SurfPro-NN: A 3D point cloud neural network for the scoring of protein-protein docking models based on surfaces features and protein language models.

Protein-protein interactions (PPI) play a crucial role in numerous key biological processes, and the structure of protein complexes provides valuable clues for in-depth exploration of molecular-level biological processes. Protein-protein docking technology is widely used to simulate the spatial structure of proteins. However, there are still challenges in selecting candidate decoys that closely resemble the native structure from protein-protein docking simulations. In this study, we introduce a docking evaluation method based on three-dimensional point cloud neural networks named SurfPro-NN, which represents protein structures as point clouds and learns interaction information from protein interfaces by applying a point cloud neural network. With the continuous advancement of deep learning in the field of biology, a series of knowledge-rich pre-trained models have emerged. We incorporate protein surface representation models and language models into our approach, greatly enhancing feature representation capabilities and achieving superior performance in protein docking model scoring tasks. Through comprehensive testing on public datasets, we find that our method outperforms state-of-the-art deep learning approaches in protein-protein docking model scoring. Not only does it significantly improve performance, but it also greatly accelerates training speed. This study demonstrates the potential of our approach in addressing protein interaction assessment problems, providing strong support for future research and applications in the field of biology.

CT-based intratumoral and peritumoral deep transfer learning features prediction of lymph node metastasis in non-small cell lung cancer.

BACKGROUND: The main metastatic route for lung cancer is lymph node metastasis, and studies have shown that non-small cell lung cancer (NSCLC) has a high risk of lymph node infiltration. OBJECTIVE: This study aimed to compare the performance of handcrafted radiomics (HR) features and deep transfer learning (DTL) features in Computed Tomography (CT) of intratumoral and peritumoral regions in predicting the metastatic status of NSCLC lymph nodes in different machine learning classifier models. METHODS: We retrospectively collected data of 199 patients with pathologically confirmed NSCLC. All patients were divided into training (n = 159) and validation (n = 40) cohorts, respectively. The best HR and DTL features in the intratumoral and peritumoral regions were extracted and selected, respectively. Support Vector Machine (SVM), k-Nearest Neighbors (KNN), Light Gradient Boosting Machine (Light GBM), Multilayer Perceptron (MLP), and Logistic Regression (LR) models were constructed, and the performance of the models was evaluated. RESULTS: Among the five models in the training and validation cohorts, the LR classifier model performed best in terms of HR and DTL features. The AUCs of the training cohort were 0.841 (95% CI: 0.776-0.907) and 0.955 (95% CI: 0.926-0.983), and the AUCs of the validation cohort were 0.812 (95% CI: 0.677-0.948) and 0.893 (95% CI: 0.795-0.991), respectively. The DTL signature was superior to the handcrafted radiomics signature. CONCLUSIONS: Compared with the radiomics signature, the DTL signature constructed based on intratumoral and peritumoral areas in CT can better predict NSCLC lymph node metastasis.

The classification of benign and malignant lung nodules based on CT radiomics: a systematic review, quality score assessment, and meta-analysis.

Radiomics methods are increasingly used to identify benign and malignant lung nodules, and early monitoring is essential in prognosis and treatment strategy formulation. To evaluate the diagnostic performance of computed tomography (CT)-based radiomics for distinguishing between benign and malignant lung nodules by performing a meta-analysis. Between January 2000 and December 2021, we searched the PubMed and Embase electronic databases for studies in English. Studies were included if they demonstrated the sensitivity and specificity of CT-based radiomics for diagnosing benign and malignant lung nodules. The studies were evaluated using the QUADAS-2 and radiomics quality scores (RQS). The inhomogeneity of the data and publishing bias were also evaluated. Some subgroup analyses were performed to investigate the impact of diagnostic efficiency. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Guidelines were followed for this meta-analysis. A total of 20 studies involving 3793 patients were included. The combined sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating characteristic curve based on CT radiomics diagnosis of benign and malignant lung nodules were 0.81, 0.86, 27.00, and 0.91, respectively. Deek's funnel plot asymmetry test confirmed no significant publication bias in all studies. Fagan nomograms showed a 40% increase in post-test probability among pretest-positive patients. Current evidence shows that CT-based radiomics has high accuracy in the diagnosis of benign and malignant lung nodules.

CT-based radiomics models may predict the early efficacy of microwave ablation in malignant lung tumors.

