Unconventional tonicity-regulated nuclear trafficking of NFAT5 mediated by KPNB1, XPOT and RUVBL2.

NFAT5 is the only known mammalian tonicity-responsive transcription factor with an essential role in cellular adaptation to hypertonic stress. It is also implicated in diverse physiological and pathological processes. NFAT5 activity is tightly regulated by extracellular tonicity, but the underlying mechanisms remain elusive. Here, we demonstrate that NFAT5 enters the nucleus via the nuclear pore complex. We found that NFAT5 utilizes a unique nuclear localization signal (NFAT5-NLS) for nuclear import. siRNA screening revealed that only karyopherin ß1 (KPNB1), but not karyopherin α, is responsible for the nuclear import of NFAT5 via direct interaction with the NFAT5-NLS. Proteomics analysis and siRNA screening further revealed that nuclear export of NFAT5 under hypotonicity is driven by exportin-T (XPOT), where the process requires RuvB-like AAA-type ATPase 2 (RUVBL2) as an indispensable chaperone. Our findings have identified an unconventional tonicity-dependent nucleocytoplasmic trafficking pathway for NFAT5 that represents a critical step in orchestrating rapid cellular adaptation to change in extracellular tonicity. These findings offer an opportunity for the development of novel NFAT5 targeting strategies that are potentially useful for the treatment of diseases associated with NFAT5 dysregulation.

Atovaquone enhances antitumor efficacy of TCR-T therapy by augmentation of ROS-induced ferroptosis in hepatocellular carcinoma.

T-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for tumor treatment, yet hindered by tumor immune evasion resulting in poor therapeutic efficacy. The introduction of ferroptosis-targeted inducers offers a potential solution, as they empower T cells to induce ferroptosis and exert influence over the tumor microenvironment. Atovaquone (ATO) stands as a prospective pharmaceutical candidate with the potential to target ferroptosis, effectively provoking an excessive generation and accumulation of reactive oxygen species (ROS). In this study, we evaluated the effectiveness of a combination therapy comprising ATO and TCR-T cells against hepatocellular carcinoma (HCC), both in vitro and in vivo. The results of lactate dehydrogenase and cytokine assays demonstrated that ATO enhanced cytotoxicity mediated by AFP-specific TCR-T cells and promoted the release of IFN-γ in vitro. Additionally, in an established HCC xenograft mouse model, the combined therapy with low-dose ATO and TCR-T cells exhibited heightened efficacy in suppressing tumor growth, with no apparent adverse effects, comparable to the results achieved through monotherapy. The RNA-seq data unveiled a significant activation of the ferroptosis-related pathway in the combination therapy group in comparison to the TCR-T cells group. Mechanistically, the synergy between ATO and TCR-T cells augmented the release of IFN-γ by TCR-T cells, while concurrently elevating the intracellular and mitochondrial levels of ROS, expanding the labile iron pool, and impairing the integrity of the mitochondrial membrane in HepG2 cells. This multifaceted interaction culminated in the potentiation of ferroptosis within the tumor, primarily induced by an excess of ROS. In summary, the co-administration of ATO and TCR-T cells in HCC exhibited heightened vulnerability to ferroptosis. This heightened susceptibility led to the inhibition of tumor growth and the stimulation of an anti-tumor immune response. These findings suggest that repurposing atovaquone for adoptive cell therapy combination therapy holds the potential to enhance treatment outcomes in HCC.

Function and mechanism of GBP1 in the development and progression of cervical cancer.

