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The development of digital pathology and progression of state‐of‐the‐art algorithms for computer vision have led to increasing interest in the use of artificial intelligence (AI), especially deep learning (DL)‐based AI, in tumor pathology. The DL‐based algorithms have been developed to conduct all kinds of work involved in tumor pathology, including tumor diagnosis, subtyping, grading, staging, and prognostic prediction, as well as the identification of pathological features, biomarkers and genetic changes. The applications of AI in pathology not only contribute to improve diagnostic accuracy and objectivity but also reduce the workload of pathologists and subsequently enable them to spend additional time on high‐level decision‐making tasks. In addition, AI is useful for pathologists to meet the requirements of precision oncology. However, there are still some challenges relating to the implementation of AI, including the issues of algorithm validation and interpretability, computing systems, the unbelieving attitude of pathologists, clinicians and patients, as well as regulators and reimbursements. Herein, we present an overview on how AI‐based approaches could be integrated into the workflow of pathologists and discuss the challenges and perspectives of the implementation of AI in tumor pathology.

Multiple studies have indicated that cathepsins (Cats) play a crucial role in the development and progression of skin cancer. However, most of these studies are observational and may be influenced by external variables, necessitating further research to establish causal relationships. We conducted a two-sample, two-way Mendelian randomization (MR) study utilizing pooled data from genome-wide association studies (GWAS) to evaluate the causal association between 9 Cats (Cat-B, E, F, G, H, L2, O, S, and Z) and 3 types of skin cancer, including malignant melanoma (MM), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Our analysis employed several methods, including inverse variance weighting (IVW), MR-Egger, weighted median, Cochran's test, the MR-Egger intercept test, and leave-one-out sensitivity analysis. Furthermore, bioinformatics analysis of loci linked to Cats and skin cancer was performed to explore potential molecular mechanisms. Genetically predicted increases in Cat-F and Cat-O levels were found to be correlated with a higher risk of BCC, while increased levels of Cat-L2 and Cat-O were associated with a reduced incidence of SCC. Bioinformatics analysis suggested that differentially expressed genes located near Cats-related loci could potentially influence BCC and SCC by modulating relevant signaling pathways and the tumor microenvironment. Our research indicated a causal link between Cats and skin cancer. By conducting a bioinformatic analysis of genetic loci related to Cats and skin cancer, we were able to gain a better understanding of the potential molecular mechanisms driving this association. This research can provide valuable insights into the diagnosis and treatment of skin cancer.

Chitinases represent an alternative therapeutic target for opportunistic invasive mycosis since they are necessary for fungal cell wall remodeling. This study presents the design of new chitinase inhibitors from a known hydrolysis intermediate. Firstly, a bioinformatic analysis of Aspergillus fumigatus chitinase B1 (AfChiB1) and chitotriosidase (CHIT1) by length and conservation was done to obtain consensus sequences, and molecular homology models of fungi and human chitinases were built to determine their structural differences. We explored the octahydroisoindolone scaffold as a potential new antifungal series by means of its structural and electronic features. Therefore, we evaluated several synthesis-safe octahydroisoindolone derivatives by molecular docking and evaluated their AfChiB1 interaction profile. Additionally, compounds with the best interaction profile (1–5) were docked within the CHIT1 catalytic site to evaluate their selectivity over AfChiB1. Furthermore, we considered the interaction energy (MolDock score) and a lipophilic parameter (aLogP) for the selection of the best candidates. Based on these descriptors, we constructed a mathematical model for the IC50 prediction of our candidates (60–200 μM), using experimental known inhibitors of AfChiB1. As a final step, ADME characteristics were obtained for all the candidates, showing that 5 is our best designed hit, which possesses the best pharmacodynamic and pharmacokinetic character.