PURPOSE: To establish and validate radiomics models for predicting the early efficacy (less than 3 months) of microwave ablation (MWA) in malignant lung tumors. METHODS: The study enrolled 130 malignant lung tumor patients (72 in the training cohort, 32 in the testing cohort, and 26 in the validation cohort) treated with MWA. Post-operation CT images were analyzed. To evaluate the therapeutic effect of ablation, three models were constructed by least absolute shrinkage and selection operator and logistic regression: the tumoral radiomics (T-RO), peritumoral radiomics (P-RO), and tumoral-peritumoral radiomics (TP-RO) models. Univariate and multivariate analyses were performed to identify clinical variables and radiomics features associated with early efficacy, which were incorporated into the combined radiomics (C-RO) model. The performance of the C-RO model was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis (DCA). The C-RO model was used to derive the best cutoff value of ROC and to distinguish the high-risk group (Nomo-score of C-RO model below than cutoff value) from the low-risk group (Nomo-score of C-RO model higher than cutoff value) for survival analysis of patients. RESULTS: Four radiomics features were selected from the region of interest of tumoral and peritumoral CT images, which showed good performance for evaluating prognosis and early efficacy in three cohorts. The C-RO model had the highest AUC value in all models, and the C-RO model was better than the P-RO model (AUC in training, 0.896 vs. 0.740; p = 0.036). The DCA confirmed the clinical benefit of the C-RO model. Survival analysis revealed that in the C-RO model, the low-risk group defined by best cutoff value had significantly better progression-free survival than the high-risk group (p<0.05). CONCLUSIONS: CT-based radiomics models in malignant lung tumor patients after MWA could be useful for individualized risk classification and treatment.

Subcutaneous phaeohyphomycosis caused by plant pathogenic Corynespora cassiicola: A case report.

Corynespora cassiicola is a common plant pathogen responsible for leaf-spotting diseases in the tropical and subtropical areas. C. cassiicola seldom causes human infections. Here we describe a case of subcutaneous phaeohyphomycosis caused by C. cassiicola in a 76-year-old Chinese man, who presented to our hospital with a purulent discharge and painful sensation on his right leg. Skin biopsy revealed an abscess, and culture confirmed C. cassiicola to be the causative agent. The result was further identified by sequence analysis of the internal transcribed spacer region. The patient was successfully treated with systemic voriconazole and wound debridement: the lesion disappeared after 20 days.

The interplay between small vessel disease and Parkinson disease pathology: A longitudinal study.

BACKGROUND: Cerebral small vessel disease (SVD) related brain changes have been found associated with various clinical symptoms of Parkinson disease (PD). On the other hand, PD pathology and treatment may also accelerate SVD progression. OBJECTIVE: The aim of this study is to explore the interplay between SVD and PD pathology using longitudinal dataset. METHODS: We screened 66 healthy controls (HCs) and 114 patients from the Parkinson Progression Markers Initiative (PPMI) database. The peak width of skeletonized mean diffusivity (PSMD) was quantified from diffusion tensor images to reflect vascular pathologies at baseline and 24 months follow-up, and dopamine transporter (DAT) imaging data was used to represent the extent of dopaminergic neuronal degeneration at the same point time. We compared the PSMD between PD patients and HCs, and analyzed whether PSMD and DAT availability could predict each other's progression using multiple regression analyses in PD patients. RESULTS: PSMD at baseline had no significant difference between the HCs and patients with PD (P = 0.169). Higher baseline PSMD was associated with less DAT reduction in the caudate (ß = 0.216, P = 0.029), but not the putamen (ß = 0.058, P = 0.552) in PD patients. Baseline caudate and putamen DAT availability had no significant association with PSMD progression (ß = -0.006, P = 0.950; ß = 0.017, P = 0.860, respectively). CONCLUSIONS: Mild SVD might slow down PD pathology progression, while the effect of PD pathology on the progression of SVD was not significant.

Neural Network Optimal Routing Algorithm Based on Genetic Ant Colony in IPv6 Environment.

The traditional IPv6 routing algorithm has problems such as network congestion, excessive energy consumption of nodes, and shortening the life cycle of the network. In response to this phenomenon, we proposed a routing optimization algorithm based on genetic ant colony in IPv6 environment. The algorithm analyzes and studies the genetic algorithm and the ant colony algorithm systematically. We use neural network to build the initial model and combine the constraints of QoS routing. We effectively integrate the genetic algorithm and ant colony algorithm that maximize their respective advantages and apply them to the IPv6 network. At the same time, in order to avoid the accumulation of a lot of pheromones by the ant colony algorithm in the later stage of the network, we have introduced an anticongestion reward and punishment mechanism. By comparing the search path with the optimal path, rewards and punishments are based on whether the network path is smooth or not. Finally, it is judged whether the result meets the condition, and the optimal solution obtained is passed to the BP neural network for training; otherwise, iterative iterations are required until the optimal solution is satisfied. The experimental results show that the algorithm can effectively adapt to the IPv6 routing requirements and can effectively solve the user's needs for network service quality, network performance, and other aspects.

