POCD) has attracted increased attention, but its precise mechanism remains to be explored. This study aimed to figure out whether HDAC6 could regulate NLRP3-induced pyroptosis by modulating the functions of HSP70 and HSP90 in microglia to participate in postoperative cognitive dysfunction in aged mice. METHODS: Animal models of postoperative cognitive dysfunction in aged mice were established by splenectomy under sevoflurane anesthesia. Morris water maze was used to examine the cognitive function and motor ability. Sixteen-months-old C57BL/6 male mice were randomly divided into six groups: control group (C group), sham surgery group (SA group), splenectomy group (S group), splenectomy + HDAC6 inhibitor ACY-1215 group (ACY group), splenectomy + HDAC6 inhibitor ACY-1215 + HSP70 inhibitor Apoptozole group (AP group), splenectomy + solvent control group (SC group). The serum and hippocampus of mice were taken after mice were executed. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, cleaved-Caspase-1 (P20), IL-1ß were detected by western blotting. Serum IL-1ß, IL-6 and S100ß were measured using ELISA assay, and cell localization of HDAC6 was detected by immunofluorescence. In vitro experiments, BV2 cells were used to validate whether this mechanism worked in microglia. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, P20, IL-1ß were detected by western blotting and the content of IL-1ß in the supernatant was measured using ELISA assay. The degree of acetylation of HSP90, the interaction of HSP70, HSP90 and NLRP3 were analyzed by coimmunoprecipitation assay. RESULTS: Splenectomy under sevoflurane anesthesia in aged mice could prolong the escape latency, reduce the number of crossing platforms, increase the expression of HDAC6 and activate the NLRP3 inflammasome to induce pyroptosis in hippocampus microglia. Using ACY-1215 could reduce the activation of NLRP3 inflammasome, the pyroptosis of microglia and the degree of spatial memory impairment. Apoptozole could inhibit the binding of HSP70 to NLRP3, reduce the degradation of NLRP3 and reverse the protective effect of HDAC6 inhibitors. The results acquired in vitro experiments closely resembled those in vivo, LPS stimulation led to the pyroptosis of BV2 microglia cells and the release of IL-1ß due to the activation of the NLRP3 inflammasome, ACY-1215 showed the anti-inflammatory effect and Apoptozole exerted the opposite effect. CONCLUSIONS: Our findings suggest that hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

A new species of the genus Achalinus (Squamata, Xenodermatidae) from southwest Hunan Province, China.

A new species of xenodermid snake, Achalinusnanshanensis H. Li, L.-Q. Zhu, Z.-Q. Zhang & X.-Y. Mo, sp. nov., is described based on three specimens collected from Nanshan National Park and Tongdao County of southwest Hunan Province. This new species is genetically distinct amongst its congeners with the mitochondrial COI uncorrected p-distance ranging from 4.4% (in A.yangdatongi) to 17.7% (in A.meiguensis). In addition, this new species can be distinguished from its congeners by a combination of the following morphological characters: (1) dorsal scales with 23 or 25 rows throughout and strongly keeled; (2) tail relatively longer so that TaL/ToL = 0.215-0.248; (3) length of suture between internasals significantly longer than that between prefrontals, LSBI/LSBP = 1.66-1.84; (4) single loreal scale present; (5) SPL 6 in number, with the fourth and fifth contacting eye; (6) IFL 6 in number, with the first three touching the first pair of chin shields; (7) TMP is 2-2-4/2-2(3)-4, with the anterior pair elongated and in contact with the eye; (8) ventrals 2 + 147-158; (9) subcaudals 64-77, unpaired; (10) dorsal body brownish black, with a bright yellow neck collar extending to the head and abdomen in the occipital region. The recognition of the new species increases the number of described Achalinus species to 28, of which 21 are found in China.

Competitive Formation Mechanism for Bidentate Passivation of Halogen Vacancies in Perovskite Based on 6-Chloropurine.

