Hidden blood loss and its influencing factors after cement augmentation for vertebral metastasis.

Introduction: Few studies have focused on the risk factors for hidden blood loss (HBL) during cement augmentation surgery for pathologic vertebral compression fraction (PVCFs). Method: From January 2014 to December 2020, the clinical data of 169 PVCF patients (283 levels) who underwent cement augmentation were retrospectively analysed. HBL was calculated according to the linear Gross formula using the patient's average Hct during the perioperative course and PBV. Multivariate linear regression analysis was performed to evaluate the independent factors associated with HBL. Results: The mean HBL was 448.2 ± 267.2 ml, corresponding to 10.8% ± 6.2% of the patient blood volume (PBV). There were significant differences between pre- and postoperative haematocrit (Hct) (P < 0.001) and Hb (P < 0.001), and 132 patients developed anaemia postoperatively, while 79 patients had anaemia preoperatively (P < 0.001). Multivariate linear regression revealed that bone lesion quality (p = 0.028), number of PVCFs (p = 0.002), amount of bone cement (p = 0.027), bone cement leakage (p = 0.001), and percentage of vertebral height loss (VHL) (p = 0.011) were independent risk factors for HBL. Conclusion: In conclusion, patients with lytic vertebral destruction, larger amounts of bone cement, greater amounts of bone cement leakage, more PVCF(s), and greater percentages of VHL may be more prone to HBL.

Structural bioinformatics studies of six human ABC transporters and their AlphaFold2-predicted water-soluble QTY variants.

Human ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins and perform diverse functions. Many of them are associated with multidrug resistance that often results in cancer treatment with poor outcomes. Here, we present the structural bioinformatics study of six human ABC membrane transporters with experimentally determined cryo-electron microscopy (CryoEM) structures including ABCB7, ABCC8, ABCD1, ABCD4, ABCG1, ABCG5, and their AlphaFold2-predicted water-soluble QTY variants. In the native structures, there are hydrophobic amino acids such as leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in the transmembrane alpha helices. These hydrophobic amino acids are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y). Therefore, these QTY variants become water soluble. We also present the superposed structures of native ABC transporters and their water-soluble QTY variants. The superposed structures show remarkable similarity with root mean square deviations between 1.064 and 3.413 Å despite significant (41.90-54.33%) changes to the protein sequence of the transmembrane domains. We also show the differences in hydrophobicity patches between the native ABC transporters and their QTY variants. We explain the rationale behind why the QTY membrane protein variants become water soluble. Our structural bioinformatics studies provide insight into the differences between the hydrophobic helices and hydrophilic helices and will likely further stimulate designs of water-soluble multispan transmembrane proteins and other aggregated proteins. The water-soluble ABC transporters may be useful as soluble antigens to generate therapeutic monoclonal antibodies for combating multidrug resistance in clinics.

Structural bioinformatics studies of glutamate transporters and their AlphaFold2 predicted water-soluble QTY variants and uncovering the natural mutations of L->Q, I->T, F->Y and Q->L, T->I and Y->F.

Glutamate transporters play key roles in nervous physiology by modulating excitatory neurotransmitter levels, when malfunctioning, involving in a wide range of neurological and physiological disorders. However, integral transmembrane proteins including the glutamate transporters remain notoriously difficult to study, due to their localization within the cell membrane. Here we present the structural bioinformatics studies of glutamate transporters and their water-soluble variants generated through QTY-code, a protein design strategy based on systematic amino acid substitutions. These include 2 structures determined by X-ray crystallography, cryo-EM, and 6 predicted by AlphaFold2, and their predicted water-soluble QTY variants. In the native structures of glutamate transporters, transmembrane helices contain hydrophobic amino acids such as leucine (L), isoleucine (I), and phenylalanine (F). To design water-soluble variants, these hydrophobic amino acids are systematically replaced by hydrophilic amino acids, namely glutamine (Q), threonine (T) and tyrosine (Y). The QTY variants exhibited water-solubility, with four having identical isoelectric focusing points (pI) and the other four having very similar pI. We present the superposed structures of the native glutamate transporters and their water-soluble QTY variants. The superposed structures displayed remarkable similarity with RMSD 0.528Å-2.456Å, despite significant protein transmembrane sequence differences (41.1%->53.8%). Additionally, we examined the differences of hydrophobicity patches between the native glutamate transporters and their QTY variants. Upon closer inspection, we discovered multiple natural variations of L->Q, I->T, F->Y and Q->L, T->I, Y->F in these transporters. Some of these natural variations were benign and the remaining were reported in specific neurological disorders. We further investigated the characteristics of hydrophobic to hydrophilic substitutions in glutamate transporters, utilizing variant analysis and evolutionary profiling. Our structural bioinformatics studies not only provided insight into the differences between the hydrophobic helices and hydrophilic helices in the glutamate transporters, but they are also expected to stimulate further study of other water-soluble transmembrane proteins.

