Construction and Function of Thiolate-Bridged Diiron NxHy Nitrogenase Model Complexes.

ConspectusBiological nitrogen fixation mediated by nitrogenases has garnered significant research interest due to its critical importance to the development of efficient catalysts for mild ammonia synthesis. Although the active center of the most studied FeMo-nitrogenases has been determined to be a complicated [Fe7S9MoC] hetero-multinuclear metal-sulfur cluster known as the FeMo-cofactor, the exact binding site and reduction pathway of N2 remain a subject of debate. Over the past decades, the majority of studies have focused on mononuclear molybdenum or iron centers as potential reaction sites. In stark contrast, cooperative activation of N2 through bi- or multimetallic centers has been largely overlooked and underexplored, despite the renewed interest sparked by recent biochemical and computational studies. Consequently, constructing bioinspired bi- or multinuclear metallic model complexes presents an intriguing yet challenging prospect. In this Account, we detail our long-standing research on the design and synthesis of novel thiolate-bridged diiron complexes as nitrogenase models and their application to chemical simulations of potential biological N2 reduction pathways.Inspired by the structural and electronic features of the potential diiron active center in the belt region of the FeMo-cofactor, we have designed and synthesized a series of new thiolate-bridged diiron nitrogenase model complexes, wherein iron centers with +2 or +3 oxidation states are coordinated by Cp* as carbon-based donors and thiolate ligands as sulfur donors. Through the synergistic interaction between the two iron centers, unstable diazene (NH═NH) species can be trapped to generate the first example of a [Fe2S2]-type complex bearing a cis-µ-η1:η1-NH═NH subunit. Significantly, this species can not only catalyze the reductive N-N bond cleavage of hydrazine to ammonia but also trigger a stepwise reduction sequence NH═NH → [NH2-NH]- → [NH]2-(+NH3) → [NH2]- → NH3. Furthermore, an unprecedented thiolate-bridged diiron µ-nitride featuring a bent Fe-N-Fe moiety was successfully isolated and structurally characterized. Importantly, this diiron µ-nitride can undergo successive proton-coupled electron transfer processes to efficiently release ammonia in the presence of separate protons and electrons and can even be directly hydrogenated using H2 as a combination of protons and electrons for high-yield ammonia formation. Based on combined experimental and computational studies, we proposed two distinct reductive transformation sequences on the diiron centers, which involve a series of crucial NxHy intermediates. Moreover, we also achieved catalytic N2 reduction to silylamines with [Fe2S2]-type complexes by ligand modulation.Our bioinspired diiron cooperative scaffold may provide a suitable model for probing the potential N2 stepwise reduction pathways from the molecular level. Different from the traditional alternating and distal pathways dominated by mononuclear iron or molybdenum complexes, our proposed alternating transformation route based on the diiron centers may not involve the N2H4 intermediate, and the convergence point of the alternating and terminal pathways is imide, not amide. Our research strategy could inform the design and development of new types of bioinspired catalysts for mild and efficient nitrogen reduction in the future.

Randomized 20-year infancy-onset dietary intervention, life-long cardiovascular risk factors and retinal microvasculature.

BACKGROUND AND AIMS: Retinal microvasculature characteristics predict cardiovascular morbidity and mortality. This study investigated associations of lifelong cardiovascular risk factors and effects of dietary intervention on retinal microvasculature in young adulthood. METHODS: The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project study. The Special Turku Coronary Risk Factor Intervention Project is a 20-year infancy-onset randomized controlled dietary intervention study with frequent study visits and follow-up extending to age 26 years. The dietary intervention aimed at a heart-healthy diet. Fundus photographs were taken at the 26-year follow-up, and microvascular measures [arteriolar and venular diameters, tortuosity (simple and curvature) and fractal dimensions] were derived (n = 486). Cumulative exposure as the area under the curve for cardiovascular risk factors and dietary components was determined for the longest available time period (e.g. from age 7 months to 26 years). RESULTS: The dietary intervention had a favourable effect on retinal microvasculature resulting in less tortuous arterioles and venules and increased arteriolar fractal dimension in the intervention group when compared with the control group. The intervention effects were found even when controlled for the cumulative cardiovascular risk factors. Reduced lifelong cumulative intake of saturated fats, main target of the intervention, was also associated with less tortuous venules. Several lifelong cumulative risk factors were independently associated with the retinal microvascular measures, e.g. cumulative systolic blood pressure with narrower arterioles. CONCLUSIONS: Infancy-onset 20-year dietary intervention had favourable effects on the retinal microvasculature in young adulthood. Several lifelong cumulative cardiovascular risk factors were independently associated with retinal microvascular structure.

