SSLDTI: A novel method for drug-target interaction prediction based on self-supervised learning.

Many computational methods have been proposed to identify potential drug-target interactions (DTIs) to expedite drug development. Graph neural network (GNN) methods are considered to be one of the most effective approaches. However, shallow GNN methods can only aggregate local information from nodes. Also, deep GNN methods may result in over-smoothing while obtaining long-distance neighbourhood information. As a result, existing GNN methods struggle to extract the complete features of the graph. Additionally, the number of known DTIs is insufficient, and there are far more unknown drug-target pairs than known DTIs, leading to class imbalance. This article proposes a model that combines graph autoencoder and self-supervised learning to accurately encode multilevel features of graphs using only a small number of labelled samples. We introduce a positive sample compensation coefficient to the objective function to mitigate the impact of class imbalance. Experiments on two datasets demonstrated that our model outperforms the four baseline methods, and the new DTIs predicted by the SSLDTI model were verified by the DrugBank database.

Preclinical long-term safety of intraspinal transplantation of human dorsal spinal GABA neural progenitor cells.

Human pluripotent stem cell (hPSC)-derived neurons have shown promise in treating spinal cord injury (SCI). We previously showed that hPSC-derived dorsal spinal γ-aminobutyric acid (GABA) neurons can alleviate spasticity and promote locomotion in rats with SCI, but their long-term safety remains elusive. Here, we characterized the long-term fate and safety of human dorsal spinal GABA neural progenitor cells (NPCs) in naive rats over one year. All grafted NPCs had undergone differentiation, yielding mainly neurons and astrocytes. Fully mature human neurons grew many axons and formed numerous synapses with rat neural circuits, together with mature human astrocytes that structurally integrated into the rat spinal cord. The sensorimotor function of rats was not impaired by intraspinal transplantation, even when human neurons were activated or inhibited by designer receptors exclusively activated by designer drugs (DREADDs). These findings represent a significant step toward the clinical translation of human spinal neuron transplantation for treating SCI.

An adaptive collision avoidance strategy for autonomous vehicle under various road friction and speed.

When the autonomous vehicle (AV) is under various road friction and speed, emergency collision avoidance is extremely difficult. In this situation, the AV may encounter severe understeering problem, so it is hard to achieve collision avoidance, even under the control of active safety system. To tackle this problem, an adaptive collision avoidance strategy (ACAS) is proposed for AV under various road friction and speed. The adaptive performance of the ACAS is realized via three aspects. (1) An adaptive reference path planning method is proposed to provide desired evasive speed and reference path for the AV according to various road friction and reduces the turning burden of AV. (2) A predictive-based fuzzy controller is designed to realize the speed control, and it improves the tracking accuracy of various desired evasive speed. (3) A novel turning enhanced method built with a direct yaw turning controller and a torque distribution method can enhance the turning capability of AV. Finally, the proposed strategy is verified on AV via simulation experiments. The code can be found online here: https://github.com/wangjinlei-hnu/ACAS.

PreCanCell: An ensemble learning algorithm for predicting cancer and non-cancer cells from single-cell transcriptomes.

We propose PreCanCell, a novel algorithm for predicting malignant and non-malignant cells from single-cell transcriptomes. PreCanCell first identifies the differentially expressed genes (DEGs) between malignant and non-malignant cells commonly in five common cancer types-associated single-cell transcriptome datasets. The five common cancer types include renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), melanoma, lung adenocarcinoma (LUAD), and breast cancer (BC). With each of the five datasets as the training set and the DEGs as the features, a single cell is classified as malignant or non-malignant by k-NN (k = 5). Finally, the single cell is determined as malignant or non-malignant by the majority vote of the five k-NN classification results. We tested the predictive performance of PreCanCell in 19 single-cell datasets, and reported classification accuracy, sensitivity, specificity, balanced accuracy (the average of sensitivity and specificity) and the area under the receiver operating characteristic curve (AUROC). In all these datasets, PreCanCell achieved above 0.8 accuracy, sensitivity, specificity, balanced accuracy and AUROC. Finally, we compared the predictive performance of PreCanCell with that of seven other algorithms, including CHETAH, SciBet, SCINA, scmap-cell, scmap-cluster, SingleR, and ikarus. Compared to these algorithms, PreCanCell displays the advantages of higher accuracy and simpler implementation. We have developed an R package for the PreCanCell algorithm, which is available at https://github.com/WangX-Lab/PreCanCell.

