Emerging Role of ABC Transporters in Glia Cells in Health and Diseases of the Central Nervous System.

ATP-binding cassette (ABC) transporters play a crucial role for the efflux of a wide range of substrates across different cellular membranes. In the central nervous system (CNS), ABC transporters have recently gathered significant attention due to their pivotal involvement in brain physiology and neurodegenerative disorders, such as Alzheimer's disease (AD). Glial cells are fundamental for normal CNS function and engage with several ABC transporters in different ways. Here, we specifically highlight ABC transporters involved in the maintenance of brain homeostasis and their implications in its metabolic regulation. We also show new aspects related to ABC transporter function found in less recognized diseases, such as Huntington's disease (HD) and experimental autoimmune encephalomyelitis (EAE), as a model for multiple sclerosis (MS). Understanding both their impact on the physiological regulation of the CNS and their roles in brain diseases holds promise for uncovering new therapeutic options. Further investigations and preclinical studies are warranted to elucidate the complex interplay between glial ABC transporters and physiological brain functions, potentially leading to effective therapeutic interventions also for rare CNS disorders.

Parents' experience of children's transitions from intensive care unit after liver transplantation: A qualitative study.

OBJECTIVE: The aim of this study was to understand parents' perspectives on caring for children who underwent liver transplantation in the intensive care unit transition period and to provide a reference for the development of targeted intervention strategies. METHODS: Thirteen parents of children who underwent liver transplantation at a tertiary hospital in Hangzhou, Zhejiang Province were chosen for in-depth semi-structured interviews via purposive sampling. The interview data were analyzed and summarized via content analysis. FINDINGS: Three themes were extracted, including a period of separation and suffering (being apart from child is tough, chilling atmosphere, and limited family access); being an overwhelming caregiver (hope coupled with worry, conflict of roles, and existential care dilemmas); and facing a new normal: searching for information and support (information on medical conditions, post-discharge care assistance, educational support, and peer support). CONCLUSION: For parents whose child underwent liver transplantation, the transition period from the intensive care unit to the general ward is challenging. Parents are burdened with several caregiving responsibilities and require a variety of information and support. It is advised that nurses should offer sufficient information and suitable educational approaches to enhance these parents' capacity to care for their children and assist children and their parents in making a smooth transition. IMPLICATIONS FOR CLINICAL PRACTICE: This study highlights parents' perspectives on caring for children with liver transplants transferred from the intensive care unit to a general ward. Transitional care is strenuous, evoking different feelings before and after transfer. The health care professionals should focus on the needs and challenges faced by parents who are caring for children with liver transplants during the intensive care unit transition period. To achieve this, it is critical to establish a supportive environment and provide suitable information and education for parents to enhance their caregiving abilities.

Identification and Characterization of CC-AMP1-like and CC-AMP2-like Peptides in Capsicum spp.

Antimicrobial peptides (AMPs) are compounds with a variety of bioactive properties. Especially promising are their antibacterial activities, often toward drug-resistant pathogens. Across different AMP sources, AMPs expressed within plants are relatively underexplored with a limited number of plant AMP families identified. Recently, we identified the novel AMPs CC-AMP1 and CC-AMP2 in ghost pepper plants (Capsicum chinense x frutescens), exerting promising antibacterial activity and not classifying into any known plant AMP family. Herein, AMPs related to CC-AMP1 and CC-AMP2 were identified within both Capsicum annuum and Capsicum baccatum. In silico predictions throughout plants were utilized to illustrate that CC-AMP1-like and CC-AMP2-like peptides belong to two broader AMP families, with three-dimensional structural predictions indicating that CC-AMP1-like peptides comprise a novel subfamily of α-hairpinins. The antibacterial activities of several closely related CC-AMP1-like peptides were compared with a truncated version of CC-AMP1 possessing significantly more activity than the full peptide. This truncated peptide was further characterized to possess broad-spectrum antibacterial activity against clinically relevant ESKAPE pathogens. These findings illustrate the value in continued study of plant AMPs toward characterization of novel AMP families, with CC-AMP1-like peptides possessing promising bioactivity.

Apolar Extracts of St. John's Wort Alleviate the Effects of ß-Amyloid Toxicity in Early Alzheimer's Disease.