Guanylate binding protein 1 (GBP1) is the most concerned member of the GBP family, which has a series of effects such as anti-infection and anti-angiogenesis. Its role in malignant tumors including cervical cancer is still controversial. We aim to explore the effects of GBP1 on cervical cancer through bioinformatics and related experiments. In this study, we first found that GBP1 was generally expressed in cervical cancer in various online databases and was closely related to immune invasion. Secondly, we used multicolor immunofluorescence technology to verify the expression of GBP1 in cervical cancer tissues and its relationship with immune invasion, and explored its relationship with the prognosis of patients with cervical cancer. Knockdown and overexpression assays of GBP1 in vitro were used to prove GBP1 as a potential oncogene of cervical cancer, and its carcinogenicity was verified by in vivo experiment. In order to explore the potential mechanism of GBP1 in promoting cancer, RNA-seq was performed on GBP1 overexpression and knockdown expression cell lines, and GBP1 knockdown and overexpression were found to be associated with many RNA alternative splicing events, suggesting that GBP1 maybe a RNA binding protein (RBP) which affect the biological characteristics of cervical cancer cells through the alternative splicing pathway. However, the later RNA binding protein immunoprecipitation (RIP) assay proved that GBP1 was not a direct alternative splicing factor, while the co-immunoprecipitation (CoIP)-mass spectroscopy (MS) assay combined with protein protein interaction (PPI) analysis proved that 8 alternative splicing factors including Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK) were interacting proteins of GBP1. Combined with the existing reports and the results of RNA-seq alternative splicing analysis, it is speculated that GBP1 may regulate the alternative splicing of CD44 protein by binding to interacting protein-HNRNPK, and thus play a role in promoting cancer in cervical cancer.

Engineering a solar formic acid/pentose (SFAP) pathway in Escherichia coli for lactic acid production.

Microbial CO2 fixation into lactic acid (LA) is an important approach for low-carbon biomanufacturing. Engineering microbes to utilize CO2 and sugar as co-substrates can create efficient pathways through input of moderate reducing power to drive CO2 fixation into product. However, to achieve complete conservation of organic carbon, how to engineer the CO2-fixing modules compatible with native central metabolism and merge the processes for improving bioproduction of LA is a big challenge. In this study, we designed and constructed a solar formic acid/pentose (SFAP) pathway in Escherichia coli, which enabled CO2 fixation merging into sugar catabolism to produce LA. In the SFAP pathway, adequate reducing equivalents from formate oxidation drive glucose metabolism shifting from glycolysis to the pentose phosphate pathway. The Rubisco-based CO2 fixation and sequential reduction of C3 intermediates are conducted to produce LA stoichiometrically. CO2 fixation theoretically can bring a 20% increase of LA production compared with sole glucose feedstock. This SFAP pathway in the integration of photoelectrochemical cell and an engineered Escherichia coli opens an efficient way for fixing CO2 into value-added bioproducts.

Direct Assembly of Bioactive Nanoparticles Constructed from Polyphenol-Nanoengineered Albumin.

Albumin nanoparticles are widely used in biomedicine due to their safety, low immunogenicity, and prolonged circulation. However, incorporating therapeutic molecules into these carriers faces challenges due to limited binding sites, restricting drug conjugation efficiency. We introduce a universal nanocarrier platform (X-UNP) using polyphenol-based engineering to incorporate phenolic moieties into albumin nanoparticles. Integration of catechol or galloyl groups significantly enhances drug binding and broadens the drug conjugation possibilities. Our study presents a library of X-UNP nanoparticles with improved drug-loading efficiency, achieving up to 96% across 10 clinically used drugs, surpassing conventional methods. Notably, ibuprofen-UNP nanoparticles exhibit a 5-fold increase in half-life compared with free ibuprofen, enhancing in vivo analgesic and anti-inflammatory effectiveness. This research establishes a versatile platform for protein-based nanosized materials accommodating various therapeutic agents in biotechnological applications.

Enhancing Protein Solubility via Glycosylation: From Chemical Synthesis to Machine Learning Predictions.

Glycosylation is a valuable tool for modulating protein solubility; however, the lack of reliable research strategies has impeded efficient progress in understanding and applying this modification. This study aimed to bridge this gap by investigating the solubility of a model glycoprotein molecule, the carbohydrate-binding module (CBM), through a two-stage process. In the first stage, an approach involving chemical synthesis, comparative analysis, and molecular dynamics simulations of a library of glycoforms was employed to elucidate the effect of different glycosylation patterns on solubility and the key factors responsible for the effect. In the second stage, a predictive mathematical formula, innovatively harnessing machine learning algorithms, was derived to relate solubility to the identified key factors and accurately predict the solubility of the newly designed glycoforms. Demonstrating feasibility and effectiveness, this two-stage approach offers a valuable strategy for advancing glycosylation research, especially for the discovery of glycoforms with increased solubility.