Preliminary Evaluation of Rapid Visual Identification of Burkholderia pseudomallei Using a Newly Developed Lateral Flow Strip-Based Recombinase Polymerase Amplification (LF-RPA) System.

Burkholderia pseudomallei is an important infectious disease pathogen that can cause melioidosis. Melioidosis is mainly prevalent in Thailand, northern Australia and southern China and has become a global public health problem. Early identification of B. pseudomallei is of great significance for the diagnosis and prognosis of melioidosis. In this study, a simple and visual device combined with lateral flow strip-based recombinase polymerase amplification (LF-RPA) was developed, and the utility of the LF-RPA assay for identifying B. pseudomallei was evaluated. In order to screen out the optimal primer probe, a total of 16 pairs of specific primers targeting the orf2 gene of B. pseudomallei type III secretion system (T3SS) cluster genes were designed for screening, and F1/R3 was selected as an optimal set of primers for the identification of B. pseudomallei, and parameters for LF-RPA were optimized. The LF-RPA can be amplified at 30-45°C and complete the entire reaction in 5-30 min. This reaction does not cross-amplify the DNA of other non-B. pseudomallei species. The limit of detection (LOD) of this assay for B. pseudomallei genomic DNA was as low as 30 femtograms (fg), which was comparable to the results of real-time PCR. Moreover, 21 clinical B. pseudomallei isolates identified by 16S rRNA gene sequencing were retrospectively confirmed by the newly developed LF-RPA system. Our results showed that the newly developed LF-RPA system has a simple and short time of operation and has good application prospect in the identification of B. pseudomallei.

Regioselective Radical Reaction of Monometallofullerene Y@C2v(9)-C82 With N-arylbenzamidine Mediated by Silver Carbonate.

A novel radical reaction of monometallofullerene Y@C2v(9)-C82 with N-arylbezamidine (1) is successfully conducted through catalysis with silver carbonate. The high-performance liquid chromatographic and mass spectrum results demonstrate that the reaction is highly regioselective to afford only one monoadduct (2) with an imidazoline group added on C82 cage, and computations through density functional theory reveal the addition group is attached to a specific [5, 6]-bond (C20-C76) near the Y atom. Furthermore, the analysis of prymidalization angle of the carbon atoms demonstrates the geometry of carbon cage is in favor of the regioselective formation of isomer (20, 76).

Complete mitochondrial genome of a hydrocarbon-producing green alga Botryococcus braunii strain Showa.

Complete mitochondrial genome of Botryococcus braunii strain Showa was assembled and annotated. It contains 31 protein-coding genes, 23 tRNA genes and 3 rRNA (23S, 16S, 5S rRNA) genes. The 31 protein-coding genes include 5 atp genes, 3 cox genes, 9 nad genes, 12 ribosomal protein genes, cob and tatC genes. The presence of extra non-coding regions makes it currently the largest mitochondrial genome in Trebouxiophyceae. Phylogenetic analysis showed Botryococcus braunii strain Showa clustered into Trebouxiophyceae clade and had close genetic relationship with algae Coccomyxa sp. C-169.

The genome-wide identification of mitogen-activated protein kinase kinase (MKK) genes in Yesso scallop Patinopecten yessoensis and their expression responses to bacteria challenges.

Mitogen-activated protein kinase kinases (MKK) are the essential components of the evolutionarily conserved MAPK signaling cascade, which regulates a variety of cellular activities and innate immune responses. Although MKK genes have been extensively studied in various vertebrate and invertebrate species, they have not been systematically characterized in bivalves. In this study, we identified and characterized five MKK genes (PyMKK1/2, PyMKK4, PyMKK5, PyMKK3/6 and PyMKK7) in the Yesso scallop (Patinopecten yessoensis). Phylogenetic and protein structural analyses were conducted to determine their identities and evolutionary relationships. To gain insights into the possible roles of MKK genes during scallop innate immune responses, quantitative real-time PCR (qRT-PCR) was used to investigate their expression profiles during different developmental stages in samples taken from healthy adult tissues and hemocytes after Micrococcus luteus and Vibrio anguillarum bacterial infections. The Yesso scallop MKKs (PyMKKs) were found to have highly conserved structural features compared to the MKK genes from other invertebrate species. Using qRT-PCR analysis, three distinct expression patterns were detected among the PyMKKs over the course of ten different developmental stages. In adult scallops, the majority of the PyMKKs were highly expressed in mantle, gill, muscle and hemocytes. The differential expression patterns of the five PyMKKs after M. luteus (Gram-positive) and V. anguillarum (Gram-negative) bacterial infections suggested their possible involvement in the innate immune response and provide the foundation and resource for the further study on innate immune response of MAPK signal pathway in mollusk.

