The divalent metal ion exporter IhpABC is required to maintain iron homeostasis under low to moderate environmental iron conditions in the bacterium Bradyrhizobium japonicum.

Bacterial iron export mitigates high iron stress, but a role for it under lower iron conditions has not been established. MbfA is the high iron stress exporter in Bradyrhizobium japonicum. Here, we identify the ihpABC genes in a selection for secondary site mutations that suppress the poor growth phenotype of feoAB mutants defective in iron acquisition. IhpABC belongs to the RND tripartite efflux pump family. High iron conditions that derepress the mbfA gene partially rescued the growth of an ihpC mutant but reverted the feoB ihpC mutant to the feoB growth phenotype. The ihpA mutant grown under low iron conditions accumulated higher levels of iron compared to the wild type, and it displayed aberrant iron-responsive gene expression. The mbfA mutant was more sensitive than the wild type to H2 O2 , but the ihpA mutant was not sensitive. The ihpA mutant accumulated more Zn, Co and Cd than was found in the wild type, and growth of the mutant was more sensitive to inhibition by ZnCl2 , CoCl2 and CdCl2 . The findings suggest that IhpABC is a divalent metal ion exporter that helps maintain iron homeostasis under low to moderate environmental iron levels. Thus, iron export is not limited to managing high iron stress.

Parallel-Forms Reliability and Minimal Detectable Change of the Four Telerehabilitation Version Mobility-Related Function Scales in Stroke Survivors.

OBJECTIVE: To investigate the parallel-forms reliability, minimal detectable change with 95% confidence interval (MDC95), and feasibility of the 4 telerehabilitation version mobility-related function scales: Fugl-Meyer Assessment-lower extremity subscale (Tele-FMA-LE), Berg Balance Scale (Tele-BBS), Tinetti Performance Oriented Mobility Assessment-Gait subscale (Tele-POMA-G), and Rivermead Mobility Index (Tele-RMI). DESIGN: Reliability and agreement study and cross-sectional study. SETTING: Medical center. PARTICIPANTS: Stroke survivors' ability to independently walk 3 meters with assistive devices, age of ≥18 years for participants and their partners, stable physical condition, and absence of cognitive impairment (N=60). INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Parallel-forms reliability and MDC95 of Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI. RESULTS: No significant differences (P>.05) were observed among the mean scores of the telerehabilitation version and face-to-face version mobility-related function scales. Intraclass correlation coefficients (ICCs) indicated good reliability for most scales, with Tele-FMA-LE, Tele-BBS, and Tele-RMI scores achieving values of 0.81, 0.78, and 0.84. Tele-POMA-G scores demonstrated moderate reliability (ICC=0.72). Weighted kappa (κw) showed good-to-excellent reliability for most individual items (κw>0.60). The MDCs of the Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI were 5.84, 8.10, 2.74, and 1.31, respectively. Bland-Altman analysis showed adequate agreement between tele-assessment and face-to-face assessment for all scales. The 5 dimensions affirm the robust feasibility of tele-assessment: assessment time, subjective fatigue perception, overall preference, participant satisfaction, and system usability. CONCLUSIONS: The study demonstrates good parallel-forms reliability, MDC, and promising feasibility of the 4 telerehabilitation version mobility-related function scales (Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI) in survivors of stroke.

Detect the early-warning signals of diseases based on signaling pathway perturbations on a single sample.

BACKGROUND: During the pathogenesisof complex diseases, a sudden health deterioration will occur as results of the cumulative effect of various internal or external factors. The prediction of an early warning signal (pre-disease state) before such deterioration is very important in clinical practice, especially for a single sample. The single-sample landscape entropy (SLE) was proposed to tackle this issue. However, the PPI used in SLE was lack of definite biological meanings. Besides, the calculation of multiple correlations based on limited reference samples in SLE is time-consuming and suspect. RESULTS: Abnormal signals generally exert their effect through the static definite biological functions in signaling pathways across the development of diseases. Thus, it is a natural way to study the propagation of the early-warning signals based on the signaling pathways in the KEGG database. In this paper, we propose a signaling perturbation method named SSP, to study the early-warning signal in signaling pathways for single dynamic time-series data. Results in three real datasets including the influenza virus infection, lung adenocarcinoma, and acute lung injury show that the proposed SSP outperformed the SLE. Moreover, the early-warning signal can be detected by one important signaling pathway PI3K-Akt. CONCLUSIONS: These results all indicate that the static model in pathways could simplify the detection of the early-warning signals.

A cuproptosis random forest cox score model-based evaluation of prognosis, mutation characterization, immune infiltration, and drug sensitivity in hepatocellular carcinoma.