Two-Dimensional Transition Metal Phosphides As Cathode Additive in Robust Lithium-Sulfur Batteries.

The development of advanced cathode materials able to promote the sluggish redox kinetics of polysulfides is crucial to bringing lithium-sulfur batteries to the market. Herein, two electrode materials: namely, Zr2PS2 and Zr2PTe2, are identified through screening several hundred thousand compositions in the Inorganic Crystal Structure Database. First-principles calculations are performed on these two materials. These structures are similar to that of the classical MXenes. Concurrently, calculations show that Zr2PS2 and Zr2PTe2 possess high electrical conductivity, promote Li ion diffusion, and have excellent electrocatalytic activity for the Li-S reaction and particularly for the Li2S decomposition. Besides, the mechanisms behind the excellent predicted performance of Zr2PS2 and Zr2PTe2 are elucidated through electron localization function, charge density difference, and localized orbital locator. This work not only identifies two candidate sulfur cathode additives but may also serve as a reference for the identification of additional electrode materials in new generations of batteries, particularly in sulfur cathodes.

Enhancing the Thermoelectric and Mechanical Properties of p-Type PbS through Band Convergence and Microstructure Regulation.

While lead sulfide shows notable thermoelectric properties, its production costs remain high, and its mechanical hardness is low, which constrains its commercial viability. Herein, we demonstrate a straightforward and cost-effective method to produce PbS nanocrystals at ambient temperature. By introducing controlled amounts of silver, we achieve p-type conductivity and fine-tune the energy band structure and lattice configuration. Computational results show that silver shifts the Fermi level into the valence band, facilitating band convergence and thereby enhancing the power factor. Besides, excess silver is present as silver sulfide, which effectively diminishes the interface barrier and enhances the Seebeck coefficient. Defects caused by doping, along with dislocations and interfaces, reduce thermal conductivity to 0.49 W m-1 K-1 at 690 K. Moreover, the alterations in crystal structure and chemical composition enhance the PbS mechanical properties. Overall, optimized materials show thermoelectric figures of merit approximately 10-fold higher than that of pristine PbS, alongside an average hardness of 1.08 GPa.

Stepwise Reduction of Redox Noninnocent Nitrosobenzene to Aniline via a Rare Phenylhydroxylamino Intermediate on a Thiolate-Bridged Dicobalt Scaffold.

Nitrosobenzene (PhNO) and phenylhydroxylamine (PhNHOH) are of paramount importance because of their involvement as crucial intermediates in the biological metabolism and catalytic transformation of nitrobenzene (PhNO2) to aniline (PhNH2). However, a complete reductive transformation cycle of PhNO to PhNH2 via the PhNHOH intermediate has not been reported yet. In this context, we design and construct a new thiolate-bridged dicobalt scaffold that can accomplish coordination activation and reductive transformation of PhNO. Notably, an unprecedented reversible ligand-based redox sequence PhNO0 ↔ PhNO•- ↔ PhNO2- can be achieved on this well-defined {CoIII(µ-SPh)2CoIII} functional platform. Further detailed reactivity investigations demonstrate that the PhNO0 and PhNO•- complexes cannot react with the usual hydrogen and hydride donors to afford the corresponding phenylhydroxylamino (PhNHO-) species. However, the double reduced PhNO2- complex can readily undergo N-protonation with an uncommon weak proton donor PhSH to selectively yield a stable dicobalt PhNHO- bridged complex with a high pKa value of 13-16. Cyclic voltammetry shows that there are two successive reduction events at E1/2 = -0.075 V and Ep = -1.08 V for the PhNO0 complex, which allows us to determine both bond dissociation energy (BDEN-H) of 59-63 kcal·mol-1 and thermodynamic hydricity (ΔGH-) of 71-75 kcal·mol-1 of the PhNHO- complex. Both values indicate that the PhNO•- complex is not a potent hydrogen abstractor and the PhNO0 complex is not an efficient hydride acceptor. In the presence of BH3 as a combination of protons and electrons, facile N-O bond cleavage of the coordinated PhNHO- group can be realized to generate PhNH2 and a dicobalt hydroxide-bridged complex. Overall, we present the first stepwise reductive sequence, PhNO0 ↔ PhNO•- ↔ PhNO2- ↔ PhNHO- → PhNH2.