For metal halide perovskite solar cells, bidentate passivation (BP) is highly effective, but currently, only passivation sites rather than molecular environments are being considered. Here, the authors report an effective approach for high-performance fully printable mesoscopic perovskite solar cells (FP-PSCs) through the BP strategy using the multidentate molecule 6-chloropurine (6-CP). By utilizing density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR) characterizations, the competition mechanism is identified of BP between the chlorine atom and neighboring nitrogen atom of the imidazole and pyrimidine rings. Through BP between the chlorine atom and adjacent nitrogen atom in imidazole, the power conversion efficiency (PCE) of the pristine samples is significantly enhanced from 16.25% to 17.63% with 6-CP. The formation of BP enhances interfacial hole selectivity and charge transfer, and suppresses nonradiative recombination, improving device stability under high humidity conditions. The competition mechanism of BP between two aromatic cycles provides a path for designing molecular passivants and selecting passivation pathways to approach theoretical limits.

The TAE score predicts prognosis of unresectable HCC patients treated with TACE plus lenvatinib with PD-1 inhibitors.

BACKGROUND AND AIMS: Transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) exhibits promising efficacy for unresectable hepatocellular carcinoma (uHCC). We aimed to evaluate the prognosis of patients with uHCC who received triple therapy and develop a prognostic scoring model to identify patients who benefit the most from triple therapy. METHODS: A total of 246 patients with uHCC who received triple therapy at eight centers were included and assigned to the training and validation cohorts. Prognosis was evaluated by the Kaplan-Meier curves. The prognostic model was developed by utilizing predictors of overall survival (OS), which were identified through the Cox proportional hazards model. RESULTS: In the training cohort, the 3-year OS was 52.0%, with a corresponding progression-free survival (PFS) of 30.6%. The median PFS was 13.2 months [95% confidence interval, 9.7-16.7]. Three variables (total bilirubin ≥ 17 µmol/L, alpha-fetoprotein ≥ 400 ng/mL, and extrahepatic metastasis) were predictors of poor survival and were used for developing a prognostic model (TAE score). The 2-year OS rates in the favorable (0 points), intermediate (1 point), and dismal groups (2-3 points) were 96.9%, 61.4%, and 11.4%, respectively (p < 0.001). The PFS was also stratified according to the TAE score. These findings were confirmed in an external validation cohort. CONCLUSIONS: Triple therapy showed encouraging clinical outcomes, and the TAE score aids in identifying patients who would benefit the most from triple therapy.

LncRNA pol-lnc78 as a ceRNA regulates antibacterial responses via suppression of pol-miR-n199-3p-mediated SARM down-regulation in Paralichthys olivaceus.

Long non-coding RNAs (lncRNAs) function as key modulators in mammalian immunity, particularly due to their involvement in lncRNA-mediated competitive endogenous RNA (ceRNA) crosstalk. Despite their recognized significance in mammals, research on lncRNAs in lower vertebrates remains limited. In the present study, we characterized the first immune-related lncRNA (pol-lnc78) in the teleost Japanese flounder ( Paralichthys olivaceus). Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein (SARM), the fifth discovered member of the Toll/interleukin 1 (IL-1) receptor (TIR) adaptor family. This ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor (TLR) signaling pathway. Specifically, SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1ß and tumor necrosis factor-α (TNF-α). Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3' untranslated region (UTR), thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial dissemination. Furthermore, pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM expression. During infection, the negative regulators pol-lnc78 and SARM were significantly down-regulated, while pol-miR-n199-3p was significantly up-regulated, thus favoring host antibacterial defense. These findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.

Clinical Complete Response After Conversion Therapy for Unresectable Hepatocellular Carcinoma: Is Salvage Hepatectomy Necessary?