Hypericum perforatum (St. John's wort) has been described to be beneficial for the treatment of Alzheimer's disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp. extracts with a low hypericin and hyperforin content to reduce side effects such as phototoxicity. In order to systematically elucidate the therapeutic effects of H. perforatum extracts with different polarities, APP-transgenic mice were treated with a total ethanol extract (TE), a polar extract obtained from TE, and an apolar supercritical CO2 (scCO2) extract. The scCO2 extract was formulated with silicon dioxide (SiO2) for better oral application. APP-transgenic mice were treated with several extracts (total, polar, apolar) at different concentrations. We established an early treatment paradigm from the age of 40 days until the age of 80 days, starting before the onset of cerebral ß-amyloid (Aß) deposition at 45 days of age. Their effects on intracerebral soluble and insoluble Aß were analyzed using biochemical analyses. Our study confirms that the scCO2H. perforatum formulation shows better biological activity against Aß-related pathological effects than the TE or polar extracts. Clinically, the treatment resulted in a dose-dependent improvement in food intake with augmentation of the body weight, and, biochemically, it resulted in a significant reduction in both soluble and insoluble Aß (-27% and -25%, respectively). We therefore recommend apolar H. perforatum extracts for the early oral treatment of patients with mild cognitive impairment or early AD.

Lung-PNet: An Automated Deep Learning Model for the Diagnosis of Invasive Adenocarcinoma in Pure Ground-Glass Nodules on Chest CT.

BACKGROUND. Pure ground-glass nodules (pGGNs) on chest CT representing invasive adenocarcinoma (IAC) warrant lobectomy with lymph node resection. For pGGNs representing other entities, close follow-up or sublobar resection without node dissection may be appropriate. OBJECTIVE. The purpose of this study was to develop and validate an automated deep learning model for differentiation of pGGNs on chest CT representing IAC from those representing atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA). METHODS. This retrospective study included 402 patients (283 women, 119 men; mean age, 53.2 years) with a total of 448 pGGNs on noncontrast chest CT that were resected from January 2019 to June 2022 and were histologically diagnosed as AAH (n = 29), AIS (n = 83), MIA (n = 235), or IAC (n = 101). Lung-PNet, a 3D deep learning model, was developed for automatic segmentation and classification (probability of IAC vs other entities) of pGGNs on CT. Nodules resected from January 2019 to December 2021 were randomly allocated to training (n = 327) and internal test (n = 82) sets. Nodules resected from January 2022 to June 2022 formed a holdout test set (n = 39). Segmentation performance was assessed with Dice coefficients with radiologists' manual segmentations as reference. Classification performance was assessed by ROC AUC and precision-recall AUC (PR AUC) and compared with that of four readers (three radiologists, one surgeon). The code used is publicly available (https://github.com/XiaodongZhang-PKUFH/Lung-PNet.git). RESULTS. In the holdout test set, Dice coefficients for segmentation of IACs and of other lesions were 0.860 and 0.838, and ROC AUC and PR AUC for classification as IAC were 0.911 and 0.842. At threshold probability of 50.0% or greater for prediction of IAC, Lung-PNet had sensitivity, specificity, accuracy, and F1 score of 50.0%, 92.0%, 76.9%, and 60.9% in the holdout test set. In the holdout test set, accuracy and F1 score (p values vs Lung-PNet) for individual readers were as follows: reader 1, 51.3% (p = .02) and 48.6% (p = .008); reader 2, 79.5% (p = .75) and 75.0% (p = .10); reader 3, 66.7% (p = .35) and 68.3% (p < .001); reader 4, 71.8% (p = .48) and 42.1% (p = .18). CONCLUSION. Lung-PNet had robust performance for segmenting and classifying (IAC vs other entities) pGGNs on chest CT. CLINICAL IMPACT. This automated deep learning tool may help guide selection of surgical strategies for pGGN management.

Comparison of Targeted Biopsy and Combined Biopsy to Avoid Unnecessary Systematic Biopsy in Patients with PI-RADS 5 Lesions.