Discovery of Dehydroabietylamine Derivatives as Antibacterial and Antifungal Agents.

A diverse array of biologically active derivatives was derived by modifying the chemically active sites of dehydroabietylamine. Herein, we describe the synthesis of a new series of C-19-arylated dehydroabietylamine derivatives using a palladium-catalyzed C(sp3)-H activation reaction. Five analogues (3b, 3d, 3h, 3n, and 4a) exhibited antibacterial activity against Escherichia coli. Compound 4a exhibited strong inhibitory activity against DNA Topo II and Topo IV. Molecular docking modeling indicated that it can bind effectively to the target through interactions with amino acid residues. The synthesized compounds were tested in vitro for their antifungal activity against six common phytopathogenic fungi. The mechanism of action of compound 4c against Rhizoctorzia solani was investigated, revealing that it disrupts the morphology of the mycelium and enhances cell membrane permeability.

Structural bioinformatics studies of serotonin, dopamine and norepinephrine transporters and their AlphaFold2 predicted water-soluble QTY variants and uncovering the natural mutations of L->Q, I->T, F->Y and Q->L, T->I and Y->F.

Monoamine transporters including transporters for serotonin, dopamine, and norepinephrine play key roles in monoaminergic synaptic signaling, involving in the molecular etiology of a wide range of neurological and physiological disorders. Despite being crucial drug targets, the study of transmembrane proteins remains challenging due to their localization within the cell membrane. To address this, we present the structural bioinformatics studies of 7 monoamine transporters and their water-soluble variants designed using the QTY code, by systematically replacing the hydrophobic amino acids leucine (L), valine (V), isoleucine (I) and phenylalanine (F) with hydrophilic amino acids (glutamine (Q), threonine (T) and tyrosine (Y). The resulting QTY variants, despite significant protein transmembrane sequence differences (44.27%-51.85%), showed similar isoelectric points (pI) and molecular weights. While their hydrophobic surfaces significantly reduced, this change resulted in a minimal structural alteration. Quantitatively, Alphafold2 predicted QTY variant structures displayed remarkable similarity with RMSD 0.492Å-1.619Å. Accompanied by the structural similarities of substituted amino acids in the context of 1.5Å electron density maps, our study revealed multiple QTY and reverse QTY variations in genomic databases. We further analyzed their phenotypical and topological characteristics. By extending evolutionary game theory to the molecular foundations of biology, we provided insights into the evolutionary dynamics of chemically distinct alpha-helices, their usage in different chemotherapeutic applications, and open possibilities of diagnostic medicine. Our study rationalizes that QTY variants of monoamine transporters may not only become distinct tools for medical, structural, and evolutionary research, but these transporters may also emerge as contemporary therapeutic targets, providing a new approach to treatment for several conditions.

Screening and verification of hub genes in esophageal squamous cell carcinoma by integrated analysis.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. However, the mechanisms underlying ESCC tumorigenesis have not been fully elucidated. Thus, we aimed to determine the key genes involved in ESCC tumorigenesis. The following bioinformatics analyses were performed: identification of differentially expressed genes (DEGs); gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis; integrated analysis of the protein-protein interaction network and Gene Expression Profiling Interactive Analysis database for validation of hub genes. Finally, western blotting and qPCR were used to explore the expression of cell division cycle 6 (CDC6) in ESCC cell lines. Immunohistochemistry analysis of ESCC samples from patients and matched clinical characteristics was used to determine the effects of CDC6. A total of 494 DEGs were identified, and functional enrichment was mainly focused on cell cycle and DNA replication. Biological pathway analysis of the hub genes was closely related to the cell cycle. We found that CDC6 was upregulated in ESCC cell lines and patient tissues and was related to the clinicopathological characteristics of ESCC. In conclusion, this study identified hub genes and crucial biological pathways related to ESCC tumorigenesis and integrated analyses indicated that CDC6 may be a novel diagnostic and therapeutic target for ESCC.

