Tri-Compartmental Restriction Spectrum Imaging Based on 18F-FDG PET/MR for Identification of Primary Benign and Malignant Lung Lesions.

BACKGROUND: Restriction spectrum imaging (RSI), as an advanced quantitative diffusion-weighted magnetic resonance imaging technique, has the potential to distinguish primary benign and malignant lung lesions. OBJECTIVE: To explore how well the tri-compartmental RSI performs in distinguishing primary benign from malignant lung lesions compared with diffusion-weighted imaging (DWI), and to further explore whether positron emission tomography/magnetic resonance imaging (PET/MRI) can improve diagnostic efficacy. STUDY TYPE: Prospective. POPULATION: 137 patients, including 108 malignant and 29 benign lesions (85 males, 52 females; average age = 60.0 ± 10.0 years). FIELD STRENGTH/SEQUENCE: T2WI, T1WI, multi-b value DWI, MR-based attenuation correction, and PET imaging on a 3.0 T whole-body PET/MR system. ASSESSMENT: The apparent diffusion coefficient (ADC), RSI-derived parameters (restricted diffusion f 1 $$ {f}_1 $$ , hindered diffusion f 2 $$ {f}_2 $$ , and free diffusion f 3 $$ {f}_3 $$ ) and the maximum standardized uptake value (SUVmax) were calculated and analyzed for diagnostic efficacy individually or in combination. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, receiver operating characteristic (ROC) curves, Delong test, Spearman's correlation analysis. P < 0.05 was considered statistically significant. RESULTS: The f 1 $$ {f}_1 $$ , SUVmax were significantly higher, and f 3 $$ {f}_3 $$ , ADC were significantly lower in the malignant group [0.717 ± 0.131, 9.125 (5.753, 13.058), 0.194 ± 0.099, 1.240 (0.972, 1.407)] compared to the benign group [0.504 ± 0.236, 3.390 (1.673, 6.030), 0.398 ± 0.195, 1.485 ± 0.382]. The area under the ROC curve (AUC) values ranked from highest to lowest as follows: AUC (SUVmax) > AUC ( f 3 $$ {f}_3 $$ ) > AUC ( f 1 $$ {f}_1 $$ ) > AUC (ADC) > AUC ( f 2 $$ {f}_2 $$ ) (AUC = 0.819, 0.811, 0.770, 0.745, 0549). The AUC (AUC = 0.900) of the combined model of RSI with PET was significantly higher than that of either single-modality imaging. CONCLUSION: RSI-derived parameters ( f 1 $$ {f}_1 $$ , f 3 $$ {f}_3 $$ ) might help to distinguish primary benign and malignant lung lesions and the discriminatory utility of f 2 $$ {f}_2 $$ was not observed. The RSI exhibits comparable or potentially enhanced performance compared with DWI, and the combined RSI and PET model might improve diagnostic efficacy. TECHNICAL EFFICACY: Stage 2.

Improved Photovoltaic Performance of Inverted Two-Dimensional Perovskite Solar Cells via a Simple Molecular Bridge on Buried Interface.

NiOx-based two-dimensional perovskite solar cells (2D-PSCs) have the advantages of low fabrication temperature, suitable energy level matching, suppressed hysteresis, and superior stability, while the poor interfacial contacts between NiOx and perovskite layers limit the perovskite film growth and charge transfer. Herein, a simple molecule, urea, was used as a molecular modifier to form bifacial passivation on the buried interface of NiOx/perovskite, resulting in better interfacial contact and efficient bifacial passivation. We demonstrated that efficient bifacial passivation mainly comes from strong interactions between urea and NiOx or perovskite, which make urea a molecular bridge for smoother charge transfer. Moreover, urea can regulate the ratio of Ni3+/Ni2+, therefore boosting the conductivity of NiOx, and adjust the morphology of the NiOx film for better 2D-perovskite crystal growth. Besides, urea also passivates the bifacial defect states of both NiOx and perovskite film, yielding reduced defect density of the perovskite film and superior charge transfer on the buried interface. Consequently, inverted 2D-PSCs with urea modification proved significant improvements in short-circuit current density and fill factor, resulting in improved power conversion efficiency from 14.64 to 16.84% with better stability in air.

Phosphorescent fac-Bis(triarylisocyanide) W(0) and Mo(0) Complexes.