PURPOSE: To evaluate the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CSPCa) detection via target biopsy (TB), systematic biopsy (SB), and combined biopsy (CB) in patients with PI-RADS 5 lesions. METHODS: Patients with at least one PI-RADS 5 lesion were retrospectively enrolled in a prospectively collected database. The patients underwent multiparametric magnetic resonance imaging (mpMRI) followed by transrectal TB of PI-RADS 5 lesions and SB. The PCa and CSPCa detection rates and cores of TB and SB were compared with those of CB. RESULTS: In 585 patients, prostate biopsy revealed PCa in 560 cases (95.73%) and CSPCa in 549 cases (93.85%). PCa was detected in T2 patients (93.13%, 217/233) and in T3/4 patients (97.44%, 343/352). CSPCa was detected in T2 patients (89.27%, 208/233) and in T3/4 patients (96.87%, 341/352). The positive rates of TB for T2/3/4, T3/4, and T2 were 94.02%, 96.21%, and 90.56%, respectively. SB added 1.71% (10/585) PCa and 1.37% (8/585) CSPCa detection to TB. There was no difference between TB and SB in detecting different stages of cancer (p > 0.05). In the biopsy core analysis, TB had fewer biopsy cores and a higher detection rate than SB (all p < 0.05). CONCLUSIONS: In patients with PI-RADS score 5 lesions, TB can achieve the same detection rate as, with fewer biopsy cores than, CB. SB adds minimal clinical value and can be omitted for these patients.

Organocatalytic Asymmetric [4 + 2] Cyclization of Azadienes with Azlactones: Access to Chiral 3-Amino-δ-Lactams Derivatives.

Herein, a series of chiral δ-lactam frameworks have been synthesized and catalyzed by chiral phosphoric acid (CPA) utilizing two kinds of open-chain aza-dienes and azlactones derived from amino acids. This powerful [4 + 2] annulation produces a broad substrate scope with functional group tolerance in yield up to 97% with up to 98:2 er. Moreover, a facile scale-up and straightforward conversion to diversely substituted products verify the synthetic utility of this method featuring good compatibility and high efficiency.

Zinc(II)-Based Ring-and-Rod Coordination Layer as an Excitation-Wavelength-dependent Dual-Emissive Chemosensor for Discriminating Fe3+, Cr3+, and Al3+ in Water.

The reactions of Zn(NO3)2, 3,6-bis(pyridin-3-yl)-9H-carbazole (bpycz), and 2,5-dihydroxyterephthalic acid (H4dhbdc) or 2-bromoterephthalic acid (Br-1,4-H2bdc) under hydro(solvo)thermal conditions yielded corresponding coordination polymers (CPs) {[Zn(H2dhbdc)(bpycz)]•0.5H2O}n (1) and [Zn(Br-1,4-bdc)(bpycz)]•2DMAc•H2O (2), respectively, with high thermal stability approaching 350 °C. CP 1 adopts a ring-and-rod layer structure, which is topologically described as a 4-connected net with the point symbol of 2•65. Two layers are interpenetrated in parallel interlocking mode to form a double 2D → 2D polyrotaxane entanglement with extra-framework void space of 19.6%. CP 2 has a non-interpenetrating ring-and-rod layer structure of 4-connected 2•65 net topology, with extra-framework void space of 16.6%. Thermally activated 1 and 2 revealed CO2 uptakes of 101.1 and 98.6 cm3 g-1, respectively, at P/P0 = 1 and 195 K. X-ray powder diffraction (XRPD) patterns confirmed that 1 and 2 both possessed high chemical stability in H2O, CH3OH, acetone, and DMF, and framework stability during gas adsorption-desorption. The H2O suspension of 1 displayed excitation-dependent dual-emissive properties, appearing at 432 nm upon excitation at 300 nm and at 528 nm upon excitation at 365 nm. Of note, 1 was capable of detection of Fe3+, Cr3+, and Al3+ ions in H2O, showing good anti-interference ability, excellent selectivity, and high sensitivity. More interesting, the dual-emissive properties make 1 to be an excellent luminescence chemosensor to screen Fe3+, Cr3+, and Al3+ from a pool of metal ions in H2O upon excitation at 300 nm via luminescence quenching effect and then discriminate Fe3+, Cr3+, and Al3+ upon excitation at 365 nm via luminescence quenching, unaltered, and enhancement responses, respectively. On the other hand, the H2O suspension of 2 demonstrated an excitation-independent emission appearing at around 430 nm, which could be utilized to sensitively detect Fe3+ and Cr3+ ions with good anti-interference ability and excellent selectivity via luminescence quenching effect. Further, 1 and 2 were recyclability and possessed cycling stability. The plausible sensing mechanisms for 1 and 2 toward Fe3+, Cr3+, and Al3+ were also explored in detail.

ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer's Disease.