Efficacy and safety of NAHAO® hydrogel in amelioration of chemoradiotherapy-induced oral mucositis: An preliminary clinical study (ChiCTR2200064766).

OBJECTIVE: To evaluate the efficacy of NAHAO® oral mucosal antibacterial care solution (NAHAO® spray) on attenuating oral mucositis (OM) symptoms and related mechanisms investigation. MATERIAL AND METHODS: Experimental OM models were established by acetic acid and 5-fluorouracil combined with mechanical trauma. We investigated spontaneous pain of conscious OM rats after using NAHAO®. The expression of NF-κB in affected trigeminal ganglion was measured by western blot. In clinical study, 60 patients who developed post-treatment OM of grade 2 or above or persistent mucosal pain with a score equal to or greater than 4 points were selected. All patients were required to receive NAHAO® spray 8 times a day and were examined for OM degrees and oral mucosal pain scores before and after application. RESULTS: Experimental data from experimental model suggested that clinical efficacy of NAHAO® spray was involved in inflammation inhibition via NF-κB pathway. The results of clinical study showed that NAHAO® spray improved the symptoms of OM, there is statistically significant difference in oral mucosal pain scores after treated with NAHAO, and the dietary restrictions were also improved. CONCLUSION: NAHAO® spray alleviates pain and improves the diet situation in OM patients, which is partly mediated through the inhibition of NF-κB pathway.

Acute myocardial infarction after inactivated COVID-19 vaccination: a case report and literature review.

A number of vaccines have been developed and deployed globally to restrain the spreading of the coronavirus disease 2019 (COVID-19). The adverse effect following vaccination is an important consideration. Acute myocardial infarction (AMI) is a kind of rare adverse event after COVID-19 vaccination. Herein, we present a case of an 83-year-old male who suffered cold sweat ten minutes after the first inactivated COVID-19 vaccination and AMI one day later. The emergency coronary angiography showed coronary thrombosis and underlying stenosis in his coronary artery. Type II Kounis syndrome might be a potential mechanism, which is manifested as coronary thrombosis secondary to allergic reactions in patients with underlying asymptomatic coronary heart disease. We also summarize the reported AMI cases post COVID-19 vaccination, as well as overview and discuss the proposed mechanisms of AMI after COVID-19 vaccination, thus providing insights for clinicians to be aware of the possibility of AMI following COVID-19 vaccination and potential underlying mechanisms.

Inhibition of CXorf56 promotes PARP inhibitor-induced cytotoxicity in triple-negative breast cancer.

Poly(ADP-ribose) polymerase inhibitors (PARPis) induce DNA lesions that preferentially kill homologous recombination (HR)-deficient breast cancers induced by BRCA mutations, which exhibit a low incidence in breast cancer, thereby limiting the benefits of PARPis. Additionally, breast cancer cells, particularly triple-negative breast cancer (TNBC) cells, exhibit HR and PARPi resistance. Therefore, targets must be identified for inducing HR deficiency and sensitizing cancer cells to PARPis. Here, we reveal that CXorf56 protein increased HR repair in TNBC cells by interacting with the Ku70 DNA-binding domain, reducing Ku70 recruitment and promoting RPA32, BRCA2, and RAD51 recruitment to sites of DNA damage. Knockdown of CXorf56 protein suppressed HR in TNBC cells, specifically during the S and G2 phases, and increased cell sensitivity to olaparib in vitro and in vivo. Clinically, CXorf56 protein was upregulated in TNBC tissues and associated with aggressive clinicopathological characteristics and poor survival. All these findings indicate that treatment designed to inhibit CXorf56 protein in TNBC combined with PARPis may overcome drug resistance and expand the application of PARPis to patients with non-BRCA mutantion.