A Cyanine Dye for Highly Specific Recognition of Parallel G-Quadruplex Topology and Its Application in Clinical RNA Detection for Cancer Diagnosis.

G-quadruplex (G4), an unconventional nucleic acid structure, shows polymorphism in its topological morphology. The parallel G4 topology is the most prevalent form in organisms and plays a regulatory role in many biological processes. Designing fluorescent probes with high specificity for parallel G4s is important but challenging. Herein, a supramolecular assembly of the anionic cyanine dye SCY-5 is reported, which selectively identifies parallel G4 topology. SCY-5 can clearly distinguish parallel G4s from other G4s and non-G4s, even including hybrid-type G4s with parallel characteristics. The high specificity mechanism of SCY-5 involves a delicate balance between electrostatic repulsion and π-π interaction between SCY-5 and G4s. Using SCY-5, cellular RNA extracted from peripheral venous blood was quantitatively detected, and a remarkable increase in RNA G4 content in cancer patients compared to healthy volunteers was confirmed for the first time. This study provides new insights for designing specific probes for parallel G4 topology and opens a new path for clinical cancer diagnosis using RNA G4 as a biomarker.

Structural changes in the retina and serum HMGB1 levels are associated with decreased cognitive function in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a serious nonmotor symptom in patients with Parkinson's disease (PD). Currently, there are few studies investigating the relationship of serum markers and retinal structural changes with cognitive function in PD. OBJECTIVE: To investigate the relationship between retinal structural changes, serum high mobility group box-1 (HMGB1) levels and cognitive function and motor symptoms in PD patients. METHODS: Eighty-nine participants, including 47 PD patients and 42 healthy subjects, were enrolled. PD patients were divided into Parkinson's disease with normal cognitive (PD-NC), Parkinson's disease with mild cognitive impairment (PD-MCI), and Parkinson's disease with dementia (PDD) groups. The motor and nonmotor symptoms of PD patients were evaluated with clinical scale. Serum HMGB1 levels were detected by enzyme-linked immunosorbent assay (ELISA), and ganglion cell-inner plexiform layer complex (GCIPL) thickness changes in the macula were quantitatively analyzed by swept source optical coherence tomography (SS-OCT) in all patients. RESULTS: Compared with the control group, the macular GCIPL (t = -2.308, P = 0.023) was thinner and serum HMGB1 (z = -2.285, P = 0.022) was increased in PD patients. Macular GCIPL thickness in patients with PD-MCI and PDD were significantly lower than that in PD-NC patients, but there were no significant difference between the PD-MCI and PDD groups. Serum HMGB1 levels in patients with PD-MCI and PDD were significantly higher than those in PD-NC patients, and serum HMGB1 levels in PDD patients were higher than those in PD-MCI patients. Correlation analysis showed that serum HMGB1 levels in PD patients were positively correlated with disease duration, HY stage, UPDRS-I score, UPDRS-III score, and UPDRS total score and negatively correlated with MOCA score. Macular GCIPL thickness was negatively correlated with HY stage and positively correlated with MOCA score, and macular GCIPL thickness was negatively correlated with serum HMGB1 level. Logistic regression analysis showed that elevated serum HMGB1 level, thinner macular GCIPL thickness, and higher HY stage were independent risk factors for Parkinson's disease with cognitive impairment (PD-CI). The areas under the receiver operating characteristic curve (AUC) for the serum HMGB1 level and macular GCIPL thickness-based diagnosis of PD-MCI, PDD and PD-CI based on in patients with PD were 0.786 and 0.825, 0.915 and 0.856, 0.852 and 0.841, respectively. The AUC for the diagnosis of PD-MCI, PDD and PD-CI with serum HMGB1 level and GCIPL thickness combined were 0.869, 0.967 and 0.916, respectively. CONCLUSION: The macular GCIPL thickness and serum HMGB1 level are potential markers of cognitive impairment in PD patients, and their combination can significantly improve the accuracy of the diagnosis of cognitive impairment in PD.