Alzheimer's disease (AD), the leading cause of dementia, is a growing health issue with very limited treatment options. To meet the need for novel therapeutics, existing drugs with additional preferred pharmacological profiles could be recruited. This strategy is known as 'drug repurposing'. Here, we describe dimethyl fumarate (DMF), a drug approved to treat multiple sclerosis (MS), to be tested as a candidate for other brain diseases. We used an APP-transgenic model (APPtg) of senile ß-amyloidosis mice to further investigate the potential of DMF as a novel AD therapeutic. We treated male and female APPtg mice through drinking water at late stages of ß-amyloid (Aß) deposition. We found that DMF treatment did not result in modulating effects on Aß deposition at this stage. Interestingly, we found that glutathione-modified DMF interacts with the ATP-binding cassette transporter ABCC1, an important gatekeeper at the blood-brain and blood-plexus barriers and a key player for Aß export from the brain. Our findings suggest that ABCC1 prevents the effects of DMF, which makes DMF unsuitable as a novel therapeutic drug against AD. The discovered effects of ABCC1 also have implications for DMF treatment of multiple sclerosis.

The experiences of adolescent solid organ transplantation recipients, parents, and healthcare professionals in healthcare transition: A qualitative systematic review.

PROBLEM: The transition from paediatric-centred to adult healthcare services in adolescent solid organ transplantation recipients is a period of increased risk and vulnerability, the issues related to healthcare transition have become key concerns to the healthcare community. ELIGIBILITY CRITERIA: Qualitative studies of any design and qualitative components of mixed method studies that explored the experiences of healthcare transition among adolescent solid organ transplant recipients, parents, and healthcare professionals were included. SAMPLE: Nine articles were finalised and included in the review. METHODS: A systematic review of qualitative studies was conducted. Databases searched were Scopus, PsycINFO, EMBASE, Web of Science, PubMed, CINAHL and ProQuest Dissertations and Theses. Studies published between the inception of respective database and December 2022 inclusive were considered. A three-step inductive thematic synthesis method outlined by Thomas and Harden was used to form descriptive themes and the 10-item Joanna Briggs Institute Critical Appraisal Checklist was utilised to appraise the quality of included articles. RESULTS: Two hundred and twenty studies were screened, and 9 studies published between 2013 and 2022 were included. Five analytical themes were generated: 'the struggle of being an adolescent with a transplant'; 'perceptions of transition'; 'the role of parents'; 'lack of transition readiness' and 'the need for better support'. CONCLUSIONS: Adolescent solid organ transplant recipients, parents, and healthcare professionals faced multiple challenges in the healthcare transition. IMPLICATIONS: Future interventions and health policies should provide targeted intervention strategies that address the barriers present in the healthcare transition to facilitate the optimization of the youth healthcare transition.

A neutral rhenium-biimidazole complex for the selective recognition of fluoride ions.

The neutral rhenium(I)-biimidazole complex [Re(CO)3(biimH)(1,4-NVP)] (1) was designed and synthesized by a one-pot reaction of Re2(CO)10, 2,2'-biimidazole (biimH2) and 4-(1-naphthylvinyl)pyridine (1,4-NVP). The structure of 1 was characterized by various spectroscopic techniques including IR, 1H NMR, FAB-MS, and elemental analysis and further confirmed by a single-crystal X-ray diffraction analysis. The mononuclear complex 1, a relatively simple structure with an octahedral geometry, is comprised of facial-arranged carbonyl groups, one chelated biimH monoanion, and one 1,4-NVP. Complex 1 shows the lowest energy absorption band at around 357 nm and an emission band at 408 nm in THF. The luminescent characteristics of 1 combined with the hydrogen bonding ability of the partially coordinated monoionic biimidazole ligand permits the complex to selectively recognize fluoride ions (F-) in the presence of other halides through a dramatic luminescence enhancement. The recognition mechanism of 1 can be convincingly explained in terms of H-bond formation and proton abstraction upon the addition of F- ions by 1H and 19F NMR titration experiments. The electronic properties of 1 were further supported by time dependent density functional theory (TDDFT) computational studies.

Organocatalytic atroposelective synthesis of naphthoquinone thioglycosides from aryl-naphthoquinones and thiosugars.

In this study, we report an organocatalytic formal coupling strategy for aryl-naphthoquinones with thiosugars that provides straightforward access to the axially chiral naphthoquinone thioglycoside with excellent stereoselectivity. Mechanistic studies revealed the key role of H-bonding in stereochemical recognition. The reaction pathway involves the atroposelective addition, followed by stereoretentive oxidation of the hydroquinone intermediate.