Small ubiquitin-related modifier (SUMO) regulates the cellular function of diverse proteins through post-translational modifications. The current study defined a new homolog of SUMO genes in the rice genome and named it OsSUMO7. Putative protein analysis of OsSUMO7 detected SUMOylation features, including di-glycine (GG) and consensus motifs (ΨKXE/D) for the SUMOylation site. Phylogenetic analysis demonstrated the high homology of OsSUMO7 with identified rice SUMO genes, which indicates that the OsSUMO7 gene is an evolutionarily conserved SUMO member. RT-PCR analysis revealed that OsSUMO7 was constitutively expressed in all plant organs. Bioinformatic analysis defined the physicochemical properties and structural model prediction of OsSUMO7 proteins. A red fluorescent protein (DsRed), fused with the OsSUMO7 protein, was expressed and localized mainly in the nucleus and formed nuclear subdomain structures. The fusion proteins of SUMO-conjugating enzymes with the OsSUMO7 protein were co-expressed and co-localized in the nucleus and formed nuclear subdomains. This indicated that the OsSUMO7 precursor is processed, activated, and transported to the nucleus through the SUMOylation system of the plant cell.

The regenerative capacity of peripheral nerves is limited after nerve injury. A number of growth factors modulate many cellular behaviors, such as proliferation and migration, and may contribute to nerve repair and regeneration. Our previous study observed the dynamic changes of genes in L4-6 dorsal root ganglion after rat sciatic nerve crush using transcriptome sequencing. Our current study focused on upstream growth factors and found that a total of 19 upstream growth factors were dysregulated in dorsal root ganglions at 3, 9 hours, 1, 4, or 7 days after nerve crush, compared with the 0 hour control. Thirty-six rat models of sciatic nerve crush injury were prepared as described previously. Then, they were divided into six groups to measure the expression changes of representative genes at 0, 3, 9 hours, 1, 4 or 7 days post crush. Our current study measured the expression levels of representative upstream growth factors, including nerve growth factor, brain-derived neurotrophic factor, fibroblast growth factor 2 and amphiregulin genes, and explored critical signaling pathways and biological process through bioinformatic analysis. Our data revealed that many of these dysregulated upstream growth factors, including nerve growth factor, brain-derived neurotrophic factor, fibroblast growth factor 2 and amphiregulin, participated in tissue remodeling and axon growth-related biological processes Therefore, the experiment described the expression pattern of upstream growth factors in the dorsal root ganglia after peripheral nerve injury. Bioinformatic analysis revealed growth factors that may promote repair and regeneration of damaged peripheral nerves. All animal surgery procedures were performed in accordance with Institutional Animal Care Guidelines of Nantong University and ethically approved by the Administration Committee of Experimental Animals, China (approval No. 20170302-017) on March 2, 2017.

Background: Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user’s health but also poses risks and costs to society. Prolonged METH dependence has been shown to impair cognition, which may be the primary factor in impulsive drug-seeking behaviors and high relapse rates. However, the molecular mechanisms underlying METH addiction and METH-induced cognitive decline remain poorly understood. Methods: To illuminate the potential molecular mechanisms underpinning METH addiction, we compared serum protein expression levels between 12 long-term METH users and 12 healthy controls using label-free quantitative proteomics. Bioinformatic analyses were conducted to determine functional networks and protein-protein interactions. Results: In total, 23 differentially expressed proteins were identified between the two groups. The differentially expressed proteins were related to cognitive dysfunction, neuroinflammation, immune impairment, metabolic disturbances, and calcium binding and regulation. Conclusions: These 23 proteins may underpin the multi-system damage induced by chronic METH exposure. Our findings provide novel insights into the molecular basis of METH addiction and inform potential prevention and treatment strategies for individuals with METH dependence.

Neuropathic pain is a complex chronic condition occurring post-nervous system damage. The transcriptional reprogramming of injured dorsal root ganglia (DRGs) drives neuropathic pain. However, few comparative analyses using high-throughput platforms have investigated uninjured DRG in neuropathic pain, and potential interactions among differentially expressed genes (DEGs) and pathways were not taken into consideration. The aim of this study was to identify changes in genes and pathways associated with neuropathic pain in uninjured L4 DRG after L5 spinal nerve ligation (SNL) by using bioinformatic analysis. The microarray profile GSE24982 was downloaded from the Gene Expression Omnibus database to identify DEGs between DRGs in SNL and sham rats. The prioritization for these DEGs was performed using the Toppgene database followed by gene ontology and pathway enrichment analyses. The relationships among DEGs from the protein interactive perspective were analyzed using protein-protein interaction (PPI) network and module analysis. Real-time polymerase chain reaction (PCR) and Western blotting were used to confirm the expression of DEGs in the rodent neuropathic pain model. A total of 206 DEGs that might play a role in neuropathic pain were identified in L4 DRG, of which 75 were upregulated and 131 were downregulated. The upregulated DEGs were enriched in biological processes related to transcription regulation and molecular functions such as DNA binding, cell cycle, and the FoxO signaling pathway. Ctnnb1 protein had the highest connectivity degrees in the PPI network. The in vivo studies also validated that mRNA and protein levels of Ctnnb1 were upregulated in both L4 and L5 DRGs. This study provides insight into the functional gene sets and pathways associated with neuropathic pain in L4 uninjured DRG after L5 SNL, which might promote our understanding of the molecular mechanisms underlying the development of neuropathic pain.