Background: This study aimed to determine whether salvage hepatectomy offers prognostic advantages for unresectable hepatocellular carcinoma (uHCC) patients with clinical complete response (cCR) after conversion therapy. Methods: A total of 74 consecutive uHCC patients with cCR after conversion therapy at seven major cancer centers in China between October 2018 and December 2021 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Disease-free survival (DFS) and overall survival (OS) rates were compared between the surgical group and the non-surgical group. Results: Before PSM, 45 patients received salvage hepatectomy, and 29 patients received nonsurgical treatment. The 1-, 2-, and 3-year DFS rates were 77.8%, 61.5%, and 61.5% in the surgical group and 81.2%, 60.9%, and 60.9% in the non-surgical group, respectively. The 1-, 2-, and 3-year OS rates were 92.9%, 92.9%, and 69.7% in the surgical group and 100%, 70%, and 70% in the non-surgical group, respectively. There were no statistical differences in DFS and OS between groups [hazard ratio (HR)=0.715, 95% confidence interval (CI): 0.250-2.043, p=0.531; HR=0.980, 95% CI: 0.177-5.418, p=0.982, respectively]. After PSM, 26 pairs of patents were selected; there remained no significant differences in DFS and OS between these two groups (HR=1.547, 95% CI: 0.512-4.669, p=0.439; HR=1.024, 95% CI: 0.168-6.242, p=0.979, respectively). Conclusion: Through the study, it tend to show that salvage hepatectomy may be not essential for uHCC patients with cCR, especially for patients with a high risk of surgical complications. Prospective trials with long term follow-up are warranted to evaluate this treatment option.

Diagnosis of Alzheimer's disease by joining dual attention CNN and MLP based on structural MRIs, clinical and genetic data.

Alzheimer's disease (AD) is an irreversible central nervous degenerative disease, while mild cognitive impairment (MCI) is a precursor state of AD. Accurate early diagnosis of AD is conducive to the prevention and early intervention treatment of AD. Although some computational methods have been developed for AD diagnosis, most employ only neuroimaging, ignoring other data (e.g., genetic, clinical) that may have potential disease information. In addition, the results of some methods lack interpretability. In this work, we proposed a novel method (called DANMLP) of joining dual attention convolutional neural network (CNN) and multilayer perceptron (MLP) for computer-aided AD diagnosis by integrating multi-modality data of the structural magnetic resonance imaging (sMRI), clinical data (i.e., demographics, neuropsychology), and APOE genetic data. Our DANMLP consists of four primary components: (1) the Patch-CNN for extracting the image characteristics from each local patch, (2) the position self-attention block for capturing the dependencies between features within a patch, (3) the channel self-attention block for capturing dependencies of inter-patch features, (4) two MLP networks for extracting the clinical features and outputting the AD classification results, respectively. Compared with other state-of-the-art methods in the 5CV test, DANMLP achieves 93% and 82.4% classification accuracy for the AD vs. MCI and MCI vs. NC tasks on the ADNI database, which is 0.2%∼15.2% and 3.4%∼26.8% higher than that of other five methods, respectively. The individualized visualization of focal areas can also help clinicians in the early diagnosis of AD. These results indicate that DANMLP can be effectively used for diagnosing AD and MCI patients.

A novel cross-layer dual encoding-shared decoding network framework with spatial self-attention mechanism for hippocampus segmentation.