Genome-wide identification of RNA modification-related single nucleotide polymorphisms associated with rheumatoid arthritis.

BACKGROUND: RNA modification plays important roles in many biological processes, such as gene expression control. The aim of this study was to identify single nucleotide polymorphisms related to RNA modification (RNAm-SNPs) for rheumatoid arthritis (RA) as putative functional variants. METHODS: We examined the association of RNAm-SNPs with RA in summary data from a genome-wide association study of 19,234 RA cases and 61,565 controls. We performed eQTL and pQTL analyses for the RNAm-SNPs to find associated gene expression and protein levels. Furthermore, we examined the associations of gene expression and circulating protein levels with RA using two-sample Mendelian randomization analysis methods. RESULTS: A total of 160 RNAm-SNPs related to m6A, m1A, A-to-I, m7G, m5C, m5U and m6Am modifications were identified to be significantly associated with RA. These RNAm-SNPs were located in 62 protein-coding genes, which were significantly enriched in immune-related pathways. RNAm-SNPs in important RA susceptibility genes, such as PADI2, SPRED2, PLCL2, HLA-A, HLA-B, HLA-DRB1, HLA-DPB1, TRAF1 and TXNDC11, were identified. Most of these RNAm-SNPs showed eQTL effects, and the expression levels of 26 of the modifiable genes (e.g., PADI2, TRAF1, HLA-A, HLA-DRB1, HLA-DPB1 and HLA-B) in blood cells were associated with RA. Circulating protein levels, such as CFB, GZMA, HLA-DQA2, IL21, LRPAP1 and TFF3, were affected by RNAm-SNPs and were associated with RA. CONCLUSION: The present study identified RNAm-SNPs in the reported RA susceptibility genes and suggested that RNAm-SNPs may affect RA risk by affecting the expression levels of corresponding genes and proteins.

Excitation-Wavelength-Dependent Luminescence of Chemically and Physically Mixed Europium and Terbium Phosphonates: Color-Tunable Luminescence, Near-White-Light Emission, and Selective Fe3+ Detection.

Molecular lanthanide phosphonates [Ln2 (H3 tpmm)2 (H2 O)6 ] ⋅ xH2 O (Ln=Eu, EuP; Ln=Tb, TbP) were synthesized. Single-crystal X-ray diffraction confirmed that EuP has a sandwich-like dinuclear structure, in which the Eu(III) center adopts a {EuO8 } distorted dodecahedral geometry. XRPD patterns prove that TbP and EuP are isomorphous and isostructural. EuP and TbP are highly thermally stable approaching 450 °C and exhibit red- and green-light emissions from the characteristic 4 f-4 f transition of the Eu3+ and Tb3+ , respectively. Interestingly, luminescence modulation is achieved for the chemically mixed Eu/Tb phosphonate analogues, c-Eux Tb2 -x P (x=1.5, 1, 0.5), and physically mixed Eu/Tb phosphonate materials, p-yEuP : zTbP (y : z=3 : 1, 1 : 1, 1 : 3), with varying the excitation wavelength. Of particular note, near-white-light emission is also achieved for c-EuTbP, p-EuP : TbP, and p-EuP : 3TbP when excited at 365 nm. Therefore, these dinuclear molecular lanthanide phosphonates emitting excitation wavelength and Eu3+ : Tb3+ ratio dependent luminescence might be potential candidates for color-tunable luminescence materials and white-light-emitting materials. On the other hand, the bright green-light emission makes TbP to be an excellent reusable luminescence sensor for selective detection of Fe3+ with Stern-Volmer quenching constant (KSV ) of 9.66×103  M-1 and detection limit (DL) of 0.42 µM through absorption competition caused luminescence quenching effect.

Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia. Fingolimod has previously shown beneficial effects in different animal models of AD. However, it has shown contradictory effects when it has been applied at early disease stages. Our objective was to evaluate fingolimod in two different treatment paradigms. To address this aim, we treated male and female APP-transgenic mice for 50 days, starting either before plaque deposition at 50 days of age (early) or at 125 days of age (late). To evaluate the effects, we investigated the neuroinflammatory and glial markers, the Aß load, and the concentration of the brain-derived neurotrophic factor (BDNF). We found a reduced Aß load only in male animals in the late treatment paradigm. These animals also showed reduced microglia activation and reduced IL-1ß. No other treatment group showed any difference in comparison to the controls. On the other hand, we detected a linear correlation between BDNF and the brain Aß concentrations. The fingolimod treatment has shown beneficial effects in AD models, but the outcome depends on the neuroinflammatory state at the start of the treatment. Thus, according to our data, a fingolimod treatment would be effective after the onset of the first AD symptoms, mainly affecting the neuroinflammatory reaction to the ongoing Aß deposition.