Winogradskyella pelagia sp. nov., isolated from coastal sediment.

An orange-pigmented, Gram-stain-negative, strictly aerobic, non-flagellated and rod-shaped bacterium, designated strain DF17T, was isolated from coastal sediment collected from Jingzi Wharf, Weihai, PR China. The optimal growth conditions were determined to be at 30 °C, pH 7.5, and in 3 % (w/v) NaCl. According to phylogenetic analysis of the 16S rRNA gene sequence, strain DF17T showed the highest sequence similarity of 96.9 % to Winogradskyella aquimaris KCTC 23502T. The DNA G+C content was 35.8 mol%, and the major fatty acids were iso-C15 : 1 G, iso-C15 : 0, and iso-C17 : 0 3-OH. The major polar lipids were two aminoglycolipids, one phosphatidylethanolamine and four unidentified lipids. The predominant respiratory quinone was menaquinone-6 (MK-6). The average nucleotide identity, digital DNA-DNA hybridization, and amino acid identity values between strain DF17T and other Winogradskyella species were below the species delineation thresholds of 69.35-72.95 %, 16.9-19.6 % and 71.25-78.93 %, respectively. On the basis of its phenotypic, genetic and physiological characteristics, strain DF17T is suggested to represent a novel species of the genus Winogradskyella, for which the name Winogradskyella pelagia sp. nov. is proposed. The type strain is DF17T (MCCC 1H00456T=KCTC 82421T).

Real-world effectiveness and safety of evolocumab in very high-risk atherosclerotic cardiovascular disease patients with acute ischemic stroke.

BACKGROUND: We investigated evolocumab's real-world effectiveness and safety on a background of statin therapy in the acute phase of ischemic stroke (IS) patients with a very high-risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: A real-world, single-center, retrospective study was conducted in the neurology department at Tianjin Huanhu Hospital in China. Patients were divided into two groups: evolocumab treatment (140 mg every two weeks) or the standard of care (SOC) group. The primary efficacy outcome of the study was the achievement of a targeted lipid control rate and the incidence of major adverse cardiovascular events (MACE) by the end of the follow-up. MACE was defined as a composite of various cardiovascular events, cerebrovascular events such as stroke or TIA, and event-related deaths. Propensity score matching (PSM) analysis was utilized to account for confounding factors between groups. Survival analyses were performed using the Kaplan-Meier method and COX regression modeling. RESULTS: 1080 AIS patients with very high-risk ASCVD were recruited. After PSM, there were 528 individuals, with 206 in the evolocumab group and 322 in the SOC group. At 12 months of follow-up, the proportion of LDL-C < 1.4mmol/L and ≥ 50% reduction was 44.91% in the evolocumab group, compared with only 3.12% of SOC-treated patients (p < 0.01). The median follow-up time for clinical events was 15 months. The evolocumab group was associated with a lower risk of cerebrovascular events compared to the SOC group (HR, 0.45; 95% CI, 0.23-0.89; p = 0.02). CONCLUSIONS: This real-world study suggested that evolocumab on a background of statin reduced the LDL-C levels significantly and lowered the incidence of recurrent cerebrovascular events in the very high-risk ASCVD patients with AIS in China.

Early Application of Sacubitril Valsartan Sodium After Acute Myocardial Infarction and its Influence on Ventricular Remodeling and TGF-ß1/Smad3 Signaling Pathway.