Accurate segmentation of the hippocampus from the brain magnetic resonance images (MRIs) is a crucial task in the neuroimaging research, since its structural integrity is strongly related to several neurodegenerative disorders, such as Alzheimer's disease (AD). Automatic segmentation of the hippocampus structures is challenging due to the small volume, complex shape, low contrast and discontinuous boundaries of hippocampus. Although some methods have been developed for the hippocampus segmentation, most of them paid too much attention to the hippocampus shape and volume instead of considering the spatial information. Additionally, the extracted features are independent of each other, ignoring the correlation between the global and local information. In view of this, here we proposed a novel cross-layer dual Encoding-Shared Decoding network framework with Spatial self-Attention mechanism (called ESDSA) for hippocampus segmentation in human brains. Considering that the hippocampus is a relatively small part in MRI, we introduced the spatial self-attention mechanism in ESDSA to capture the spatial information of hippocampus for improving the segmentation accuracy. We also designed a cross-layer dual encoding-shared decoding network to effectively extract the global information of MRIs and the spatial information of hippocampus. The spatial features of hippocampus and the features extracted from the MRIs were combined to realize the hippocampus segmentation. Results on the baseline T1-weighted structural MRI data show that the performance of our ESDSA is superior to other state-of-the-art methods, and the dice similarity coefficient of ESDSA achieves 89.37%. In addition, the dice similarity coefficient of the Spatial Self-Attention mechanism (SSA) strategy and the dual Encoding-Shared Decoding (ESD) strategy is 9.47%, 5.35% higher than that of the baseline U-net, respectively, indicating that the strategies of SSA and ESD can effectively enhance the segmentation accuracy of human brain hippocampus.

Engineering Phenothiazine-Based Functional Mimics of Host Defense Peptides as New Agrochemical Candidates: Design, Synthesis, and Antibacterial Evaluation.

In the protracted "arms race" between host and plant pathogenic bacteria, host organisms have evolved powerful weapons known as host defense peptides (HDPs). However, natural HDPs are not suitable for large-scale applications; therefore, researchers have chosen to develop bespoke small-molecule functional mimics. Phenothiazine derivatives were developed as functional HDPs mimics, owing to their broad biological activity and high lipophilicity. The phenothiazine analogues designed in this study exhibited excellent in vitro bioactivity against the three Gram-negative bacteria Xanthomonas oryzae pv oryzae, Xanthomonas axonopodis pv citri, and Pseudomonas syringae pv actinidiae, with optimal EC50 values of 0.80, 0.31, and 1.91 µg/mL, respectively. Preliminary evidence suggests that compound C2 may act on bacterial cell membranes and interact with bacterial Deoxyribonucleic acid in the groove binding mode. In vivo trials showed that compound C2 was highly effective against rice leaf blight (51.97-56.69%), with activity superior to those of bismerthiazol (40.7-43.4%) and thiodiazole copper (30.2-37.1%). Our study provides strong evidence to support the development of phenothiazine derivatives into pesticide candidates.

The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases.

Cerebral ischemia, a leading cause of disability and mortality worldwide, triggers a cascade of molecular and cellular pathologies linked to several central nervous system (CNS) disorders. These disorders primarily encompass ischemic stroke, Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and other CNS conditions. Despite substantial progress in understanding and treating the underlying pathological processes in various neurological diseases, there is still a notable absence of effective therapeutic approaches aimed specifically at mitigating the damage caused by these illnesses. Remarkably, ischemia causes severe damage to cells in ischemia-associated CNS diseases. Cerebral ischemia initiates oxygen and glucose deprivation, which subsequently promotes mitochondrial dysfunction, including mitochondrial permeability transition pore (MPTP) opening, mitophagy dysfunction, and excessive mitochondrial fission, triggering various forms of cell death such as autophagy, apoptosis, as well as ferroptosis. Ferroptosis, a novel type of regulated cell death (RCD), is characterized by iron-dependent accumulation of lethal reactive oxygen species (ROS) and lipid peroxidation. Mitochondrial dysfunction and ferroptosis both play critical roles in the pathogenic progression of ischemia-associated CNS diseases. In recent years, growing evidence has indicated that mitochondrial dysfunction interplays with ferroptosis to aggravate cerebral ischemia injury. However, the potential connections between mitochondrial dysfunction and ferroptosis in cerebral ischemia have not yet been clarified. Thus, we analyzed the underlying mechanism between mitochondrial dysfunction and ferroptosis in ischemia-associated CNS diseases. We also discovered that GSH depletion and GPX4 inactivation cause lipoxygenase activation and calcium influx following cerebral ischemia injury, resulting in MPTP opening and mitochondrial dysfunction. Additionally, dysfunction in mitochondrial electron transport and an imbalanced fusion-to-fission ratio can lead to the accumulation of ROS and iron overload, which further contribute to the occurrence of ferroptosis. This creates a vicious cycle that continuously worsens cerebral ischemia injury. In this study, our focus is on exploring the interplay between mitochondrial dysfunction and ferroptosis, which may offer new insights into potential therapeutic approaches for the treatment of ischemia-associated CNS diseases.