Aggregation-induced emission enhancement (AIEE) of tetrarhenium(I) metallacycles and their application as luminescent sensors for nitroaromatics and antibiotics.

The self-assembly of tetrarhenium metallacycles [{Re(CO)3}2(µ-dhaq)(µ-N-N)]2 (3a, N-N = 1,3-bis(1-butylbenzimidazol-2-yl)benzene; 3b, N-N = 1,3-bis(1-octylbenzimidazol-2-yl)benzene), (H2-dhaq = 1,4-dihydroxy-9,10-anthraquinone) and [{Re(CO)3}2(µ-thaq)(µ-N-N)]2 (4, N-N = 1,3-bis(1-butylbenzimidazol-2-yl)benzene), (H2-thaq = 1,2,4-trihydroxy-9,10-anthraquinone) under solvothermal conditions is described. The metallacycles 3a,b and 4 underwent aggregation-induced emission enhancement (AIEE) in THF upon the incremental addition of water. TEM images revealed that metallacycle 3a in a 60% aqueous THF solution formed rectangular aggregates with a wide size distribution, while a 90% aqueous THF solution resulted in the formation of a mixture of nanorods and amorphous aggregates due to rapid and abrupt aggregation. UV-vis and emission spectral profiles supported the formation of nanoaggregates of metallacycles 3a,b and 4 upon the gradual addition of water to a THF solution containing metallacycles. Further studies indicated that these nanoaggregates were excellent probes for the sensitive and selective detection of nitro group containing picric acid (PA) derivatives as well as antibiotics.

Integrating radiomics with the vesical imaging-reporting and data system to predict muscle invasion of bladder cancer.

PURPOSE: To develop predictive models based on the integration of radiomics with the Vesical Imaging-Reporting and Data System (VI-RADS) for determining muscle invasion of bladder cancer. MATERIALS AND METHODS: One hundred ninety-one patients were retrospectively included in this study from January 2015 to March 2022. Of these, 121 data were randomly divided into training and validation sets at a ratio of 7:3. The remaining data (n = 70) served as the independent testing set. The radiomics features were extracted from bladder cancer on high-b-value DWI images. The pipelines of radiomics models were trained in the training set. One optimal model was selected based on the performance in the validation set. Then, the selected model was tested in the independent testing set. Two radiologists evaluated the VI-RADS based on T2WI and DWI. Reader 1 was an experienced reader, and Reader 2 was an inexperienced reader. A clinical-radiomics model was built by integrating the radiomics signature and VI-RADS. The performance was assessed using receiver operating characteristic curve analysis. The histopathological results were used as the standard reference to assess the diagnostic accuracy of muscle invasion. RESULTS: The radiomics model had area under the curve (AUC) values of 0.801, 0.867, and 0.806 in the training, validation, and testing sets, respectively. The VI-RADS scores of Readers 1/2 yielded AUC values of 0.831/0.781, 0.909/0.815, and 0.871/0.776 in the training, validation, and testing sets, respectively. The clinical-radiomics model for Readers 1/2 revealed AUC values of 0.889/0.854, 0.961/0.919, and 0.881/0.844 in the training, validation, and testing sets, respectively. The performance of the clinical-radiomics model was improved compared to the VI-RADS score for inexperienced Reader 2 (P < 0.05). CONCLUSION: The radiomics model was useful in the diagnosis of muscle invasion of bladder cancer. The clinical-radiomics model integrating radiomics and VI-RADS further improved the performance compared to VI-RADS alone, which was helpful for readers with less diagnostic experience.

Mathematical simulation of damage detection for fighting athletes and equipment based on conjugated polymer development.