Genomic and genetic advances of oiltea-camellia (Camellia oleifera).

Oiltea-camellia (C. oleifera) is a widely cultivated woody oil crop in Southern China and Southeast Asia. The genome of oiltea-camellia was very complex and not well explored. Recently, genomes of three oiltea-camellia species were sequenced and assembled, multi-omic studies of oiltea-camellia were carried out and provided a better understanding of this important woody oil crop. In this review, we summarized the recent assembly of the reference genomes of oiltea-camellia, genes related to economic traits (flowering, photosynthesis, yield and oil component), disease resistance (anthracnose) and environmental stress tolerances (drought, cold, heat and nutrient deficiency). We also discussed future directions of integrating multiple omics for evaluating genetic resources and mining key genes of important traits, and the application of new molecular breeding and gene editing technologies to accelerate the breeding process of oiltea-camellia.

Study on different sequences of painless gastroenteroscopy in patients with difficult airway.

The selection of different examination sequences of painless gastroscopy in patients with difficult airway risk was explored in this study. A total of 45 patients undergoing painless gastroscopy with Mallampati airway score of III-IV were randomly assigned into two groups (A group and B group) according to the sequence of colonoscopy and gastroscopy. Group A was first examined by gastroscopy after anesthesia, and then by colonoscopy. Group B was examined in the opposite order, first by colonoscopy, and then by gastroscopy. Ramsay Sedation scores were evaluated every five minutes when gastroscopy was performed in the two groups. The dosage of propofol, blood pressure, heart rate, blood oxygen saturation, recovery time, hospital leaving time, and adverse reactions after induction and endoscopy were recorded. The dosage of propofol and change of vital signs in B group was less than that in A group. Operation time, recovery time, hospital leaving time and postoperative adverse reactions have no significant difference between two groups. For patients at risk of difficult airway, colonoscopy followed by gastroscopy has more stable intraoperative vital signs and less propofol consumption.

Human spinal GABA neurons survive and mature in the injured nonhuman primate spinal cord.

Spinal cord injury (SCI) leads to permanent neural dysfunction without effective therapies. We previously showed that human pluripotent stem cell (hPSC)-derived spinal GABA neurons can alleviate spasticity and promote locomotion in rats after SCI, but whether this strategy can be translated into the clinic remains elusive. Here, a nonhuman primate (NHP) model of SCI was established in rhesus macaques (Macaca mulatta) in which the T10 spinal cord was hemisected, resulting in neural conduction failure and neural dysfunction, including locomotion deficits, pain, and spasms. Grafted human spinal GABA neurons survived for up to 7.5 months in the injured monkey spinal cord and retained their intrinsic properties, becoming mature and growing axons and forming synapses. Importantly, they are functionally alive, as evidenced by designer receptors exclusively activated by designer drug (DREADD) activation. These findings represent a significant step toward the clinical translation of human spinal neuron transplantation for treating SCI.

Nomogram for prediction of peritoneal metastasis risk in colorectal cancer.

Objective: Peritoneal metastasis is difficult to diagnose using traditional imaging techniques. The main aim of the current study was to develop and validate a nomogram for effectively predicting the risk of peritoneal metastasis in colorectal cancer (PMCC). Methods: A retrospective case-control study was conducted using clinical data from 1284 patients with colorectal cancer who underwent surgery at the First Affiliated Hospital of Guangxi Medical University from January 2010 to December 2015. Least absolute shrinkage and selection operator (LASSO) regression was applied to optimize feature selection of the PMCC risk prediction model and multivariate logistic regression analysis conducted to determine independent risk factors. Using the combined features selected in the LASSO regression model, we constructed a nomogram model and evaluated its predictive value via receiver operating characteristic (ROC) curve analysis. The bootstrap method was employed for repeated sampling for internal verification and the discrimination ability of the prediction models evaluated based on the C-index. The consistency between the predicted and actual results was assessed with the aid of calibration curves. Results: Overall, 96 cases of PMCC were confirmed via postoperative pathological diagnosis. Logistic regression analysis showed that age, tumor location, perimeter ratio, tumor size, pathological type, tumor invasion depth, CEA level, and gross tumor type were independent risk factors for PMCC. A nomogram composed of these eight factors was subsequently constructed. The calibration curve revealed good consistency between the predicted and actual probability, with a C-index of 0.882. The area under the curve (AUC) of the nomogram prediction model was 0.882 and its 95% confidence interval (CI) was 0.845-0.919. Internal validation yielded a C-index of 0.868. Conclusion: We have successfully constructed a highly sensitive nomogram that should facilitate early diagnosis of PMCC, providing a robust platform for further optimization of clinical management strategies.