Homoleptic W(0) and Mo(0) complexes containing bis(triarylisocyanide) ligands with bulky substituents were synthesized and spectroscopically characterized. Crystallographically determined structures revealed that these complexes are hourglass-like in shape with the tridentate ligands adopting a facial coordination mode to the metal center. These complexes luminesce in fluid solutions and in the solid state. Typically in toluene at 298 K, the two W(0) complexes display the emission maximum (lifetime and quantum yield) at 591 nm (0.83 µs and 0.35) and 628 nm (1.04 µs and 0.39), and similarly, the two Mo(0) complexes display it at 575 nm (0.54 µs and 0.15) and 617 nm (0.56 µs and 0.23). DFT and TDDFT calculations indicated that the low-energy absorption bands of the W(0) and Mo(0) complexes could be metal-to-ligand charge transfer (MLCT) transitions in nature. These complexes exhibited a reversible M+/0 redox couple at -0.70 and -0.63 V vs Fc+/0 for the W(0) complexes and -0.86 and -0.67 V for the Mo(0) complexes. The excited-state reduction potentials were hence estimated to be -2.91 and -2.74 V vs Fc+/0 for the W(0) complexes and -3.10 and -2.81 V vs Fc+/0 for the Mo(0) complexes, indicating that they are potentially strong photoreductants.

Gene variants and clinical characteristics of children with sitosterolemia.

OBJECTIVE: To enhance the detection, management and monitoring of Chinese children afflicted with sitosterolemia by examining the physical characteristics and genetic makeup of pediatric patients. METHODS: In this group, 26 children were diagnosed with sitosterolemia, 24 of whom underwent genetic analysis. Patient family medical history, physical symptoms, tests for liver function, lipid levels, standard blood tests, phytosterol levels, cardiac/carotid artery ultrasounds, fundus examinations, and treatment were collected. RESULTS: The majority (19, 73.1%) of the 26 patients exhibited xanthomas as the most prevalent manifestation. The second most common symptoms were joint pain (7, 26.9%) and stunted growth (4, 15.4%). Among the 24 (92.3%) patients whose genetics were analyzed, 16 (66.7%) harbored ABCG5 variants (type 2 sitosterolemia), and nearly one-third (8, 33.3%) harbored ABCG8 variants (type 1 sitosterolemia). Additionally, the most common pathogenic ABCG5 variant was c.1166G > A (p.Arg389His), which was found in 10 patients (66.7%). Further analysis did not indicate any significant differences in pathological traits among those carrying ABCG5 and ABCG8 variations (P > 0.05). Interestingly, there was a greater abundance of nonsense variations in ABCG5 than in ABCG8 (P = 0.09), and a greater frequency of splicing variations in ABCG8 than ABCG5 (P = 0.01). Following a change in diet or a combination of ezetimibe, the levels of cholesterol and low-density lipoprotein were markedly decreased compared to the levels reported before treatment. CONCLUSION: Sitosterolemia should be considered for individuals presenting with xanthomas and increased cholesterol levels. Phytosterol testing and genetic analysis are important for early detection. Managing one's diet and taking ezetimibe can well control blood lipids.

Automatic segmentation of the interscapular brown adipose tissue in rats based on deep learning using the dynamic magnetic resonance fat fraction images.

OBJECTIVE: The study aims to propose an accurate labelling method of interscapular BAT (iBAT) in rats using dynamic MR fat fraction (FF) images with noradrenaline (NE) stimulation and then develop an automatic iBAT segmentation method using a U-Net model. MATERIALS AND METHODS: Thirty-four rats fed different diets or housed at different temperatures underwent successive MR scans before and after NE injection. The iBAT were labelled automatically by identifying the regions with obvious FF change in response to the NE stimulation. Further, these FF images along with the recognized iBAT mask images were used to develop a deep learning network to accomplish the robust segmentation of iBAT in various rat models, even without NE stimulation. The trained model was then validated in rats fed with high-fat diet (HFD) in comparison with normal diet (ND). RESULT: A total of 6510 FF images were collected using a clinical 3.0 T MR scanner. The dice similarity coefficient (DSC) between the automatic and manual labelled results was 0.895 ± 0.022. For the network training, the DSC, precision rate, and recall rate were found to be 0.897 ± 0.061, 0.901 ± 0.068 and 0.899 ± 0.086, respectively. The volumes and FF values of iBAT in HFD rats were higher than ND rats, while the FF decrease was larger in ND rats after NE injection. CONCLUSION: An automatic iBAT segmentation method for rats was successfully developed using the dynamic labelled FF images of activated BAT and deep learning network.