Multiplex assays reveal anti-EBV antibody profile and its implication in detection and diagnosis of nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) is detected in nearly 100% of nonkeratinizing nasopharyngeal carcinoma (NPC) and EBV-based biomarkers are used for NPC screening in endemic regions. Immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA), and recently identified anti-BNLF2b antibodies have been shown to be the most effective screening tool; however, the screening efficacy still needs to be improved. This study developed a multiplex serological assay by testing IgA and immunoglobulin G (IgG) antibodies against representative EBV antigens that are highly transcribed in NPC and/or function crucially in viral reactivation, including BALFs, BNLF2a/b, LF1, LF2, and Zta (BZLF1). Among them, BNLF2b-IgG had the best performance distinguishing NPC patients from controls (area under the curve: 0.951, 95% confidence interval [CI]: 0.913-0.990). Antibodies to lytic antigens BALF2 and VCA were significantly higher in advanced-stage than in early-stage tumors; in contrast, antibodies to latent protein EBNA1 and early lytic antigen BNLF2b were not correlated with tumor progression. Accordingly, a novel strategy combining EBNA1-IgA and BNLF2b-IgG was proposed and validated improving the integrated discrimination by 15.8% (95% CI: 9.8%-21.7%, p < .0001) compared with the two-antibody method. Furthermore, we found EBV antibody profile in patients was more complicated compared with that in healthy carriers, in which stronger correlations between antibodies against different phases of antigens were observed. Overall, our serological assay indicated that aberrant latent infection of EBV in nasopharyngeal epithelial cells was probably a key step in NPC initiation, while more lytic protein expression might be involved in NPC progression.

Clinical findings of hyperechoic substantia nigra in patients with Parkinson's disease.

This study aims to analyse hyperechoic substantia nigra (HSN) characteristics and the correlation of HSN with clinical features and blood biomarkers in patients with Parkinson's disease (PD). Transcranial sonography (TCS) evaluations of the substantia nigra (SN) were performed in 40 healthy controls and 71 patients with PD, including patients with SN hyperechogenicity (SN+) and those with normal SN echogenicity (SN-). Evaluation of motor and non-motor symptoms was assessed by a series of rating scales. The uricase method was used to determine serum uric acid (UA) levels, and enzyme-linked immunosorbent assay (ELISA) was used to measure plasma interleukin (IL)-1ß levels. TCS showed 92.50% specificity and 61.97% sensitivity in differentiating PD patients from controls. The area of SN+ contralateral to the side of initial motor symptoms (SNcontra) was larger than that ipsilateral to the side of initial motor symptoms (SNipsi). The PDSN+ group had lower Argentine Hyposmia Rating Scale (AHRS) scores and UA levels than the PDSN- group. Binary logistic regression analysis revealed that AHRS scores and UA levels could be independent predictors for HSN. The larger SN echogenic area (SNL) sizes positively correlated with plasma IL-1ß levels in PD patients with SN+. The present study provides further evidence of the potential of SN echogenicity as an imaging biomarker for PD diagnosis. PD patients with HSN have more severe non-motor symptoms of hyposmia. HSN in PD patients is related to the mechanism of abnormal iron metabolism and microglial activation.

Increased plasma lipocalin-2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease.