The clinical value of ß-D-glucan testing and next-generation metagenomic sequencing for the diagnosis of fungal endophthalmitis.

PURPOSE: To explore the clinical value of ß-D-glucan (BDG) testing and next-generation metagenomic sequencing (mNGS) for detecting the pathogens of fungal endophthalmitis (FE). METHODS: This study included 32 cases (32 eyes) with FE and 20 cases (20 eyes) with intraocular inflammation caused by other etiologies. All patients underwent extraction of aqueous humor or vitreous fluid samples for BDG testing and mNGS. The diagnostic performance and total clinical concordance rate (TCCR) of BDG testing and mNGS for FE were evaluated and calculated based on the results of the clinical diagnosis. RESULTS: Among the clinically diagnosed FE, the positivity rates of BDG testing and mNGS (90.63%) were both significantly higher (P<0.001) than that of microbial cultures (53.13%). There was 100% consistency in pathogen identification using mNGS and culture identification for culture-positive cases. The area under the curve (AUC) was 0.927 for BDG testing and 0.853 for mNGS. When the 2 tests were combined, the sensitivity (93.75%), specificity (100.00%), and TCCR (96.15%) were all improved compared with the single tests. CONCLUSIONS: The positive rates of BDG test and mNGS were markedly higher than those of cultures in FE identification. The combination of these 2 tests showed improved performance when compared with individual tests.

Inhibitory effect of truncated isoforms on GPCR dimerization predicted by combinatorial computational strategy.

G protein-coupled receptors (GPCRs) play a pivotal role in fundamental biological processes and disease development. GPCR isoforms, derived from alternative splicing, can exhibit distinct signaling patterns. Some highly-truncated isoforms can impact functional performance of full-length receptors, suggesting their intriguing regulatory roles. However, how these truncated isoforms interact with full-length counterparts remains largely unexplored. Here, we computationally investigated the interaction patterns of three human GPCRs from three different classes, ADORA1 (Class A), mGlu2 (Class C) and SMO (Class F) with their respective truncated isoforms because their homodimer structures have been experimentally determined, and they have truncated isoforms deposited and identified at protein level in Uniprot database. Combining the neural network-based AlphaFold2 and two physics-based protein-protein docking tools, we generated multiple complex structures and assessed the binding affinity in the context of atomistic molecular dynamics simulations. Our computational results suggested all the four studied truncated isoforms showed potent binding to their counterparts and overlapping interfaces with homodimers, indicating their strong potential to block homodimerization of their counterparts. Our study offers insights into functional significance of GPCR truncated isoforms and supports the ubiquity of their regulatory roles.

A Rapid and Sensitive Gold Nanoparticle-Based Lateral Flow Immunoassay for Chlorantraniliprole in Agricultural and Environmental Samples.

Chlorantraniliprole (CAP) is a new type of diamide insecticide that is mainly used to control lepidopteran pests. However, it has been proven to be hazardous to nontarget organisms, and the effects of its residues need to be monitored. In this study, five hybridoma cell lines were developed that produced anti-CAP monoclonal antibodies (mAbs), of which the mAb originating from the cell line 5C5B9 showed the highest sensitivity and was used to develop a gold nanoparticle-based lateral flow immunoassay (AuNP-LFIA) for CAP. The visible limit of detection of the AuNP-LFIA was 1.25 ng/mL, and the detection results were obtained in less than 10 min. The AuNP-LFIA showed no cross-reactivity for CAP analogs, except for tetraniliprole (50%) and cyclaniliprole (5%). In the detection of spiked and blind samples, the accuracy and reliability of the AuNP-LFIA were confirmed by a comparison with spiked concentrations and verified by ultra-performance liquid chromatography-tandem mass spectrometry. Thus, this study provides the core reagents for establishing CAP immunoassays and a AuNP-LFIA for the detection of residual CAP.

A Modification of the American Joint Committee on Cancer Nomogram for Undifferentiated Sarcoma With External Validation and Risk Stratification.