Orthopedic manifestations in children with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare genetic disease often associated with bone problems, mainly scoliosis and hip dysplasia (HD). This study aimed to analyze the clinical characteristics of orthopedic deformities in patients with PWS. METHODS: A retrospective study was conducted on 175 patients up to March 2023. The Cobb angle(CA) of the spine, the alpha angle of the hip joint, and the acetabular index (AI) were measured. This study aimed to evaluate the relationship between demographic parameters and bone deformities. RESULTS: Scoliosis was found in 66 patients (43.7%), including 52 (78.8%) with mild scoliosis, 10 (15.2%) with moderate scoliosis, and 4 (6.1%) with severe scoliosis. Only seven patients received orthopedic treatment (10.6%). The median age of scoliosis was 4.5 years old, and the prevalence of scoliosis increased rapidly at the age of 5 years and adolescence. The mean CA in this study increased gradually with age. HD was found in 47 patients (38.2%), and 6 patients received orthopedic treatment (12.7%). The median age at HD was 1.8 years old. The mean AI of the study population decreased with age. The prevalence of HD treated with recombinant human growth hormone (rhGH) was low. No significant differences were observed in sex, genotype, body mass index (BMI), obesity rate, or onset of scoliosis and HD. CONCLUSION: The prevalence of scoliosis and HD was higher in patients with PWS. The onset age and developmental trends of the different skeletal malformations were different. Early diagnosis and treatment are important for the prognosis and treatment of orthopedic diseases in patients with PWS.

Reducing the ambiguity of field inhomogeneity and chemical shift effect for fat-water separation by field factor.

PURPOSE: To reduce the ambiguity between chemical shift and field inhomogeneity with flexible TE combinations by introducing a variable (field factor). THEORY AND METHODS: The ambiguity between chemical shift and field inhomogeneity can be eliminated directly from the multiple in-phase images acquired at different TEs; however, it is only applicable to few echo combinations. In this study, we accommodated such an implementation in flexible TE combinations by introducing a new variable (field factor). The effects of the chemical shift were removed from the field inhomogeneity in the candidate solutions, thus reducing the ambiguity problem. To validate this concept, multi-echo MRI data acquired from various anatomies with different imaging parameters were tested. The derived fat and water images were compared with those of the state-of-the-art fat-water separation algorithms. RESULTS: Robust fat-water separation was achieved with the accurate solution of field inhomogeneity, and no apparent fat-water swap was observed. In addition to the good performance, the proposed method is applicable to various fat-water separation applications, including different sequence types and flexible TE choices. CONCLUSION: We propose an algorithm to reduce the ambiguity of chemical shift and field inhomogeneity and achieved robust fat-water separation in various applications.

A 5-channel local B0 shimming coil combined with a 3-channel RF receiver coil for rat brain imaging at 3 T.

PURPOSE: We aimed to improve B0 magnetic field homogeneity and minimize the interference between RF coils and local B0 shimming coils with few channel numbers. METHODS: To design and construct the prototype for B0 shimming of the rat brain, we first evaluated the interferences of single shimming loops on RF receiver loops. Then, B0 shimming of the whole rat brain was implemented using an optimization procedure. The positions and currents of the local shimming coils with channel numbers from 3 to 6 were optimized to improve shimming performance. Based on the simulation results, a 5-channel local shimming coil, combined with a 3-channel RF receiver coil, was constructed and evaluated by animal experiments. RESULTS: There was marginal SNR loss within 5% after integrating the local shimming coil into the RF receiver coil. With respect to the Siemens standard shims up to second order, the B0 inhomogeneity in one whole rat brain was reduced from 39.6 Hz to 24.7 Hz by using the local shimming coil. A large portion of the EPI distortions was recovered after using the 5-channel local shimming coil. The temporal SNR using the local shimming coil was higher than that using the Siemens standard shims up to second order, with an improvement of more than 24%. CONCLUSIONS: The local shimming coil can improve B0 magnetic field homogeneity despite minor effects on the RF coil and can benefit a variety of applications that are sensitive to B0 inhomogeneity. Nevertheless, EPI for rat brain is still very challenging.

A new deuterium-labeled compound [2,3,4,6,6'-2 H5 ]-D-glucose for deuterium magnetic resonance metabolic imaging.