CPACK: An Intelligent Cyber-Physical Access Control Kit for Protecting Network.

Access Control Lists (ACL) are critical to protecting network and cyber-physical systems. Traditional firewalls mostly use reactive methods to enforce ACLs, so that new ACL updates cannot take effect immediately. In this paper, based on our previous work, we propose CPACK, an intelligent cyber-physical access control kit, which uses a smart algorithm to upgrade the ACL list. CPACK adopts a proactive way to enforce ACL and reacts to a new ACL update and network view update in real time. We implement CPACK on both Floodlight and ONOS controller. We then conduct a large number of experiments to compare CPACK with the Floodlight firewall application. The experimental results show that CPACK has a better performance than the existing Floodlight firewall application. CPACK is also integrated into the new version of Floodlight and ONOS controller.

Identification of key molecules in COVID-19 patients significantly correlated with clinical outcomes by analyzing transcriptomic data.

Background: Although several key molecules have been identified to modulate SARS-CoV-2 invasion of human host cells, the molecules correlated with outcomes in COVID-19 caused by SARS-CoV-2 infection remain insufficiently explored. Methods: This study analyzed three RNA-Seq gene expression profiling datasets for COVID-19 and identified differentially expressed genes (DEGs) between COVID-19 patients and normal people, commonly in the three datasets. Furthermore, this study explored the correlation between the expression of these genes and clinical features in COVID-19 patients. Results: This analysis identified 13 genes significantly upregulated in COVID-19 patients' leukocyte and SARS-CoV-2-infected nasopharyngeal tissue compared to normal tissue. These genes included OAS1, OAS2, OAS3, OASL, HERC6, SERPING1, IFI6, IFI44, IFI44L, CMPK2, RSAD2, EPSTI1, and CXCL10, all of which are involved in antiviral immune regulation. We found that these genes' downregulation was associated with worse clinical outcomes in COVID-19 patients, such as intensive care unit (ICU) admission, mechanical ventilatory support (MVS) requirement, elevated D-dimer levels, and increased viral loads. Furthermore, this analysis identified two COVID-19 clusters based on the expression profiles of the 13 genes, termed COV-C1 and COV-C2. Compared with COV-C1, COV-C2 more highly expressed the 13 genes, had stronger antiviral immune responses, were younger, and displayed more favorable clinical outcomes. Conclusions: A strong antiviral immune response is essential in reducing severity of COVID-19.

Evaluation of the role of vaccination in the COVID-19 pandemic based on the data from the 50 U.S. States.

Vaccination is considered as the ultimate weapon to end the pandemic. However, the role of vaccines in the pandemic remains controversial. To explore the impact of vaccination on the COVID-19 pandemic, we used logistic regression models to predict numbers of population-adjusted confirmed cases, deaths, intensive care unit (ICU) cases, case fatality rates and ICU admission rates of COVID-19 in the 50 U.S. states, based on 17 related variables. The logistic regression analysis showed that percentages of people vaccinated correlated inversely with the numbers of COVID-19 deaths and case fatality rates but showed no significant correlation with numbers of confirmed cases or ICU cases, or ICU admission rates. The Spearman correlation analysis showed that the percentages of people vaccinated correlated inversely with the numbers of COVID-19 deaths, ICU cases, ICU case rates, and case fatality rates but showed no significant correlation with numbers of confirmed cases. The number of deaths and mortality in the group after the vaccine usage were significantly lower than those in the group before the vaccine usage. However, after delta became the dominant strain, there were no longer significant differences in the number of deaths and the mortality rate between before and after delta became the dominant strain, although vaccines were used in both periods. Vaccination can significantly reduce COVID-19 deaths and mortality, while it cannot reduce the risk of COVID-19 infection. In addition to vaccination, other measures, such as social distancing, remain important in containing COVID-19 transmission and lower the risk of COVID-19 severe outcomes.