Previous research revealed the positive activity of matrix metalloproteinase 7 (MMP7) on migration and myelin regeneration of Schwann cells (SCs). However, understanding of the molecular changes and biological activities induced by increased amounts of MMP7 in SCs remains limited. To better understand the underlying molecular events, primary SCs were isolated from the sciatic nerve stump of newborn rats and cultured with 10 nM human MMP7 for 24 hours. The results of genetic testing were analyzed at a relatively relaxed threshold value (fold change ≥ 1.5 and P-value < 0.05). Upon MMP7 exposure, 149 genes were found to be upregulated in SCs, whereas 133 genes were downregulated. Gene Ontology analysis suggested that many differentially expressed molecules were related to cellular processes, single-organism processes, and metabolic processes. Kyoto Enrichment of Genes and Genomes pathway analysis further indicated the critical involvement of cell signaling and metabolism in MMP7-induced molecular regulation of SCs. Results of Ingenuity Pathway Analysis (IPA) also revealed that MMP7 regulates biological processes, molecular functions, cellular components, diseases and functions, biosynthesis, material metabolism, cell movement, and axon guidance. The outcomes of further analysis will deepen our comprehension of MMP7-induced biological changes in SCs. This study was approved by the Laboratory Animal Ethics Committee of Nantong University, China (approval No. 20190225-004) on February 27, 2019.

Gastric cancer is one of the most common malignant tumors worldwide; however, the efficacy of clinical treatment is limited. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been reported to play a key role in the development of cancer. They also provide novel candidates for targeted therapy. To date, in-depth studies on the molecular mechanisms of gastric cancer involving miRNAs are still absent. We previously reported that 5 miRNAs were identified as being significantly increased in gastric cancer, and the role of these miRNAs was investigated in the present study. By using bioinformatics tools, we found that more than 4,000 unique genes are potential downstream targets of gastric cancer miRNAs, and these targets belong to the protein class of nucleic acid binding, transcription factor, enzyme modulator, transferase and receptor. Pathway mapping showed that the targets of gastric cancer miRNAs are involved in the MAPK signaling pathway, pathways in cancer, the PI3K-Akt signaling pathway, the HTLV-1 signaling pathway and Ras signaling pathway, thus regulating cell growth, differentiation, apoptosis and metastasis. Analysis of the pathways related to miRNAs may provides potential drug targets for future therapy of gastric cancer.

Wallerian degeneration is a critical biological process that occurs in distal nerve stumps after nerve injury. To systematically investigate molecular changes underlying Wallerian degeneration, we used a rat sciatic nerve transection model to examine microarray analysis outcomes and investigate significantly involved Kyoto Enrichment of Genes and Genomes（KEGG） pathways in injured distal nerve stumps at 0, 0.5, 1, 6, 12, and 24 hours, 4 days, 1, 2, 3, and 4 weeks after peripheral nerve injury. Bioinformatic analysis showed that only one KEGG pathway（cytokine-cytokine receptor interaction） was significantly enriched at an early time point（1 hour post-sciatic nerve transection）. At later time points, the number of enriched KEGG pathways initially increased and then decreased. Three KEGG pathways were studied in further detail： cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and axon guidance. Moreover, temporal expression patterns of representative differentially expressed genes in these KEGG pathways were validated by real time-polymerase chain reaction. Taken together, the above three signaling pathways are important after sciatic nerve injury, and may increase our understanding of the molecular mechanisms underlying Wallerian degeneration.