Deuterium (2 H) magnetic resonance imaging is an emerging approach for noninvasively studying glucose metabolism in vivo, which is important for understanding pathogenesis and monitoring the progression of many diseases such as tumors, diabetes, and neurodegenerative diseases. However, the synthesis of 2 H-labeled glucose is costly because of the expensive raw substrates and the requirement for extreme reaction conditions, making the 2 H-labeled glucose rather expensive and unaffordable for clinic use. In this study, we present a new deuterated compound, [2,3,4,6,6'-2 H5 ]-D-glucose, with an approximate 10-fold reduction in production costs. The synthesis route uses cheaper raw substrate methyl-α-D-glucopyranoside, relies on mild reaction conditions (80°C), and has higher deuterium labeling efficiency. Magnetic resonance spectroscopy (MRS) and mass spectroscopy experiments confirmed the successful deuterium labeling in the compound. Animal studies demonstrated that the substrate could describe the glycolytic metabolism in a glioma rat model by quantifying the downstream metabolites through 2 H-MRS on an ultrahigh field system. Comparison of the glucose metabolism characteristics was carried out between [2,3,4,6,6'-2 H5 ]-D-glucose and commercial [6,6'-2 H2 ]-D-glucose in the animal studies. This cost-effective compound will help facilitate the clinical translation of deuterium magnetic resonance imaging, and enable this powerful metabolic imaging modality to be widely used in both preclinical and clinical research and applications.

Fatty Acids Composition of the Sacroiliac Joint in Axial Spondyloarthritis: Analysis Using 3.0 T Chemical Shift-Encoded MRI.

BACKGROUND: Axial spondyloarthritis (axSpA) is a group of inflammatory diseases that may lead to ankylosis of the sacroiliac joint and spine. Fat lesion in the sacroiliac joint is an important feature in diagnosis and disease progression of axSpA. However, whether there is alteration of fatty acids (FAs) composition has not been investigated using MRI. PURPOSE: To investigate bone marrow FA composition of the sacroiliac joint in patients with axSpA compared to controls. STUDY TYPE: Prospective. SUBJECTS: Eighty five participants (mean age, 32.3 ± 6.1 years): 48 axSpA (25 male, 23 female) and 37 non-SpA controls (18 male, 19 female). FIELD STRENGTH/SEQUENCE: 3.0 T/Two multiple gradient-echo chemical shift-encoded (CSE) MRI which differed only in echo times (TEs) were scanned consecutively. ASSESSMENT: Axial multi-echo CSE MRI was performed in the sacroiliac joints in vivo. Regions of interest (ROIs) were manually placed on subchondral bone with and without fat lesion in axSpA patients, and on subchondral bone without fat lesion in controls. FA composition was computed within the ROIs using a nonlinear least square method from literature. STATISTICAL TESTS: Intergroup comparisons were performed using t tests. RESULTS: In axSpA, male patients had significantly higher monounsaturated FA compared to controls in areas with fat lesion in the sacrum (+12%) and in the ilium (+9%), and in areas without fat lesion in the sacrum (+10%). Significantly lower polyunsaturated FAs were found in areas with fat lesion in the sacrum (-10%) and ilium (-11%), and lower saturated FAs were found in areas without fat lesion in the sacrum (-6%). In female, patients with axSpA had significantly higher saturated FAs in areas with fat lesion in the ilium (+7%) in comparison to controls. DATA CONCLUSION: FA composition of the sacroiliac joint alters in patients with axSpA, and it can be detected using CSE MRI based analysis.

Tunable Yellow to Near-Infrared Fluorescent Boron-Amino-Chelating Complexes with Stokes Shifts >100 nm.

A series of diphenylboron-chelating N-substituent 8-aminoquinoline, 5-aminoquinoxaline, and 1-aminophenazine were prepared. They exhibit lowest energy absorption peaks of 444-766 nm, emission peaks of 563-820 nm, and quantum yields of up to 46.5%. Electrochemical and theoretical studies indicate that the N-substituent mainly determines the HOMO and the framework determines the LUMO, thus allowing for a wide-tuning of absorptions/emissions. Intramolecular charge transfer transition leads to large Stokes shifts of up to 166 nm. One selected compound showed satisfactory cytocompatibility and cytoplasm-targeting cell imaging ability.

Dicationic Diimine Pt(II) Bis(N-heterocyclic allenylidene) Complexes: Extended Pt···Pt Chains, NIR Phosphorescence, and Chromonics.