Objective: The objective of this study was to investigate the early application of sacubitril valsartan sodium (LCZ696) following acute myocardial infarction (AMI) and its impact on ventricular remodeling and the TGF-ß1/Smad3 signaling pathway in patients. Methods: The clinical data of 73 patients with AMI admitted to the hospital from June 2021 to September 2022 were retrospectively analyzed, and the patients were grouped according to the treatment methods, including 36 cases in the control group (conventional drug treatment) and 37 cases in the observation group (conventional drug + LCZ696 treatment). The clinical efficacy, cardiac function parameters [left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), stroke volume (SV)], cardiac function biochemical indicators [N-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin 3 (Gal-3), amino-terminal peptide of type III procollagen (PIIINP)], ventricular remodeling indicators [left ventricular posterior wall end-diastolic thickness (PWD), posterior wall end-systolic thickness (PWS), ventricular septal end-systolic thickness (IVSS)], ventricular hydrodynamic parameters [left ventricular flow rate in peak ejection (FRPE), flow reversal rate (FRR), flow reversal interval (FRI)], TGF-ß 1/Smad3 signaling pathway-related indicators (TGF-ß1, Smad3), quality of life score (SF-36 Quality of Life Scale) and occurrence of adverse reactions were compared between the two groups. Results: The main findings of the study are as follows: The observation group was significantly better than the control group in many aspects such as overall clinical effectiveness, cardiac function parameters, biochemical indicators, ventricular structure and function, TGF-ß1/Smad3 signaling pathway, and quality of life. Specifically, the observation group showed more significant positive effects in terms of improvement of cardiac function, adjustment of biochemical status, and adjustment of ventricular structure and fluid dynamics parameters. These results provide strong support for the application of new therapeutic approaches in the management of cardiovascular disease. After treatment, the total clinical effective rate in the observation group (89.19%) was significantly higher than that in the control group (69.44%) (P < .05). LVEF and SV in the two groups were significantly increased (P < .05), while LVEDD was significantly decreased (P < .05), and there were statistically significant differences in parameters between the two groups (P < .05). The levels of NT-proBNP, Gal-3 and PIIINP in both groups were significantly reduced (P < .05), and the levels in the observation group were significantly lower than those in the control group (P < .05). The PWD, PWS and IVSS in both groups significantly declined (P < .05), and the indicators in the observation group were significantly lower than those in the control group (P < .05). The FRPE and FRR in the two groups were significantly enhanced (P < .05), while the FRI was significantly reduced (P < .05), and the differences in the above parameters between the two groups were statistically significant (P < .05). The levels of TGF-ß1 and Smad3 in the two groups were significantly declined (P < .05), and the levels in the observation group were significantly lower than those in the control group (P < .05). During the period from before treatment to 6 months of treatment, the quality of life score in the two groups showed a significant downward trend (P < .05), and the score in the observation group after 3 months to 6 months of treatment was significantly lower than that in the control group (P < .05). During treatment, there was no statistical significance in the total incidence rate of adverse reactions between the two groups (P > .05). Conclusion: Early application of LCZ696 after AMI has a significant efficacy, and it can effectively improve the ventricular remodeling, regulate the expression levels of TGF-ß1 and Smad3, inhibit the TGF-ß1/Smad3 signaling pathway, promote the improvements of cardiac function and quality of life, and it has good safety and is worthy of clinical promotion and application. The study's key findings have important clinical implications for understanding and managing acute myocardial infarction (AMI). The observation group showed significant improvements in overall clinical efficacy, cardiac function, biochemical status, ventricular structure and function, etc., providing strong evidence for comprehensive treatment of AMI patients. This treatment method is expected to become an important part of the care and treatment strategy for AMI patients, help reduce cardiovascular risk, improve quality of life, and provide new research directions for future AMI treatment.

The Scar-Hidden Surgery on Gynecomastia: Experiences from a Single-Institutional Large Case Series.