Dehydroabietane-type bifunctional organocatalysts in asymmetric synthesis: recent progress.

Dehydroabietane-type bifunctional organocatalysts derived from rosane-type diterpenes of dehydroabietic acid (DHAA) and dehydroabietylamine (DA) have been utilized in a wide variety of highly enantioselective reactions. Since one well-documented review exclusively reported on the development of terpene-derived bifunctional thioureas in asymmetric organocatalysis in 2013, fragmentary progress on the dehydroabietane-type bifunctional thioureas and squaramides has been mentioned in other reviews. In this mini-review, we systematically analyze and reorganize the published literature on dehydroabietane-type bifunctional organocatalysts in the recent decade according to the type of catalysts. Our aim is for this review to provide helpful research information and serve as a foundation for further design and application of rosin-based organocatalysts.

PhenoDriver: interpretable framework for studying personalized phenotype-associated driver genes in breast cancer.

Identifying personalized cancer driver genes and further revealing their oncogenic mechanisms is critical for understanding the mechanisms of cell transformation and aiding clinical diagnosis. Almost all existing methods primarily focus on identifying driver genes at the cohort or individual level but fail to further uncover their underlying oncogenic mechanisms. To fill this gap, we present an interpretable framework, PhenoDriver, to identify personalized cancer driver genes, elucidate their roles in cancer development and uncover the association between driver genes and clinical phenotypic alterations. By analyzing 988 breast cancer patients, we demonstrate the outstanding performance of PhenoDriver in identifying breast cancer driver genes at the cohort level compared to other state-of-the-art methods. Otherwise, our PhenoDriver can also effectively identify driver genes with both recurrent and rare mutations in individual patients. We further explore and reveal the oncogenic mechanisms of some known and unknown breast cancer driver genes (e.g. TP53, MAP3K1, HTT, etc.) identified by PhenoDriver, and construct their subnetworks for regulating clinical abnormal phenotypes. Notably, most of our findings are consistent with existing biological knowledge. Based on the personalized driver profiles, we discover two existing and one unreported breast cancer subtypes and uncover their molecular mechanisms. These results intensify our understanding for breast cancer mechanisms, guide therapeutic decisions and assist in the development of targeted anticancer therapies.

Discovery of novel phenothiazine derivatives as new agrochemical alternatives for treating plant viral diseases.

BACKGROUND: Plant viral diseases, namely 'plant cancer', are extremely difficult to control. Even worse, few antiviral agents can effectively control and totally block viral infection. There is an urgent need to explore and discover novel agrochemicals with high activity and a unique mode of action to manage these refractory diseases. RESULTS: Forty-one new phenothiazine derivatives were prepared and their inhibitory activity against tobacco mosaic virus (TMV) was assessed. Compound A8 had the highest protective activity against TMV, with a half-maximal effective concentration (EC50 ) of 115.67 µg/mL, which was significantly better than that of the positive controls ningnanmycin (271.28 µg/mL) and ribavirin (557.47 µg/mL). Biochemical assays demonstrated that compound A8 could inhibit TMV replication by disrupting TMV self-assembly, but also enabled the tobacco plant to enhance its defense potency by increasing the activities of various defense enzymes. CONCLUSION: In this study, novel phenothiazine derivatives were elaborately fabricated and showed remarkable anti-TMV behavior that possessed the dual-action mechanisms of inhibiting TMV assembly and invoking the defense responses of tobacco plants. Moreover, new agrochemical alternatives based on phenothiazine were assessed for their antiviral activities and showed extended agricultural application. © 2023 Society of Chemical Industry.