Lipocalin-2 (LCN2) is essential for the regulation of neuroinflammation and cellular uptake of iron. This study aimed to evaluate plasma LCN2 levels and explore their correlation with clinical and neuroimaging features in Parkinson's disease (PD) patients. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma LCN2 levels in 120 subjects. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Voxel-based morphometry (VBM) was used to evaluate brain volume alterations, and quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in 46 PD patients. Plasma LCN2 levels were significantly higher in PD patients than those in healthy controls. LCN2 levels were negatively correlated with Montreal Cognitive Assessment (MoCA) scores, total brain gray matter volume (GMV), and GMV/total intracranial volume (TIV) ratio, but positively correlated with Hamilton Anxiety Rating Scale (HAMD) scores and mean QSM values of the bilateral substantial nigra (SN). Receiver operating characteristic (ROC) curves confirmed that plasma LCN2 levels had good predictive accuracy for PD. The results suggest that plasma LCN2 levels have potential as a biomarker for the diagnosis of PD. LCN2 may be a therapeutic target for neuroinflammation and brain iron deposition.

Diagnostic Value of Clear Cell Likelihood Score v1.0 and v2.0 for Common Subtypes of Small Renal Masses: A Multicenter Comparative Study.

BACKGROUND: Clear cell likelihood score (ccLS) is reliable for diagnosing small renal masses (SRMs). However, the diagnostic value of Clear cell likelihood score version 1.0 (ccLS v1.0) and v2.0 for common subtypes of SRMs might be a potential score extension. PURPOSE: To compare the diagnostic performance and interobserver agreement of ccLS v1.0 and v2.0 for characterizing five common subtypes of SRMs. STUDY TYPE: Retrospective. POPULATION: 797 patients (563 males, 234 females; mean age, 53 ± 12 years) with 867 histologically proven renal masses. FIELD STRENGTH/SEQUENCES: 3.0 and 1.5 T/T2 weighted imaging, T1 weighted imaging, diffusion-weighted imaging, a dual-echo chemical shift (in- and opposed-phase) T1 weighted imaging, multiphase dynamic contrast-enhanced imaging. ASSESSMENT: Six abdominal radiologists were trained in the ccLS algorithm and independently scored each SRM using ccLS v1.0 and v2.0, respectively. All SRMs had definite pathological results. The pooled area under curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the diagnostic performance of ccLS v1.0 and v2.0 for characterizing common subtypes of SRMs. The average κ values were calculated to evaluate the interobserver agreement of the two scoring versions. STATISTICAL TESTS: Random-effects logistic regression; Receiver operating characteristic analysis; DeLong test; Weighted Kappa test; Z test. The statistical significance level was P < 0.05. RESULTS: The pooled AUCs of clear cell likelihood score version 2.0 (ccLS v2.0) were statistically superior to those of ccLS v1.0 for diagnosing clear cell renal cell carcinoma (ccRCC) (0.907 vs. 0.851), papillary renal cell carcinoma (pRCC) (0.926 vs. 0.888), renal oncocytoma (RO) (0.745 vs. 0.679), and angiomyolipoma without visible fat (AMLwvf) (0.826 vs. 0.766). Interobserver agreement for SRMs between ccLS v1.0 and v2.0 is comparable and was not statistically significant (P = 0.993). CONCLUSION: The diagnostic performance of ccLS v2.0 surpasses that of ccLS v1.0 for characterizing ccRCC, pRCC, RO, and AMLwvf. Especially, the standardized algorithm has optimal performance for ccRCC and pRCC. ccLS has potential as a supportive clinical tool. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