BACKGROUND: To summarize the experiences on the mastoscopic subcutaneous mastectomy for gynecomastia by "nine-step method" based on the "5S" goal and standardize this operation. PATIENTS AND METHODS: Between January 1, 2002, and October 31, 2021, a total of 2035 breasts of 1082 male patients with gynecomastia, of which 129 patients with one side, were underwent mastoscopic subcutaneous mastectomy. The follow-up endpoint was 3 months after surgery. RESULTS: All patients were successfully completed the operation, and none of them was transferred to open operation. The operation time for unilateral breast was 12-28 min, and the average time was 17.7 ± 6.2 min. The amount of bleeding during unilateral operation was very small, about 5-10 ml. The total drainage volume was 5-50 ml after the operation, and the drainage tube was removed in 3-5 days. The epidermal necrosis occurred in 0.3% nipple. 0.2% chest wall had a little ecchymosis in the supero-medial region of the breast. All patients had the normal feeling of nipples and areola, the smoothing and symmetrical chest wall, and the natural contour. There was no recurrence during the follow-up period. CONCLUSIONS: The mastoscopic subcutaneous mastectomy for gynecomastia by "nine-step method" based on the "5S" goal has a short operation time, few surgical complications and good esthetics. It achieves the "5S" goals on the complete removal of glandular tissue (sweeping), small and scar-hidden incision are small (scarless), good symmetry of bilateral chest wall (symmetry), normal chest shape (shape), and smoothing chest wall (smoothing). LEVEL OF EVIDENCE III: The journal asks authors to assign a level of evidence to each article. For a complete description of Evidence-Based Medicine ratings, see the Table of Contents or the online Instructions for Authors at www.springer.com/00266 .

Combined Mindfulness-Based Stress Reduction and Exercise Intervention for Improving Psychological Well-Being in Patients With Non-Small Cell Lung Cancer.

OBJECTIVE: This study aims to assess the clinical effectiveness of combining mindfulness-based stress reduction (MBSR) with exercise intervention in improving anxiety, depression, sleep quality and mood regulation in patients with non-small cell lung cancer (NSCLC). METHODS: A total of 60 patients with NSCLC who had not received surgical treatment were selected using convenience sampling and divided into an intervention group and control group, with 30 patients in each group. The control group received conventional psychological nursing care, whereas the intervention group received a combination of MBwSR and exercise therapy. Before the intervention, a questionnaire was completed to collect the basic data of the two groups. Further questionnaires were administered at 6 and 8 weeks after treatment to assess anxiety, depression, sleep quality and other items included in the five-item Brief Symptom Rating Scale (BSRS-5). RESULTS: No significant differences between the intervention and control groups were identified in terms of personal and clinical characteristics (p > 0.05). No significant differences were determined in the BSRS-5, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) or Pittsburgh Sleep Quality Index (PSQI) scores between the intervention and control groups before the intervention. However, 6 and 8 weeks after the intervention, scores were significantly lower in both groups (p < 0.001). Significant differences in the BSRS-5, SAS, SDS and PSQI scores were identified between the two groups at different time points (p < 0.001). CONCLUSION: The combination of MBSR and exercise intervention demonstrated improvements in anxiety, depression, sleep quality and BSRS-5 scores in patients with NSCLC.

Metal-Phenolic Nanocloaks on Cancer Cells Potentiate STING Pathway Activation for Synergistic Cancer Immunotherapy.

Due to the presence of natural neoantigens, autologous tumor cells hold great promise as personalized therapeutic vaccines. Yet autologous tumor cell vaccines require multi-step production that frequently leads to the loss of immunoreactive antigens, causing insufficient immune activation and significantly hampering their clinical applications. Herein, we introduce a novel whole-cell cancer vaccine by cloaking cancer cells with lipopolysaccharide-decorated manganese(II)-phenolic networks (MnTA nanocloaks) to evoke tumor-specific immune response for highly efficacious synergistic cancer immunotherapy. The natural polyphenols coordinate with Mn2+ and immediately adhere to the surface of individual cancer cells, thereby forming a nanocloak and encapsulating tumor neoantigens. Subsequent decoration with lipopolysaccharide induces internalization by dendritic cells, where Mn2+ ions are released in the cytosol, further facilitating the activation of the stimulator of the interferon genes (STING) pathway. Highly effective tumor suppression was observed by combining the nanocloaked cancer cell treatment with anti-programmed cell death ligand 1 (anti-PD-L1) antibodies-mediated immune checkpoint blockade therapy. Our work demonstrates a universal yet simple strategy to engineer a cell-based nanobiohybrid system for enhanced cancer immunotherapy.