BACKGROUND: The aim of this study is to establish a model to predict the overall survival (OS) and stratify the risk of postoperative patients with undifferentiated sarcoma. METHODS: A total of 452 postoperative patients with undifferentiated sarcoma in the trunk and extremity from the Surveillance, Epidemiology, and End Results database were enrolled as the training cohort. We collected a group of 163 undifferentiated sarcoma patients from our center as the external validation cohort. Cox proportional hazards regression model was used to screen survival-associated factors for the construction of the nomogram. Concordance-indexes (C-indexes), calibration curves, and receiver operating characteristics (ROCs) curves were applied for the discrimination and calibration of the nomogram. The cutoff value of nomogram-based total points was applied to stratify the risk of patients. RESULTS: A nomogram was developed incorporating four independent factors: age, tumor site, eighth AJCC stage, and radiotherapy. The nomogram showed good prognostic accuracy and excellent agreement in the training and validation cohort, with C-indexes of .701 (95% confidence interval [CI]: .683-.719) and .700 (95% CI: 0.659-.741), respectively. Furthermore, we identified the best cutoff value of nomogram total points (103.2) as the predicted risk and divided the patients into a high-risk group and a low-risk group. Significant differences in OS between the two groups were indicated in the training cohort and external validation cohort, showing the appreciable clinical validity and clinical utility of the nomogram (P < .001). CONCLUSION: This nomogram provides an insightful and applicable tool for individual evaluations and the distinguishment of risk for patients with undifferentiated sarcoma.

Clinical application of ultrasound-guided totally implantable venous access ports implantation via the posterior approach of the internal jugular vein.

BACKGROUND: To determine the feasibility and safety of ultrasound-guided totally implantable venous access port (TIVAP) implantation via the posterior approach of the internal jugular vein (IJV). METHODS: From September 2021 to August 2022, 88 oncology patients underwent ultrasound-guided implantation of TIVAPs via the posterior approach of the IJV for the administration of chemotherapy. The catheter tip was adjusted to be positioned at the cavoatrial junction under fluoroscopic guidance. Clinical data including surgical success, success rate for the first attempt, intraoperative, and postoperative complications were all collected and analyzed. RESULTS: All patients underwent successful surgery (100%), whereby 58 were via the right IJV and 30 via the left IJV, and the success rate for the first attempt was 96.59% (85/88). The operation time was 20 to 43 minutes, with an average of 26.59 ± 6.18 minutes with no intraoperative complications. The follow-up duration ranged from 1 to 12 months (mean = 5.28 ± 3.07) and the follow-up rate was 100%. The rate of postoperative complications was 4.55% (4/88), including port-site infection in two cases, fibrin sheath formation in one case, and port flip in one case. No other complications were observed during follow-up. CONCLUSION: Ultrasound-guided TIVAP implantation via the posterior approach of the IJV is feasible, safe, and effective, with a low rate of intraoperative and postoperative complications. Not only was the curvature of the catheter device smooth, but patients were satisfied with the comfort and cosmetic appearance. Additionally, we could reduce the possible complications of pinching and kinking of the catheter by using this approach. Therefore, further large-sample, prospective, and randomized controlled trials are warranted.

QTY code designed antibodies for aggregation prevention: A structural bioinformatic and computational study.

Therapeutic monoclonal antibodies are the most rapidly growing class of molecular medicine, and they are beneficial to the treatment of a broad spectrum of human diseases. However, the aggregation of antibodies during the process of manufacture, distribution, and storage poses significant challenges, potentially compromising efficacy and inducing adverse immune responses. We previously conceived a QTY (glutamine, threonine, tyrosine) code, a simple tool for enhancing protein water-solubility by systematically pairwise replacing hydrophobic residues L (leucine), V (valine)/I (isoleucine), and F (phenylalanine). The QTY code offers a promising alternative to traditional methods of controlling aggregation in integral transmembrane proteins. In this study, we designed variants of four antibodies applying the QTY code, changing only the ß-sheets. Through the structure-based aggregation analysis, we found that these QTY antibody variants demonstrated significantly decreased aggregation propensity compared to their wild-type counter parts. Our results of molecular dynamics simulations showed that the design by QTY code is capable of maintaining the antigen-binding affinity and structural stability. Our structural informatic and computational study suggests that the QTY code offers a significant potential in mitigating antibody aggregation.

A comprehensive two-sample Mendelian randomization analysis of trigeminal neuralgia and modifiable risk factors.