Characterizations and expression analyses of NF-κB and Rel genes in the Yesso scallop (Patinopecten yessoensis) suggest specific response patterns against Gram-negative infection in bivalves.

Rel/NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) genes are evolutionarily conserved and play a pivotal role in several physiological events. They have been extensively studied from various species, including both vertebrates and invertebrates. However, the Rel/NF-κB genes have not been systematically characterized in bivalves. In this study, we identified and characterized PyNF-κB and PyRel in the Yesso scallop (Patinopecten yessoensis). Phylogenetic and protein structural analyses were conducted to determine the identities and evolutionary relationships of Rel/NF-κB genes in Yesso scallop. Compared with the Rel/NF-κB genes from vertebrate species, the PyNF-κB and PyRel are relatively conserved in their structural features, but there were no paralogs found in P. yessoensis or other invertebrates. To gain insights into the roles of Rel/NF-κB genes during the innate immune response in scallop, quantitative real-time PCR was used to investigate the expression profiles of these genes at different developmental stages, in healthy adult tissues and in the hemolymph after bacterial infection with Micrococcus luteus and Vibrio anguillarum. The real-time PCR results indicated the abundance of PyNF-κB in the first four embryonic stages, including oocytes, fertilized eggs, morulae and blastulae. By contrast, PyRel was abundantly expressed in blastulae, trochophores and D-shaped larvae. In adult scallops, PyNF-κB and PyRel were ubiquitously expressed in most healthy tissues and highly expressed in most of the immune related tissues. Both genes were significantly up-regulated during the acute phase (3 h) after infection with Gram-positive (M. luteus) and negative (V. anguillarum) bacteria, while the much higher expression level of PyNF-κB suggested the involvement of the extra immune deficiency (IMD)-like pathway against the Gram-negative bacterial infection. The complex pattern of Rel/NF-κB induced expression suggested that PyNF-κB and PyRel both have specific and cooperative roles in the acute immune responses to bacterial infection.

A scallop IGF binding protein gene: molecular characterization and association of variants with growth traits.

BACKGROUND: Scallops represent economically important aquaculture shellfish. The identification of genes and genetic variants related to scallop growth could benefit high-yielding scallop breeding. The insulin-like growth factor (IGF) system is essential for growth and development, with IGF binding proteins (IGFBPs) serving as the major regulators of IGF actions. Although an effect of IGF on growth was detected in bivalve, IGFBP has not been reported, and members of the IGF system have not been characterized in scallop. RESULTS: We cloned and characterized an IGFBP (PyIGFBP) gene from the aquaculture bivalve species, Yesso scallop (Patinopecten yessoensis, Jay, 1857). Its full-length cDNA sequence was 1,445 bp, with an open reading frame of 378 bp, encoding 125 amino acids, and its genomic sequence was 10,193 bp, consisting of three exons and two introns. The amino acid sequence exhibited the characteristics of IGFBPs, including multiple cysteine residues and relatively conserved motifs in the N-terminal and C-terminal domains. Expression analysis indicated that PyIGFBP was expressed in all the tissues and developmental stages examined, with a significantly higher level in the mantle than in other tissues and a significantly higher level in gastrulae and trochophore larvae than in other stages. Furthermore, three single nucleotide polymorphisms (SNPs) were identified in this gene. SNP c.1054A>G was significantly associated with both shell and soft body traits in two populations, with the highest trait values in GG type scallops and lowest in AG type ones. CONCLUSION: We cloned and characterized an IGFBP gene in a bivalve, and this report also represents the first characterizing an IGF system gene in scallops. A SNP associated with scallop growth for both the shell and soft body was identified in this gene. In addition to providing a candidate marker for scallop breeding, our results also suggest the role of PyIGFBP in scallop growth.

Identification of two secreted ferritin subunits involved in immune defense of Yesso scallop Patinopecten yessoensis.