Mechanism of Taxanes in the Treatment of Lung Cancer Based on Network Pharmacology and Molecular Docking.

Taxanes are natural compounds for the treatment of lung cancer, but the molecular mechanism behind the effects is unclear. In the present study, through network pharmacology and molecular docking, the mechanism of the target and pathway of taxanes in the treatment of lung cancer was studied. The taxanes targets were determined by PubChem database, and an effective compounds-targets network was constructed. The GeneCards database was used to determine the disease targets of lung cancer, and the intersection of compound targets and disease targets was obtained. The Protein-Protein Interaction (PPI) network of the intersection targets was analyzed, and the PPI network was constructed by Cytoscape 3.6.0 software. The hub targets were screened according to the degree value, and the binding activity between taxanes and hub targets was verified by molecular docking. The results showed that eight taxane-active compounds and 444 corresponding targets were screened out, and 131 intersection targets were obtained after mapping with lung cancer disease targets. The hub targets obtained by PPI analysis were TP53, EGFR, and AKT1. Gene Ontology (GO) biological function enrichment analysis obtained 1795 biological process (BP) terms, 101 cellular component (CC) terms, and 164 molecular function (MF) terms. There were 179 signaling pathways obtained by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Twenty signaling pathways were screened out, mainly pathways in cancer, proteoglycans in cancer pathway, microRNAs in cancer pathway, and so on. Molecular docking shows that the binding energies of eight taxanes with TP53, EGFR, and AKT1 targets were less than -8.8 kcal/mol, taxanes acts on TP53, EGFR, and AKT1 targets through pathways in cancer, proteoglycans in cancer pathway and microRNAs in cancer pathway, and plays a role in treating lung cancer in biological functions such as protein binding, enzyme binding, and identical protein binding.

Systematic analysis of the Rboh gene family in seven gramineous plants and its roles in response to arbuscular mycorrhizal fungi in maize.

BACKGROUND: Plant respiratory burst oxidase homolog (Rboh) gene family produces reactive oxygen species (ROS), and it plays key roles in plant-microbe interaction. Most Rboh gene family-related studies mainly focused on dicotyledonous plants; however, little is known about the roles of Rboh genes in gramineae. RESULTS: A total of 106 Rboh genes were identified in seven gramineae species, including Zea mays, Sorghum bicolor, Brachypodium distachyon, Oryza sativa, Setaria italica, Hordeum vulgare, and Triticum aestivum. The Rboh protein sequences showed high similarities, suggesting that they may have conserved functions across different species. Duplication mode analysis detected whole-genome/segmental duplication (WGD)/(SD) and dispersed in the seven species. Interestingly, two local duplication (LD, including tandem and proximal duplication) modes were found in Z. mays, S. italica and H. vulgare, while four LD were detected in T. aestivum, indicating that these genes may have similar functions. Collinearity analysis indicated that Rboh genes are at a stable evolution state in all the seven species. Besides, Rboh genes from Z. mays were closely related to those from S. bicolor, consistent with the current understanding of plant evolutionary history. Phylogenetic analysis showed that the genes in the subgroups I and II may participate in plant-AM fungus symbiosis. Cis-element analysis showed that different numbers of elements are related to fungal induction in the promoter region. Expression profiles of Rboh genes in Z. mays suggested that Rboh genes had distinct spatial expression patterns. By inoculation with AM fungi, our transcriptome analysis showed that the expression of Rboh genes varies upon AM fungal inoculation. In particularly, ZmRbohF was significantly upregulated after inoculation with AM fungi. pZmRbohF::GUS expression analyses indicated that ZmRbohF was induced by arbuscular mycorrhizal fungi in maize. By comparing WT and ZmRbohF mutant, we found ZmRbohF had limited impact on the establishment of maize-AM fungi symbiosis, but play critical roles in regulating the proper development of arbuscules. CONCLUSIONS: This study provides a comprehensive analysis of the evolution relationship of Rboh genes in seven gramineae species. Results showed that several Rboh genes regulate maize-AM fungal symbiosis process. This study provides valuable information for further studies of Rboh genes in gramineae.