Effects of short-term extreme temperature treatment on the development and reproductive capacity of Encarsia formosa.

Encarsia formosa is a natural enemy of the invasive pest Bemisia tabaci and is known to be a dominant parasitic. The frequency and magnitude of climate extremes, particularly temperature extremes, have increased, which has put insect populations at risk. However, the effects of temperature extremes on E. formosa are not well understood. To examine the impact of short-term extreme temperature exposure on the development and reproduction of E. formosa, eggs, larvae, pupae, and adults were exposed to high/low temperature treatments (HLT25, HLT50, LLT25, and LLT50). Our findings indicate that the pupal stage of E. formosa exhibited the strongest tolerance to both heat and cold, while adults exhibited a weaker tolerance. The shortest egg-to-adult development period of 12.65 days was observed in E. formosa exposed to HLT50 treatment during the egg-larval stage. The parasitism peak of the adult stage was delayed by 1-6 days after exposure to extreme temperatures during the egg-larval stage. Conversely, the parasitism peak was advanced by 1-3 days after exposure to extreme temperatures during the pupal and adult stages. The eclosion rate, total parasitism, eclosion rate of the F1 generation, and adult longevity of the F1 generation were lower in the treatment groups than in the control groups. The F1 generation's development period was prolonged to 15.49 and 15.19 days after exposure to HLT25 and HLT50 treatments, respectively, during the egg-larval stage. The F1 generation's development period was shortened to 13.33 days after exposure to LLT50 treatment during the pupal stage. Male individuals appeared in the F1 generation after exposure to HLT50 treatment during the pupal stage, with females accounting for only 56.38%. Our results demonstrate that short-term exposure to extreme temperatures has detrimental effects on the growth and reproduction of E. formosa. In field biocontrol against E. formosa, the release of E. formosa should be avoided as much as possible when the ambient temperature is higher than 35°C or lower than 0°C. During extreme temperature conditions, timely supplementation and release of E. formosa population, along with ventilation and cooling in greenhouse facilities during summer, are necessary for better pest control efficacy.

Taxonomy and Phylogenetic Relationships of Clavulinopsis (Clavariaceae, Agaricales): Description of Six New Species and One Newly Recorded Species from China.

Specimens of Clavulinopsis (Clavariaceae, Agaricales) collected in China were studied using morphological and molecular methods. Six species-C. aspersa, C. bicolor, C. bispora, C. erubescens, C. incarnata, and C. tropicalis-are described as new to science, and C. trigonospora is a newly recorded species in China. Phylogenetic analysis was conducted based on a combined dataset of internal transcribed spacer and nuclear ribosomal RNA large subunit sequences. The phylogenetic reconstruction revealed that the six new species each formed an independent lineage, and the samples of C. trigonospora from China were nested with accessions of C. trigonospora collected from Italy. The morphology of the seven Chinese species is described in detail, and is illustrated with line drawings and photographs. A key to the known Clavulinopsis species in China is provided.

Radiomics model based on intravoxel incoherent motion and diffusion kurtosis imaging for predicting histopathological grade and Ki-67 expression level of soft tissue sarcomas.