TH-4000, a hypoxia-activated pan-HER inhibitor, shows excellent preclinical efficacy for the treatment of HER2+ breast cancer.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is correlated with poor prognosis, the current treatment of which is still based on surgery and adjuvant targeted therapy with monoclonal antibody. Problems of drug resistance hinder the use of monoclonal antibodies. Subsequently, tyrosine kinase inhibitors (TKIs) have been noticed, TKIs have the advantages of multi-targets and reduced drug resistance. However, TKIs that target HER family proteins often cause adverse effects such as liver damage and diarrhea. Thus, TKIs with high selectivity are being developed. TH-4000, a prodrug that generated an active form TH-4000Effector (TH-4000E) under hypoxic condition, was evaluated in this research. We found that TH-4000E ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium) (1-1000 nM) had potent and highly selective toxic effects on HER2+ breast cancer cells and inhibited the phosphorylation of HER family kinases at lower doses than that of Lapatinib and Tucatinib. TH-4000E activated Caspase-3 and induced apoptosis through a reactive oxygen species (ROS)-dependent pathway. The prodrug TH-4000 ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium;bromide) (50 mg/kg) effectively suppressed the tumor growth with less liver damage in mouse tumor models. This hypoxia-targeted strategy has possessed advantage in avoiding drug-induced liver damage, TH-4000 could be a promising drug candidate for the treatment of HER2+ breast cancer.

Preoperative evaluation of microvascular invasion in hepatocellular carcinoma with a radiological feature-based nomogram: a bi-centre study.

PURPOSE: To develop a nomogram for preoperative assessment of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on the radiological features of enhanced CT and to verify two imaging techniques (CT and MRI) in an external centre. METHOD: A total of 346 patients were retrospectively included (training, n = 185, CT images; external testing 1, n = 90, CT images; external testing 2, n = 71, MRI images), including 229 MVI-negative patients and 117 MVI-positive patients. The radiological features and clinical information of enhanced CT images were analysed, and the independent variables associated with MVI in HCC were determined by logistic regression analysis. Then, a nomogram prediction model was constructed. External validation was performed on CT (n = 90) and MRI (n = 71) images from another centre. RESULTS: Among the 23 radiological and clinical features, size, arterial peritumoral enhancement (APE), tumour margin and alpha-fetoprotein (AFP) were independent influencing factors for MVI in HCC. The nomogram integrating these risk factors had a good predictive effect, with AUC, specificity and sensitivity values of 0.834 (95% CI: 0.774-0.895), 75.0% and 83.5%, respectively. The AUC values of external verification based on CT and MRI image data were 0.794 (95% CI: 0.700-0.888) and 0.883 (95% CI: 0.807-0.959), respectively. No statistical difference in AUC values among training set and testing sets was found. CONCLUSION: The proposed nomogram prediction model for MVI in HCC has high accuracy, can be used with different imaging techniques, and has good clinical applicability.

A quantitative analysis of the improvement provided by comprehensive annotation on CT lesion detection using deep learning.

BACKGROUND: Data collected from hospitals are usually partially annotated by radiologists due to time constraints. Developing and evaluating deep learning models on these data may result in over or under estimation PURPOSE: We aimed to quantitatively investigate how the percentage of annotated lesions in CT images will influence the performance of universal lesion detection (ULD) algorithms. METHODS: We trained a multi-view feature pyramid network with position-aware attention (MVP-Net) to perform ULD. Three versions of the DeepLesion dataset were created for training MVP-Net. Original DeepLesion Dataset (OriginalDL) is the publicly available, widely studied DeepLesion dataset that includes 32 735 lesions in 4427 patients which were partially labeled during routine clinical practice. Enriched DeepLesion Dataset (EnrichedDL) is an enhanced dataset that features fully labeled at one or more time points for 4145 patients with 34 317 lesions. UnionDL is the union of the OriginalDL and EnrichedDL with 54 510 labeled lesions in 4427 patients. Each dataset was used separately to train MVP-Net, resulting in the following models: OriginalCNN (replicating the original result), EnrichedCNN (testing the effect of increased annotation), and UnionCNN (featuring the greatest number of annotations). RESULTS: Although the reported mean sensitivity of OriginalCNN was 84.3% using the OriginalDL testing set, the performance fell sharply when tested on the EnrichedDL testing set, yielding mean sensitivities of 56.1%, 66.0%, and 67.8% for OriginalCNN, EnrichedCNN, and UnionCNN, respectively. We also found that increasing the percentage of annotated lesions in the training set increased sensitivity, but the margin of increase in performance gradually diminished according to the power law. CONCLUSIONS: We expanded and improved the existing DeepLesion dataset by annotating additional 21 775 lesions, and we demonstrated that using fully labeled CT images avoided overestimation of MVP-Net's performance while increasing the algorithm's sensitivity, which may have a huge impact to the future CT lesion detection research. The annotated lesions are at https://github.com/ComputationalImageAnalysisLab/DeepLesionData.