The bacteria inside human cancer cells: Mainly as cancer promoters.

The roles of the microbiome in human beings have become clearer with the development of next-generation sequencing techniques. Several pieces of evidence showed strong correlations between the microbiome and human health and disease, such as metabolic disorders, infectious diseases, digestive system diseases, and cancers. Among these diverse microbiomes, the role of bacteria in human cancers, especially in cancer cells, has received extensive attention. Latest studies found that bacteria widely existed in cancers, mainly in cancer cells and immune cells. In this review, we summarize the latest advances in understanding the role of bacteria in human cancer cells. We also discuss how bacteria are transported into cancer cells and their physiological significance in cancer progression. Finally, we present the prospect of bacterial therapy in cancer treatment.

METTL3 promotes colorectal cancer metastasis by stabilizing PLAU mRNA in an m6A-dependent manner.

Colorectal cancer (CRC) is one of the most common tumors and ranks second in tumor mortality. N6-methyladenosine (m6A) modification is the most prevalent RNA modification in eukaryotes. As the critical m6A methyltransferase, the role of METTL3 in the metastasis regulation of CRC might be controversial and need to be further explored. In this study, we confirmed that METTL3 could promoted CRC metastasis in vitro and in vivo. METTL3 was upregulated in CRC tissues and led to poor survival in CRC metastasis. We found METTL3 upregulated PLAU mRNA in an m6A-dependent manner, and then participated in MAPK/ERK pathway to promote angiogenesis and metastasis in CRC. Our study provided new therapeutic targets in CRC metastasis treatment.

Novel immune subtypes identification of HER2-positive breast cancer based on immunogenomic landscape.

HER2 positive BC is heterogeneous. But few studies discussed the classification of HER2-positive BC based on immune-related signatures. Using three publicly BC genomics datasets, we classified HER2 positive BC based on 33 immune-related signatures and used unsupervised machine learning methods to predict and perform the classification. We grouped three HER2-positive BC subtypes that we called Immune-High (IM-H), Immune-Medium (IM-M), and Immune-Low (IM-L), and manifested this categorization was predictable, duplicable and reliable by analyzing another dataset. Compared to other subtypes, IM-H had a higher immune cell infiltration level and stronger anti-tumor immune activities, as well as better clinical survival outcome. Besides these signatures, there were some cancer-related pathways which were hyperactivated in IM-H, including cytokine-cytokine receptor interactions, antigen processing and presentation pathways, natural killer cell-mediated cytotoxicity, Th1 and Th2 cell differentiation, chemokine signaling pathway, Th17 cell differentiation, B and T cell receptor signaling, NF-kappa B signaling, PD-L1 expression and PD-1 checkpoint pathway in cancer, TNF signaling, IL-17 signaling, NOD-like receptor signaling and Toll-like receptor signaling. By contrast, IM-L showed depressed immune-related signatures and enhanced activation of lycosylphosphatidylinositol-anchor biosynthesis and mismatch repair. Moreover, we discovered a gene co-expression network focused on eight transcription factor genes (EOMES, TBX21, GFI1, IRF4, POU2AF1, CIITA, FOXP3 and TOX) and one tumor suppress gene (PRF1), which were closely related with tumor immune. We identified three HER2-positive BC subtypes based on immune-related signatures, which had potential clinical implications and promoted the optimal stratification of HER2-positive BC responsive to immunotherapy.

Autophagy and cancer treatment: four functional forms of autophagy and their therapeutic applications.