Simultaneous superresolution reconstruction and distortion correction for single-shot EPI DWI using deep learning.

PURPOSE: Single-shot (SS) EPI is widely used for clinical DWI. This study aims to develop an end-to-end deep learning-based method with a novel loss function in an improved network structure to simultaneously increase the resolution and correct distortions for SS-EPI DWI. THEORY AND METHODS: Point-spread-function (PSF)-encoded EPI can provide high-resolution, distortion-free DWI images. A distorted image from SS-EPI can be described as the convolution between a PSF function with a distortion-free image. The deconvolution process to recover the distortion-free image can be achieved with a convolution neural network, which also learns the mapping function between low-resolution SS-EPI and high-resolution reference PSF-EPI to achieve superresolution. To suppress the oversmoothing effect, we proposed a modified generative adversarial network structure, in which a dense net with gradient map guidance and a multilevel fusion block was used as the generator. A fractional anisotropy loss was proposed to utilize the diffusion anisotropy information among diffusion directions. In vivo brain DWI data were used to test the proposed method. RESULTS: The results show that distortion-corrected high-resolution DWI images with restored structural details can be obtained from low-resolution SS-EPI images by taking advantage of the high-resolution anatomical images. Additionally, the proposed network can improve the quantitative accuracy of diffusion metrics compared with previously reported networks. CONCLUSION: Using high-resolution, distortion-free EPI-DWI images as references, a deep learning-based method to simultaneously increase the perceived resolution and correct distortions for low-resolution SS-EPI was proposed. The results show that DWI image quality and diffusion metrics can be improved.

A case report of a brain abscess due to prevotella oris and a review of the literature.

BACKGROUND: Brain abscesses caused by Prevotella oris are rarely reported. Here, we described a case of a brain infection caused by Prevotella oris that was detected by metagenomic next-generation sequencing (mNGS). CASE PRESENTATION: A 63-year-old man with no medical history reported headache in the right frontotemporal region, fever, and intermittent diplopia. Magnetic resonance imaging (MRI) revealed abnormal signals and enhancement changes in the superior sellar region. mNGS testing showed that cerebrospinal fluid collected from the spine was positive for Prevotella oris. After receiving a combined treatment of antibiotic therapy, the patient recovered well. CONCLUSION: We reviewed the relevant literature and summarized the characteristics and prognosis of this type of bacterial infection to provide ideas for clinicians to diagnose and treat this disease.

Design, synthesis, antitumor activity, and molecular dynamics simulations of novel sphingosine kinase 2 inhibitors.

Targeting sphingosine kinase 2 (SphK2) has become a novel strategy for the treatment of cancer. However, potent and selective SphK2 inhibitors are rare. In our work, a series of novel SphK2 inhibitors were innovatively designed, synthesized and screened. Compound 12e showed the best inhibitory activity. Molecular dynamics simulations were carried out to analyze the detailed interactions between the SphK2 and its inhibitors. Moreover, 12e exhibited anti-proliferative activity in various cancer cells, and inhibited the migration of human breast cancer cells MCF-7.

Molecular dynamics simulation and non-isothermal crystallization kinetics of polyamide 4 and different bio-based polyamide blends.