As an important iron storage protein, ferritin plays a crucial role in the iron-withholding defense system. In this study, two secreted ferritin subunits (PyFerS1 and PyFerS2) were identified from the Yesso scallop, Patinopecten yessoensis. The complete DNA sequences of the two ferritins are 7101 and 5359 bp, consisting of seven and five exons, respectively. The full-length cDNAs of PyFerS1 and PyFerS2 are 960 and 956 bp in length, encoding 228 and 220 amino acids, respectively. They have typical ferritin structures, with four long α-helices, one short α-helix and an L-loop. Signal peptides were found at the N-terminus of both ferritins, and phylogenetic analysis showed that they both clustered with secreted mollusc ferritins. PyFerS1 possesses all seven conserved residues of the ferroxidase center, whereas PyFerS2 only has two. Real-time PCR analysis indicated high expression level of PyFerS2 in the D-shaped larvae, and PyFerS1 in both D-shaped larvae and fertilized eggs. In adult scallops, PyFerS1 was only detected in the hepatopancreas, whereas PyFerS2 was detected in both hepatopancreas and mantle. After the scallops were challenged by iron ion or bacteria Vibrio anguillarum, the expression of both PyFerS1 and PyFerS2 was significantly elevated, suggesting they may play a role in scallop innate immune defense. For the first time, secreted ferritins were cloned and comprehensively characterized in bivalve molluscs. It will assist in better understanding of the role of secreted ferritins in bivalve innate immunity.

Identification of reference genes for qRT-PCR analysis in Yesso scallop Patinopecten yessoensis.

BACKGROUND: Bivalves comprise around 30,000 extant species and have received much attention for their importance in ecosystems, aquaculture and evolutionary studies. Despite the increasing application of real-time quantitative reverse transcription PCR (qRT-PCR) in gene expression studies on bivalve species, little research has been conducted on reference gene selection which is critical for reliable and accurate qRT-PCR analysis. For scallops, systematic evaluation of reference genes that can be used among tissues or embryo/larva stages is lacking, and ß-actin (ACT) is most frequently used as qRT-PCR reference gene without validation. RESULTS: In this study, 12 commonly used candidate reference genes were selected from the transcriptome data of Yesso scallop (Patinopectenyessoensis) for suitable qRT-PCR reference genes identification. The expression of these genes in 36 tissue samples and 15 embryo/larva samples under normal physiological conditions was examined by qRT-PCR, and their expression stabilities were evaluated using three statistic algorithms, geNorm, NormFinder, and comparative ∆Ct method. Similar results were obtained by the three approaches for the most and the least stably expressed genes. Final comprehensive ranking for the 12 genes combing the results from the three programs showed that, for different tissues, DEAD-box RNA helicase (HELI), ubiquitin (UBQ), and 60S ribosomal protein L16 (RPL16) were the optimal reference genes combination, while for different embryo/larva stages, gene set containing Cytochrome B (CB), Cytochrome C (CC), Histone H3.3 (His3.3), and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were recommended for qRT-PCR normalization. ACT was among the least stable genes for both adult tissues and embryos/larvae. CONCLUSIONS: This work constitutes the first systematic analysis on reference genes selection for qRT-PCR normalization in scallop under normal conditions. The suitable reference genes we recommended will be useful for the identification of genes related to biological processes in Yesso scallop, and also in the reference gene selection for other scallop or bivalve species.

Identification and characterization of four ferritin subunits involved in immune defense of the Yesso scallop (Patinopecten yessoensis).

As a primary iron storage protein, ferritin plays a vital role in iron homeostasis and innate immunity. In this study, four ferritin subunits (PyFer1, PyFer2, PyFer3, and PyFer4) were cloned from the Yesso scallop, Patinopecten yessoensis, by rapid amplification of cDNA ends (RACE) following in silico transcriptome analysis. The full-length cDNAs of the four ferritins are 895, 920, 891, and 1400 bp in length, respectively, and each contains a putative iron response element (IRE) in its 5' UTR. Meanwhile, multiple A+U-destabilizing elements (TATT or ATTTA) are present in the 3' UTRs of PyFer2 and PyFer4. The open reading frames of the four ferritins are 522, 516, 516, and 519 bp, encoding 173, 171, 171, and 172 amino acids, respectively. These proteins have typical ferritin structures, with four long α-helices, one short α-helix and an L-loop. All of the predicted proteins possess both the ferroxidase center of mammalian H ferritins (E25, Y32, E59, E60, H63, E105, and Q139) and the iron nucleation site of mammalian L ferritins (H116, D129, and E132), and the recombinant proteins possess apparent ferroxidase activity. Quantitative real-time PCR analysis revealed that the expression of the four PyFers was significantly elevated at the D-shaped stage and was relatively high in the adult mantle and hepatopancreas. Furthermore, the four PyFers were significantly up-regulated by iron or bacterial challenge, and all four purified recombinant PyFers were able to inhibit the growth of the scallop pathogen Vibrio anguillarum. These results suggest that these PyFers are likely to play important roles in many fundamental biological processes in P. yessoensis, including immune defense, iron homeostasis, and shell development.