Traditional combat sports equipment usually uses synthetic materials, such as polyurethane and synthetic leather. Although these materials have a certain degree of strength and durability, they have poor flexibility and antibacterial properties, making it difficult to provide stable support and protection for athletes. In order to enhance the antibacterial properties and flexibility of sports equipment and reduce the risk of injuries to athletes, this article conducts in-depth research on the development of combat sports equipment using conjugated polymers. This article first selects polypropylene (PP) as the base material for sports equipment for combat athletes, and uses the gas phase polymerization method to prepare the material; then uses chitosan as an antimicrobial agent and uses the oxidative degradation method to prepare it; after that, this article coats the chitosan antibacterial agent on the prepared PP material, and uses a combination of dipping and calendering for antibacterial treatment; finally, this article uses the spunbond melt-blown composite method to fill and combine the top equipment of combat athletes to achieve the structural design of sports equipment. In order to verify the effectiveness of the equipment, this article conducted equipment performance testing and sports injury simulation. The results showed that the average diameter of the antibacterial zone of this sports equipment reached more than 1 mm, and in the injury risk test, the risk of athletes' joint and muscle injuries was reduced by 16.9% and 20.5% respectively. Research shows that developing combat sports equipment based on conjugated polymers can help reduce the risk of injury to athletes and improve the safety of combat sports.

A Novel Huntington's Disease Assessment Platform to Support Future Drug Discovery and Development.

Huntington's disease (HD) is a lethal neurodegenerative disorder without efficient therapeutic options. The inefficient translation from preclinical and clinical research into clinical use is mainly attributed to the lack of (i) understanding of disease initiation, progression, and involved molecular mechanisms; (ii) knowledge of the possible HD target space and general data awareness; (iii) detailed characterizations of available disease models; (iv) better suitable models; and (v) reliable and sensitive biomarkers. To generate robust HD-like symptoms in a mouse model, the neomycin resistance cassette was excised from zQ175 mice, generating a new line: zQ175Δneo. We entirely describe the dynamics of behavioral, neuropathological, and immunohistological changes from 15-57 weeks of age. Specifically, zQ175Δneo mice showed early astrogliosis from 15 weeks; growth retardation, body weight loss, and anxiety-like behaviors from 29 weeks; motor deficits and reduced muscular strength from 36 weeks; and finally slight microgliosis at 57 weeks of age. Additionally, we collected the entire bioactivity network of small-molecule HD modulators in a multitarget dataset (HD_MDS). Hereby, we uncovered 358 unique compounds addressing over 80 different pharmacological targets and pathways. Our data will support future drug discovery approaches and may serve as useful assessment platform for drug discovery and development against HD.

Utility of diffusion weighted imaging-based radiomics nomogram to predict pelvic lymph nodes metastasis in prostate cancer.

BACKGROUND: Preoperative pelvic lymph node metastasis (PLNM) prediction can help clinicians determine whether to perform pelvic lymph node dissection (PLND). The purpose of this research is to explore the feasibility of diffusion-weighted imaging (DWI)-based radiomics for preoperative PLNM prediction in PCa patients at the nodal level. METHODS: The preoperative MR images of 1116 pathologically confirmed lymph nodes (LNs) from 84 PCa patients were enrolled. The subjects were divided into a primary cohort (67 patients with 192 positive and 716 negative LNs) and a held-out cohort (17 patients with 43 positive and 165 negative LNs) at a 4:1 ratio. Two preoperative pelvic lymph node metastasis (PLNM) prediction models were constructed based on automatic LN segmentation with quantitative radiological LN features alone (Model 1) and combining radiological and radiomics features (Model 2) via multiple logistic regression. The visual assessments of junior (Model 3) and senior (Model 4) radiologists were compared. RESULTS: No significant difference was found between the area under the curve (AUCs) of Models 1 and 2 (0.89 vs. 0.90; P = 0.573) in the held-out cohort. Model 2 showed the highest AUC (0.83, 95% CI 0.76, 0.89) for PLNM prediction in the LN subgroup with a short diameter ≤ 10 mm compared with Model 1 (0.78, 95% CI 0.70, 0.84), Model 3 (0.66, 95% CI 0.52, 0.77), and Model 4 (0.74, 95% CI 0.66, 0.88). The nomograms of Models 1 and 2 yielded C-index values of 0.804 and 0.910, respectively, in the held-out cohort. The C-index of the nomogram analysis (0.91) and decision curve analysis (DCA) curves confirmed the clinical usefulness and benefit of Model 2. CONCLUSIONS: A DWI-based radiomics nomogram incorporating the LN radiomics signature with quantitative radiological features is promising for PLNM prediction in PCa patients, particularly for normal-sized LNM.