Remote Sensing Image Classification Based on Canny Operator Enhanced Edge Features.

Remote sensing image classification plays a crucial role in the field of remote sensing interpretation. With the exponential growth of multi-source remote sensing data, accurately extracting target features and comprehending target attributes from complex images significantly impacts classification accuracy. To address these challenges, we propose a Canny edge-enhanced multi-level attention feature fusion network (CAF) for remote sensing image classification. The original image is specifically inputted into a convolutional network for the extraction of global features, while increasing the depth of the convolutional layer facilitates feature extraction at various levels. Additionally, to emphasize detailed target features, we employ the Canny operator for edge information extraction and utilize a convolution layer to capture deep edge features. Finally, by leveraging the Attentional Feature Fusion (AFF) network, we fuse global and detailed features to obtain more discriminative representations for scene classification tasks. The performance of our proposed method (CAF) is evaluated through experiments conducted across three openly accessible datasets for classifying scenes in remote sensing images: NWPU-RESISC45, UCM, and MSTAR. The experimental findings indicate that our approach based on incorporating edge detail information outperforms methods relying solely on global feature-based classifications.

[Comparison of effectiveness of long and short proximal femoral nail anti-rotation in treatment of type A2.3 intertrochanteric fracture of femur].

Objective: To compare the effectiveness of long and short proximal femoral nail anti-rotation (PFNA) in the treatment of type A2.3 intertrochanteric fracture of femur (IFF). Methods: The clinical data of 54 patients with type A2.3 IFF admitted between January 2020 and December 2022 were retrospectively analyzed. According to the length of PFNA nail used in the operation, they were divided into long nail group (PFNA nail length>240 mm, 24 cases) and short nail group (PFNA nail length≤240 mm, 30 cases). There was no significant difference in baseline data such as gender, age, fracture side, body mass index, and time from fracture to operation between the two groups ( P>0.05). The operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, intraoperative reduction quality score, fracture healing, and complications of the two groups were recorded and compared. Harris score was used to evaluate the hip function of patients at 1 year after operation. According to the relationship between the fracture line of type A2.3 IFF and the lesser trochanter, the two groups of patients were divided into type Ⅰ(the fracture line extends to the level of the lesser trochanter), type Ⅱ(the fracture line extends to less than 2 cm below the lesser trochanter), and type Ⅲ (the fracture line extends to more than 2 cm below the lesser trochanter), and the postoperative stability and internal fixator loosening of each subtype were evaluated. Results: The operation time, intraoperative blood loss, and intraoperative fluoroscopy frequency in short nail group were significantly less than those in long nail group ( P<0.05). There was no significant difference in the intraoperative reduction quality score between the two groups ( P>0.05). Patients in both groups were followed up 12-18 months, with an average of 13.5 months. The postoperative stability score of short nail group was significantly lower than that of long nail group ( P<0.05). The Harris score in the long nail group was significantly higher than that in the short nail group at 1 year after operation ( P<0.05), but there was no significant difference in Harris score grading between the two groups ( P>0.05). Complications occurred in 3 cases of the long nail group (including 1 case of coxa varus caused by external nail entry point and 2 cases of loose internal fixator), and 7 cases of the short nail group (including 1 case of coxa varus caused by external nail entry point and 6 cases of loose internal fixator). Neither group had any anterior femoral arch damage, there was no significant difference in the incidence of complications between the two groups ( P>0.05). The number of type Ⅲ patients was relatively small and not included in the statistics; there was no significant difference in the postoperative stability score and the incidence of internal fixator loosening between the long and short nail groups in type Ⅰ patients ( P>0.05). In type Ⅱ patients, the postoperative stability score and the incidence of internal fixation loosening in the long nail group were significantly better than those in the short nail group ( P<0.05). Conclusion: Long PFNA fixation for type A2.3 IFF has longer operation time and more intraoperative blood loss, but the overall stability of fracture is better after operation. For type A2.3 IFF with fracture line extending to less than 2 cm below the lesser trochanter, long PFNA is used for fixation, although the surgical trauma is large, but the postoperative stability is better than that of short PFNA; for type A2.3 IFF with fracture line extending to the lesser trochanter, there is no significant difference in postoperative stability between long and short PFNAs.