Cancer is the leading cause of death worldwide. Drugs play a pivotal role in cancer treatment, but the complex biological processes of cancer cells seriously limit the efficacy of various anticancer drugs. Autophagy, a self-degradative system that maintains cellular homeostasis, universally operates under normal and stress conditions in cancer cells. The roles of autophagy in cancer treatment are still controversial because both stimulation and inhibition of autophagy have been reported to enhance the effects of anticancer drugs. Thus, the important question arises as to whether we should try to strengthen or suppress autophagy during cancer therapy. Currently, autophagy can be divided into four main forms according to its different functions during cancer treatment: cytoprotective (cell survival), cytotoxic (cell death), cytostatic (growth arrest), and nonprotective (no contribution to cell death or survival). In addition, various cell death modes, such as apoptosis, necrosis, ferroptosis, senescence, and mitotic catastrophe, all contribute to the anticancer effects of drugs. The interaction between autophagy and these cell death modes is complex and can lead to anticancer drugs having different or even completely opposite effects on treatment. Therefore, it is important to understand the underlying contexts in which autophagy inhibition or activation will be beneficial or detrimental. That is, appropriate therapeutic strategies should be adopted in light of the different functions of autophagy. This review provides an overview of recent insights into the evolving relationship between autophagy and cancer treatment.

LncRNA AZIN1-AS1 ameliorates myocardial ischemia-reperfusion injury by targeting miR-6838-5p/WNT3A axis to activate Wnt-ß/catenin signaling pathway.

Myocardial reperfusion, the effective therapy for acute myocardial infarction (AMI), commonly leads to myocardial ischemia/reperfusion (I/R) injury. The effects and functional mechanisms of LncRNA AZIN1-AS1 on myocardial I/R injury in vivo and vitro are not uncovered. In our present study, we established myocardial I/R injury model of mice and H/R injury model of cardiomyocytes and we discovered AZIN1-AS1 was decreased but miR-6838-5p was increased significantly in myocardial tissues injured by I/R treatment and H9c2 cells injured by hypoxia/reoxygenation (H/R) treatment. Silencing AZIN1-AS1 down-regulated cell viability but up-regulated apoptosis rate and CK-MB in addition LDH release of cardiomyocyte under H/R injury. However, overexpression of AZIN1-AS1 recovered abovementioned effects. Additionally, miR-6838-5p was found to be the direct target of AZIN1-AS1 and exhibited negative correlation with AZIN1-AS1. Moreover, miR-6838-5p inhibitor effectively eliminated the effects of AZIN1-AS1 knockdown on H/R-injured myocardial cells. Further experiments showed that WNT3A was the target of miR-6838-5p axis and overexpression of WNT3A also counteracted the roles of AZIN1-AS1 knockdown. Furthermore, knockdown of AZIN1-AS1 dramatically inhibited the activity of WNT-ß/catenin signaling pathway, which was recovered effectively by plasmid with overexpressing WNT3A. Therefore, this study firstly revealed that LncRNA AZIN1-AS1/miR-6838 axis inhibited apoptosis by activating WNT/ß-catenin pathway to protect mice or H9c2 cell from I/R-induced or H/R-induced injury respectively, which advised that AZIN1-AS1 could be regarded as a potential target for treating patients with AMI.

Begoniaparvibracteata, a new species in Begonia sect. Platycentrum (Begoniaceae) from Guangxi of China, based on morphological and molecular evidence.

The previously reported begonias in a limestone forest of Guangxi mainly belong to Begoniasect.Coelocentrum Irmscher. In this article, we described and illustrated a new species in sect. Platycentrum (Klotzsch) A.DC., Begoniaparvibracteata X.X.Feng, R.K.Li & Z.X.Liu, which was discovered in a karst forest of south-western Guangxi. The begonia shows high morphological similarity to B.subhowii S.H. Huang and B.psilophylla Irmscher, but differs from the latter two in its narrower oblique-ovate asymmetric leaf blade, 4 (occasionally 6) tepals of pistillate flower and smaller membranous inflorescence bracts. Molecular phylogenetic analysis, based on ITS sequence data, supports the new species as monophyletic and distinct from B.subhowii and B.psilophylla. Considering its narrow distribution and the disturbance of human activities, the conservation status of new taxon is evaluated as "Vulnerable" (VU B1, B2 ab (i, iv, v), D2) according to the IUCN Red List Categories and Criteria.