Background: Hepatocellular carcinoma is the third most deadly malignant tumor in the world with a poor prognosis. Although immunotherapy represents a promising therapeutic approach for HCC, the overall response rate of HCC patients to immunotherapy is less than 30%. Therefore, it is of great significance to explore prognostic factors and investigate the associated tumor immune microenvironment features. Methods: By analyzing RNA-seq data of the TCGA-LIHC cohort, the set of cuproptosis related genes was extracted via correlation analysis as a generalization feature. Then, a random forest cox prognostic model was constructed and the cuproptosis random forest cox score was built by random forest feature filtering and univariate multivariate cox regression analysis. Subsequently, the prognosis prediction of CRFCS was evaluated via analyzing data of independent cohorts from GEO and ICGC by using KM and ROC methods. Moreover, mutation characterization, immune cell infiltration, immune evasion, and drug sensitivity of CRFCS in HCC were assessed. Results: A cuproptosis random forest cox score was built based on a generalization feature of four cuproptosis related genes. Patients in the high CRFCS group exhibited a lower overall survival. Univariate multivariate Cox regression analysis validated CRFCS as an independent prognostic indicator. ROC analysis revealed that CRFCS was a good predictor of HCC (AUC =0.82). Mutation analysis manifested that microsatellite instability (MSI) was significantly increased in the high CRFCS group. Meanwhile, tumor microenvironment analysis showed that the high CRFCS group displayed much more immune cell infiltration compared with the low CRFCS group. The immune escape assessment analysis demonstrated that the high CRFCS group displayed a decreased TIDE score indicating a lower immune escape probability in the high CRFCS group compared with the low CRFCS group. Interestingly, immune checkpoints were highly expressed in the high CRFCS group. Drug sensitivity analysis revealed that HCC patients from the high CRFCS group had a lower IC50 of sorafenib than that from the low CRFCS group. Conclusions: In this study, we constructed a cuproptosis random forest cox score (CRFCS) model. CRFCS was revealed to be a potential independent prognostic indicator of HCC and high CRFCS samples showed a poor prognosis. Interestingly, CRFCS were correlated with TME characteristics as well as clinical treatment efficacy. Importantly, compared with the low CRFCS group, the high CRFCS group may benefit from immunotherapy and sorafenib treatment.

PmiRtarbase: A positive miRNA-target regulations database.

MicroRNAs (miRNAs) are ~22 nt small non-coding RNA segments that are widely involved in the regulation of gene expression. Accumulating evidences show that miRNAs not only inhibit the expression of some targeted genes but also promote that of some targeted genes in specific conditions. Over the past decades, many miRNA-target databases have been developed from computational prediction and/or experimental validation perspectives. However, there is no database available to systematically collect positive miRNA-target associations that are essential in deciphering the miRNA regulation mechanism. To promote the miRNA study, we developed a new database: PmiRtarbase that acquires validated positive miRNA-target interactions by mining published literature. It includes 312 curated associations between 119 miRNAs and 169 genes in 8 species from 130 studies and summarizes the conditions and detailed descriptions of the miRNA-target associations. We also constructed a database named PmiRtarbase, a user-friendly interface to conveniently search and download all related entries. This elaborate database aims to serve as a beneficial resource for studying the miRNA positive regulation mechanism and miRNA-based therapeutics. DATA AVAILABILITY: The full positive miRNA-target data can be accessed through the link http://www.lwb-lab.cn/PmiRtarbase. Users of this dataset should acknowledge the contributions of the original authors and properly cite this article.

A simple pre-disease state prediction method based on variations of gene vector features.

BACKGROUND: The progression of disease can be divided into three states: normal, pre-disease, and disease. Since a pre-disease state is the tipping point of disease deterioration, accurately predicting pre-disease state may help to prevent the progression of disease and develop feasible treatment in time. METHODS: In the perspective of gene regulatory network, the expression of a gene is regulated by its upstream genes, and then it also regulates that of its downstream genes. In this study, we define the expression value of these genes as a gene vector to depict its state in a specific sample. Then, we propose a novel pre-disease prediction method by such vector features. RESULTS: The results of an influenza virus infection dataset show that our method can successfully predict the pre-disease state. Furthermore, the pre-disease state related genes predicted by our methods are highly associated with each other and enriched in influenza virus infection related pathways. In addition, our method is more time efficient in calculation than previous works. The code of our method is accessed at https://github.com/ZhenshenBao/sPGVF.git.

ROC Curve Analysis of Electrophysiological Monitoring and Early Warning During Intracranial Aneurysm Clipping.