The effects of the structural units and blending ratio on the crystallization behavior of blends of polyamide 4 (PA4) with polyamide 56 (PA56) and polyamide 11 (PA11) were studied using molecular dynamics simulations and non-isothermal crystallization kinetics. The simulation results show that the crystallinity of PA4/PA56 blends (B4/56) with a PA56 content of 30-50% was 3.5-10.8% lower than that of B4/56 with a PA56 content of 20%, and the crystallinity of PA4/PA11 blends (B4/11) decreased by 9.5% as PA11 content increased from 20% to 50%. The experimental results show that both B4/56 and B4/11 form PA4- and PA56-rich (PA11-rich) phases through crystallization-induced phase separation. The interplanar spacing of the PA4-rich phase of B4/56 changed relative to that of PA4, indicating that some PA56 entered the PA4-rich phase unit cell. As the PA56 content increased from 20% to 50%, the crystallinity of B4/56 decreased by 11.2%, and the crystallization-induced phase separation grew distinct. The B4/56 with a higher PA4 content crystallized more easily. As the PA11 content increased from 20% to 50%, the crystallinity of B4/11 decreased by 12.5%, and PA11 barely participated in the crystallization of the PA4-rich phase. The blending ratio had no significant effect on the crystallization rate and crystal-growth degree of B4/11, and the non-isothermal crystallization activation energy of B4/11 was significantly higher than that of B4/56, indicating that the crystallization ability of the B4/11 blend system is worse. This study provides a theoretical basis for the design and performance regulation of PA4-based polyamide blends.

Nanomedicine for renal cell carcinoma: imaging, treatment and beyond.

The kidney is a vital organ responsible for maintaining homeostasis in the human body. However, renal cell carcinoma (RCC) is a common malignancy of the urinary system and represents a serious threat to human health. Although the overall survival of RCC has improved substantially with the development of cancer diagnosis and management, there are various reasons for treatment failure. Firstly, without any readily available biomarkers, timely diagnosis has been greatly hampered. Secondly, the imaging appearance also varies greatly, and its early detection often remains difficult. Thirdly, chemotherapy has been validated as unavailable for treating renal cancer in the clinic due to its intrinsic drug resistance. Concomitant with the progress of nanotechnological methods in pharmaceuticals, the management of kidney cancer has undergone a transformation in the recent decade. Nanotechnology has shown many advantages over widely used traditional methods, leading to broad biomedical applications ranging from drug delivery, prevention, diagnosis to treatment. This review focuses on nanotechnologies in RCC management and further discusses their biomedical translation with the aim of identifying the most promising nanomedicines for clinical needs. As our understanding of nanotechnologies continues to grow, more opportunities to improve the management of renal cancer are expected to emerge.

A dual-modality immunosensor for simple and reliable detection of nitrated alpha-synuclein in serum based on silver-coated MOF.

Nitrated α-syn (nitro-α-syn) is a biomarker for Parkinson's desease (PD), and its sensitive detection in serum is of great importance for early PD diagnosis. Silver-coated copper MOF (Cu-MOF@Ag) with outstanding oxidase activity and electrochemical response property was designed and synthesized. Cu-MOF@Ag exhibited excellent oxidase activity with a low Km value (0.568 mM), avoiding the addition of strong oxidant to catalyze chromogenic substrate, which enhanced the colorimetric stability. Silver nanoparticles as an electrochemical signal reporter can be easily decorated on the surface of Cu-MOF with bifunctional groups (-SH and -NH2) material, which can increase the electrochemical signal output. The α-syn antibody modified Cu-MOF@Ag and nitro-α-syn modified magnetic nanoparticle were used as immunoprobes to specifically capture nitro-α-syn. A dual-modal immunosensor was fabricated for the simple and reliable detection of nitro-α-syn based on Cu-MOF@Ag. Combing colorimetric and electrochemical detection, nitro-α-syn can be determined quantitatively within a wide linear range (10-350 ng/mL) with low detection limit (0.5 ng/mL). The ability of the sensor with magnetic separation and dual signal analysis allowed to successfully detect nitro-α-syn and distinguish PD patients from healthy people (P < 0.005). Thanks to its excellent selectivity, stability, and the precision of 2.69%, the dual-modal sensor has potential clinical application for nitro-α-syn detection and paves a new way for PD diagnosis at its early stage.