BACKGROUND: Accurate identification of the histopathological grade and the Ki-67 expression level is important in clinical cases of soft tissue sarcomas (STSs). PURPOSE: To explore the feasibility of a radiomics model based on intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and diffusion kurtosis imaging (DKI) MRI parameter maps in predicting the histopathological grade and Ki-67 expression level of STSs. MATERIAL AND METHODS: In total, 42 patients diagnosed with STSs between May 2018 and January 2020 were selected. The MADC software in Functool of GE ADW 4.7 workstation was used to obtain standard apparent diffusion coefficient (ADC), D, D*, f, mean diffusivity, and mean kurtosis (MK). The histopathological grade and Ki-67 expression level of STSs were identified. The radiomics features of IVIM and DKI parameter maps were used as the dataset. The area under the receiver operating characteristic curve (AUC) and F1-score were calculated. RESULTS: D-SVM achieved the best diagnostic performance for histopathological grade. The AUC in the validation cohort was 0.88 (sensitivity: 0.75 [low level] and 0.83 [high level]; specificity: 0.83 [low level] and 0.75 [high level]; F1-score: 0.75 [low level] and 0.83 [high level]). MK-SVM achieved the best diagnostic performance for Ki-67 expression level. The AUC in the validation cohort was 0.83 (sensitivity: 0.83 [low level] and 0.50 [high level; specificity: 0.50 [low level] and 0.83 [high level]; F1-score: 0.77 [low level] and 0.57 [high level]). CONCLUSION: The proposed radiomics classifier could predict the pathological grade of STSs and the Ki-67 expression level in STSs.

Exploiting Natural Maltol for Synthesis of Novel Hydroxypyridone Derivatives as Promising Anti-Virulence Agents in Bactericides Discovery.

Anti-infection strategies based on suppression of bacterial virulence factors represent a crucial direction for the development of new antibacterial agents to address the resistance triggered by traditional drugs'/pesticides' bactericidal activity. To identify and obtain more effective and diverse molecules targeting virulence, we prepared a series of 3-hydroxy-2-methyl-1-pyridin-4-(1H)-one derivatives and evaluated their antibacterial behaviors. Compound B6 exhibited the highest bioactivity, with half-maximal effective concentration (EC50) values ranging fro9m 10.03 to 30.16 µg mL-1 against three plant pathogenic bacteria. The antibacterial mechanism showed that it could considerably reduce various virulence factors (such as extracellular enzymes, biofilm, and T3SS effectors) and inhibit the expression of virulence factor-related genes. In addition, the control efficiency of compound B6 against rice bacterial leaf blight at 200 µg mL-1 was 46.15-49.15%, and their control efficiency was improved by approximately 12% after the addition of pesticide additives. Thus, a new class of bactericidal candidates targeting bacterial virulence factors was developed for controlling plant bacterial diseases.

ncRPI-LGAT: Prediction of ncRNA-protein interactions with line graph attention network framework.

Identification of ncRNA-protein interactions (ncRPIs) through wet experiments is still time-consuming and highly-costly. Although several computational approaches have been developed to predict ncRPIs using the structure and sequence information of ncRNAs and proteins, the prediction accuracy needs to be improved, and the results lack interpretability. In this work, we proposed a novel computational method (called ncRPI-LGAT) to predict the ncRNA-Protein Interactions by transforming the link prediction (i.e., subgraph classification) task into a node classification task in the line network, and introducing a Line Graph ATtention network framework. ncRPI-LGAT first extracts the ncRNA/protein attributes using node2vec, and then generates the local enclosing subgraph of a target ncRNA-protein pair with SEAL. Because using the pooling operations in local enclosing subgraphs to learn a fixed-size feature vector for representing ncRNAs/proteins will cause the information loss, ncRPI-LGAT converts the local enclosing subgraphs into their corresponding line graphs, in which the node corresponds to the edge (i.e., ncRNA-protein pair) of the local enclosing subgraphs. Then, the attention mechanism-based graph neural network GATv2 is used on these line graphs to efficiently learn the embedding features of the target nodes (i.e., ncRNA-protein pairs) by focusing on learning the significance of one ncRNA-protein pair to another ncRNA-protein pair. These embedding features of one ncRNA-protein pair obtained from multi-head attention are concatenated in series and then fed them into a fully connected network to predict ncRPIs. Compared with other state-of-the-art methods in the 5CV test, ncRPI-LGAT shows superior performance on three benchmark datasets, demonstrating the effectiveness of our ncRPI-LGAT method in predicting ncRNA-protein interactions.