Objective: To conduct a comprehensive search and causality study of potential modifiable risk factors for trigeminal neuralgia. To provide new ideas for subsequent treatment and management of patients with trigeminal neuralgia. Methods: Data were obtained from large GWAS databases and then analyzed by Mendelian randomization analysis. The causal relationship between 36 potentially modifiable risk factors and trigeminal neuralgia was explored based on the results of the inverse variance weighting method(IVW). p < 0.05 was considered statistically significant. Results: Years of schooling [OR (95%CI), 0.59(0.42-0.84), p = 0.003] to be a significant protective factor. Anxiety disorders [OR (95%CI), 1.62(1.05-2.48), p = 0.028], Depression [OR (95%CI), 1.53(1.03-2.28), p = 0.035] and Autoimmune [OR (95%CI), 1.16(1.01-1.32), p = 0.033] were significant risk factors. Sleep duration [OR (95%CI), 0.43(0.18-1.01), p = 0.051] was a close protective factor. Body mass index [OR (95%CI), 1.24(0.98-1.57), p = 0.077] was a close risk factor. Conclusion: Mendelian randomization analysis shows Years of schooling and Sleep duration as protective factors. Anxiety disorders, Depression, Autoimmune, and Body mass index are risk factors. This will help in the research of diagnosis, treatment, and mechanism of trigeminal neuralgia. And reduce the prevalence of trigeminal neuralgia through positive psychological and lifestyle interventions.

Trigeminal neuralgia associated with dural arteriovenous fistula: a case report and literature reviews.

Trigeminal neuralgia is a paroxysmal, intense electric shock-like, or knife-like, recurrent pain that affects one or more sense areas of the unilateral facial trigeminal nerve. It can be classified into two groups from an etiological standpoint: primary and secondary. The pain episodes brought on by such vascular compression are still categorized as primary trigeminal neuralgia, despite the fact that microvascular compression of the trigeminal nerve root has now been demonstrated to be the primary cause. A rare and complicated condition known as a dural arteriovenous fistula (DAVF) can irritate the Gasserian ganglion or compress the trigeminal nerve's root entry zone (REZ), leading to secondary trigeminal neuralgia (TN). At present, the treatment of DAVF-induced trigeminal neuralgia is not conclusive. This article reports a case of DAVF-induced trigeminal neuralgia cured by MVD and reviews the relevant literature.

Enhanced Anticoagulation of Hierarchy Liquid Infused Surfaces in Blood Flow.

Liquid infused surfaces (LIS) hold remarkable potential in anticoagulation. However, liquid loss of LIS in the bloodstream remains a challenge toward its clinical application. Here, micronano hierarchy structures are obtained on the titanium alloy substrate by regulating the microspheres' distribution. When the gap between the microspheres is smaller than the diameter of the red blood cell (RBC), the LIS is more stable under the blood wash and presents a better anticoagulation performance. The proper interval is found to prevent the RBCs from entering the gap and remove the liquid on the surface. The retained thickness of the liquid film is measured by the atomic force microscopy (AFM) technique. The LIS is applied on the front guide vane of an artificial heart pump and exhibits significant improvement on anticoagulation in the blood circulation in vitro for 25 h. The techniques and findings can be used to optimize the anticoagulation performance of LIS-related biomedical implant devices.

Dynamic Dimerization of Chemokine Receptors and Potential Inhibitory Role of Their Truncated Isoforms Revealed through Combinatorial Prediction.

Chemokine receptors play crucial roles in fundamental biological processes. Their malfunction may result in many diseases, including cancer, autoimmune diseases, and HIV. The oligomerization of chemokine receptors holds significant functional implications that directly affect their signaling patterns and pharmacological responses. However, the oligomerization patterns of many chemokine receptors remain poorly understood. Furthermore, several chemokine receptors have highly truncated isoforms whose functional role is not yet clear. Here, we computationally show homo- and heterodimerization patterns of four human chemokine receptors, namely CXCR2, CXCR7, CCR2, and CCR7, along with their interaction patterns with their respective truncated isoforms. By combining the neural network-based AlphaFold2 and physics-based protein-protein docking tool ClusPro, we predicted 15 groups of complex structures and assessed the binding affinities in the context of atomistic molecular dynamics simulations. Our results are in agreement with previous experimental observations and support the dynamic and diverse nature of chemokine receptor dimerization, suggesting possible patterns of higher-order oligomerization. Additionally, we uncover the strong potential of truncated isoforms to block homo- and heterodimerization of chemokine receptors, also in a dynamic manner. Our study provides insights into the dimerization patterns of chemokine receptors and the functional significance of their truncated isoforms.

Effect of shaking manners on floral aroma quality and identification of key floral-aroma-active compounds in Hunan black tea.