Exercise may not just be good for sleep; It can also help lower cardiovascular event risk.

Cardiovascular diseases (CVD) stand at the forefront of global mortality, presenting an immense and urgent public health challenge on a global scale. Effectively addressing the associated risk factors is pivotal in not only preventing but also stabilizing and potentially reversing the progression of these conditions. Emerging research illuminates a compelling correlation between sleep disorders and CVD. Clinically, individuals afflicted with existing CVD or those possessing risk factors frequently grapple with sleep disturbances, exacerbating their conditions, particularly in severe cases where disease progression is accelerated. Even among ostensibly healthy individuals, chronic sleep deprivation exacts a toll on cardiovascular function. The strategic implementation of exercise interventions emerges as a potent tool in enhancing sleep quality, surpassing the efficacy of pharmaceutical treatments. Furthermore, the maintenance of optimal sleep patterns significantly contributes to lowering the risk of cardiovascular diseases. This comprehensive review delves deeply into the intricate relationship between exercise and the amelioration of cardiovascular disease risk associated with sleep. Moreover, it meticulously elucidates the complex mechanisms through which exercise operates, effectively reducing cardiovascular disease risk from the unique perspective of sleep science.

Mitochondrial dysfunction in type 2 diabetes: A neglected path to skeletal muscle atrophy.

Over the course of several decades, robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes. However, the specific intricacies governing this process remain elusive. Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation. Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.

Superiority of spleen stiffness on two-dimensional magnetic resonance elastography over liver stiffness and serum tests in assessing portal hypertension in chronic liver disease.

Background: The value of magnetic resonance elastography (MRE) in portal hypertension (PH) has yet to be determined in the context of chronic liver disease (CLD). This study examined the value of MRE for the prediction of hepatic venous pressure gradient (HVPG) and high-risk esophageal varices (EVs) in a CLD cohort with a generally high HVPG. Methods: Patients with CLD who underwent both HVPG measurement and two-dimensional MRE examination at Beijing Friendship Hospital between April 2018 and March 2022 were prospectively included. Two-dimensional MRE was performed within the liver and spleen. Endoscopy results and laboratory parameters were collected. Some selected published serum markers were calculated, including fibrosis 4, aspartate aminotransferase-to-platelet ratio index, and King's score. The efficacy of the parameters for assessing PH was analyzed by using the Pearson correlation coefficient, linear and logistic regression, and receiver operating characteristic curve analyses. Results: A total of 48 patients were included. The mean HVPG was 16.8±5.8 mmHg. Among these patients, 47 patients had PH (HVPG >5 mmHg), and 43 patients had clinically significant PH (HVPG ≥10 mmHg). Among the parameters associated with HVPG, the strongest correlation was found for spleen stiffness (SS) (R=0.638; P<0.001). In multiple regression analyses, SS was independently associated with an elevated HVPG and high-risk EVs. The areas under the receiver operating characteristic curve of SS for identifying patients with an HVPG ≥16 mmHg, HVPG ≥20 mmHg, and high-risk EVs were 0.790, 0.822, and 0.886, respectively, which were higher than those of liver stiffness (LS) and serum markers but slightly inferior to that of fibrosis 4 (area under the receiver operating characteristic curve =0.844) in identifying an HVPG ≥16 mmHg. SS cutoff values of 9.5, 10.05, and 9.9 kPa were selected to rule out the presence of an HVPG ≥16 mmHg, HVPG ≥20 mmHg, and high-risk EVs (sensitivity: 100%, 100%, and 100%, respectively; specificity: 45.5%, 50%, and 60%, respectively). Conclusions: In patients with generally high HVPG, SS measured by two-dimensional MRE may be a better predictor of HVPG values and high-risk EVs than LS and serum markers.