OBJECTIVE: To explore the safe duration of temporary clipping of the parent artery under intraoperative electrophysiological monitoring. METHODS: The clinical data of 97 patients who underwent intracranial aneurysm clipping under electrophysiological monitoring in the Department of Neurology, Affiliated Hospital of Qingdao University from June 2019 to June 2020 were retrospectively analyzed. The safety duration of temporary clipping was analyzed using receiver operating characteristic (ROC) curves, and the results were validated in clinical data. RESULTS: Temporary clipping during operation (P < 0.05) and electrophysiological warning during operation (P < 0.05) were related risk factors of a cerebral ischemia event after operation. The ROC curve was drawn for the duration of temporary clipping and the occurrence of intraoperative electrophysiological warning, and the area under the curve was 0.78 (P < 0.05). The optimal cutoff value was 372.5 seconds, the sensitivity was 0.818, and the specificity was 0.762. After reviewing the clinical data, P < 0.05 was statistically significant after a χ2 test with 372.5 seconds equal to approximately 6 minutes. The ROC curve was drawn for the duration of temporary clipping and the time of postoperative ischemia, and the area under the curve was 0.667 (P < 0.05). The optimal cutoff value was 430.5 seconds, the sensitivity was 0.592, and the specificity was 0.842. CONCLUSION: Temporary intraoperative block is the risk factor for cerebral ischemia after operation. In this study, the temporary clipping time of the parent artery should not be longer than 6 minutes, and there is approximately 1 minute to adjust the current procedure after the electrophysiological warning to restore the baseline of intraoperative electrophysiological monitoring.

Pathological Changes in Surgically Resected Cystic Cerebral Cavernous Malformation 13 Years After Radiosurgery: Case Report and Review of the Literature.

BACKGROUND: Stereotactic radiosurgery (SRS) as a treatment for cerebral cavernous malformation (CCM) has been controversial, but there are few pathological reports showing its long-term therapeutic effect, and literature reporting the CCM cyst formation after SRS is also rare. CASE DESCRIPTION: We present a 30-year-old woman with a ruptured right parietal CCM treated with SRS 13 years ago. The post-SRS imaging follow-up revealed CCM rehemorrhage and cyst formation. Surgical resection was performed, and a subsequent pathological examination revealed that the CCM still had some incomplete occluded vessels and a large number of newly formed capillaries, and hemorrhagic band and hemosiderin were seen around the nodule. CONCLUSIONS: Recurrent hemorrhage after SRS for CCM could be related to incomplete occluded vessels and newly formed capillaries. Repeated hemorrhage from CCM newly formed capillaries into the small cavity increased the osmotic pressure, resulting in fluid entering the cavity and cyst enlargement.

Catalyst System for Hydrogenation Catalysis Based on Multiarm Hyperbranched Polymer Templated Metal (Au, Pt, Pd, Cu) Nanoparticles.

With a hyperbranched poly(amidoamine) core and many water-soluble poly(ethylene glycol) monomethyl ether arms connected by pH-sensitive acylhydrazone bonds, multiarm hyperbranched polymer was used as nanoreactor and reductant to prepare metal nanoparticles endowed with intelligence and biocompatibility. The multiarm hyperbranched polymer encapsulated nanoparticles (NPs) showed excellent catalytic activity for hydrogenation, thus an excellent catalyst system for hydrogenation was established. The rate constants could reach as high as 3.48 L·s-1·m-2, which can be attributed to the lack of surface passivation afforded by the multiarm hyperbranched polymer.

DNA computation model to solve 0-1 programming problem.

0-1 programming problem is an important problem in opsearch with very widespread applications. In this paper, a new DNA computation model utilizing solution-based and surface-based methods is presented to solve the 0-1 programming problem. This model contains the major benefits of both solution-based and surface-based methods; including vast parallelism, extraordinary information density and ease of operation. The result, verified by biological experimentation, revealed the potential of DNA computation in solving complex programming problem.

A Chinese Postman Problem based on DNA computing.

DNA computing is a novel method for solving a class of intractable computational problems, in which the computing can grow exponentially with the problem size. Up to now, many accomplishments have been achieved to improve its performance and increase its reliability. A Chinese Postman Problem has been solved by means of molecular biology techniques in the paper. A small graph was encoded in molecules of DNA, and the "operations" of the computation were performed with standard protocols and enzymes. This work represents further evidence for the ability of DNA computing to solve NP-complete search problems.

A DNA algorithm for the graph coloring problem.

A DNA algorithm based on surfaces for the graph coloring problem is presented. First the whole combinatorial color assignments to the vertices of a graph are synthesized and immobilized on a surface; then a vertex is legally colored while those adjacent to it with illegal colors are deleted; and the cycle is repeated until finally the correct color assignments to the graph are reached. Compared with the other DNA algorithms, our algorithm is easy to implement and error-resistant.

DNA sequence design based on template strategy.

In DNA based computation and DNA nanotechnology, the design of proper DNA sequences has turned out to be an elementary problem. This paper takes a further look at the template strategy proposed in work by Frutos, A. G. et al. (Nucleic Acids Res. 1997, 25, 4748-4757). The H-measure proposed by Garzon et al. (Proceedings of the Second Annual Genetic Programming Conference, 1997; pp 472-487) is combined in this strategy to optimize the template and map sets obtained. Finally we describe a constructing method that can still produce more sequences by the results obtained in this paper.