Shaking is a key process effecting the floral aroma of Hunan black tea (HBT). In this study, the aroma composition of HBTs shaken in the early withering stage (ES1, ES1 + LS1, and ES2), shaken in the late withering stage (LS1), and not shaken (NS), and the identification of main floral aroma compounds were analyzed using sensory evaluation combined with gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), and aroma recombination experiments. Sensory evaluation results showed that the floral aroma of HBT shaken in the early withering stage was with high intensity, whereas HBT shaken in the late withering stage had low-intensity floral aroma. GC-MS identified a total number of 81 differential volatile compounds in HBT, including 30 esters, 18 aldehydes, 15 alcohols, 12 terpenes, 4 ketones, and 2 nitrogen-containing compounds. Further screening of important floral aroma differential compounds was performed using sensory-guided, odor activity value (OAV), and GC-O analysis, which identified three critical floral aroma differential compounds. Eventually, absolute quantification analysis and aroma recombination experiments confirmed that indole and methyl jasmonate were the most critical compounds of HBT determining floral aroma intensity. The findings of this study provide valuable guidance for the production of HBT with rich floral aroma attributes.

Tripartite motif containing 26 prevents steatohepatitis progression by suppressing C/EBPδ signalling activation.

Currently potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) and NASH-related pathopoiesis have failed to achieve expected therapeutic efficacy due to the complexity of the pathogenic mechanisms. Here we show Tripartite motif containing 26 (TRIM26) as a critical endogenous suppressor of CCAAT/enhancer binding protein delta (C/EBPδ), and we also confirm that TRIM26 is an C/EBPδ-interacting partner protein that catalyses the ubiquitination degradation of C/EBPδ in hepatocytes. Hepatocyte-specific loss of Trim26 disrupts liver metabolic homeostasis, followed by glucose metabolic disorder, lipid accumulation, increased hepatic inflammation, and fibrosis, and dramatically facilitates NASH-related phenotype progression. Inversely, transgenic Trim26 overexpression attenuates the NASH-associated phenotype in a rodent or rabbit model. We provide mechanistic evidence that, in response to metabolic insults, TRIM26 directly interacts with C/EBPδ and promotes its ubiquitin proteasome degradation. Taken together, our present findings identify TRIM26 as a key suppressor over the course of NASH development.

Analysis on coupling dynamic effect of human errors in aviation safety.

Human factors have increasingly been the leading cause of aircraft accidents. In most cases, human factors are not working alone, instead they are coupled with complex environment, mechanical factors, physiological and psychological factors of pilots, and organizational management, all of which form a complex aviation safety system. It is vital to investigate the coupling impact of human errors to avoid the occurrence of aviation accidents. In view that the Human Factors Analysis and Classification System (HFACS) provides a hierarchical classification principle of human errors in aviation accidents, and the System Dynamics (SD) approach is helpful to describe the risk evolution process, this paper establishes a hybrid HFACS-SD model by employing the HFACS and the SD approach to reveal the aviation human factors risk evolution mechanism, in which the HFACS is first used to capture the causal factors of human errors risk, and a coupling SD model is then built to describe the evolution of aviation human factors risk supported by historical data. The eigenvalue elasticity analysis is taken to identify critical loops and parameters that have a substantial impact on the system structural behavior, and the influence of parameters and loops is assessed. Simulation results show that the evolution trend of the accident rate can be replicated by the proposed HFACS-SD model, and the structural dominance analysis can efficiently identify critical loops and parameters. Simulation results further show that, with the recommended safety enhancement measures, the stability of the aviation system is increased, and thus lowering the overall accident rate.

CrMP-Sol database: classification, bioinformatic analyses and comparison of cancer-related membrane proteins and their water-soluble variant designs.

Membrane proteins are critical mediators for tumor progression and present enormous therapeutic potentials. Although gene profiling can identify their cancer-specific signatures, systematic correlations between protein functions and tumor-related mechanisms are still unclear. We present here the CrMP-Sol database ( https://bio-gateway.aigene.org.cn/g/CrMP ), which aims to breach the gap between the two. Machine learning was used to extract key functional descriptions for protein visualization in the 3D-space, where spatial distributions provide function-based predictive connections between proteins and cancer types. CrMP-Sol also presents QTY-enabled water-soluble designs to facilitate native membrane protein studies despite natural hydrophobicity. Five examples with varying transmembrane helices in different categories were used to demonstrate the feasibility. Native and redesigned proteins exhibited highly similar characteristics, predicted structures and binding pockets, and slightly different docking poses against known ligands, although task-specific designs are still required for proteins more susceptible to internal hydrogen bond formations. The database can accelerate therapeutic developments and biotechnological applications of cancer-related membrane proteins.