Although square-planar Pt(II) complexes are well-known to self-assemble into supramolecules via noncovalent intermolecular Pt···Pt and/or π-π interactions, the self-assembly of dicationic Pt(II) complexes was scarce due to the electrostatic repulsive force. Herein, a series of dicationic diimine bis(N-heterocyclic allenylidene) Pt(II) complexes were synthesized and characterized. Close Pt···Pt and/or π-π contacts are observed in the crystals of these complexes. In particular, complexes 1·2PF6 and 2·2PF6 exhibit one-dimensional packing with extended Pt···Pt contacts of 3.302 and 3.240 Å, respectively. The photophysical properties of these complexes in the solution and solid state were investigated. NIR emission was recorded for complexes 1·2PF6 (λmax = 950 nm) and 2·2PF6 (λmax = 855 nm) in the solid state at 298 K. To explore the aggregate behaviors of these complexes, the counteranion PF6- was exchanged to the large lipophilic anion 2,3,4-tris(dodecyloxy)benzene sulfonate (LA-) and the hydrophilic anion Cl-. Complexes 1·2LA and 2·2LA or 1·2Cl and 2·2Cl could self-assemble with Pt···Pt and/or π-π interactions in the nonpolar or aqueous solutions as well. Further increasing the concentration of 1·2Cl and 2·2Cl in aqueous solution, chromonic mesophases with NIR emission (λmax = 988 nm) were obtained. DFT and TD-DFT calculations were performed to gain deep insight into the dication-dication packings and photophysical properties of the complexes. The σ-donating as well as π-accepting character of the N-heterocyclic allenylidene ligand endows complexes with rigid and electron-delocalized coplanar features, which are conducive to achieving the self-assembling processes associated with Pt···Pt and/or π-π interactions.

Effects of different cathodic potentials on performance, microbial community structure and function for bioelectrochemical-stimulated dechlorination of 2,4,6-trichlorophenol in sediments.

Bioelectrochemical systems with biocathodes constitute a promising means to enhance the biological dechlorination of 2,4,6-trichlorophenol (2,4,6-TCP) in constructed wetland (CW) sediments. However, the effect of different cathodic potentials on the structure and function of 2,4,6-TCP-reducing biocathode communities in CW sediments is largely unknown. Here, we evaluated the performance and microbial community structure of 2,4,6-TCP-reducing biocathode systems at different cathodic potentials (- 0.5, - 0.7, - 0.9, and - 1.1 V vs. saturated calomel electrode). The dechlorination efficiency of 2,4,6-TCP with the biocathode relatively increased by 16.02%-33.17% compared to that in the open circuit. The highest 2,4,6-TCP dechlorination efficiency (92.34 ± 0.86%) was observed at - 0.7 V in sediment, which may be due to the highest abundance of functional genera (e.g., Pseudomonas, Spirochaeta) at - 0.7 V. Metagenomic analysis provided new insights into the metabolic potential of microorganisms in CW sediments and suggested possible 2,4,6-TCP conversion pathways in sediments. 2,4,6-TCP was gradually dechlorinated to form 4-chlorophenol, followed by a ring-opening step via the activities of chlorophenol reductive dehalogenase and oxygenase (e.g., cprA, tfdB). Interestingly, micro-electrical stimulation enhanced the expression of chlorophenol reductive dehalogenase (cprA). Therefore, our findings at the molecular and gene expression levels provide insights into the effects of different cathodic potentials on the performance and community structure of 2,4,6-TCP-reducing biocathode systems in CW sediments.

Automatic segmentation of human supraclavicular adipose tissue using high-resolution T2-weighted magnetic resonance imaging.

OBJECTIVE: To achieve efficient segmentation of human supraclavicular adipose tissue (sclavAT) using high-resolution T2-weighted magnetic resonance images. METHODS: High-resolution 1.0 mm isotropic 3D T2-weighted images covering human supraclavicular area were acquired in transverse or coronary plane from 29 volunteers using a 3.0 T MRI scanner. There were typically 144/288 slices for the transverse/coronary scans for each subject, which amounts to a total of 6816 images in 29 volunteers. A U-NET network was trained to segment the supraclavicular adipose tissue (sclavAT). The performance of the automatic segmentation method was evaluated by comparing the output results with the manual labels using the quantitative indices of dice similarity coefficient (DSC), precision rate (PR), and recall rate (RR). The auto-segmented images were used to calculate the sclavAT volumes and registered to the MR fat fraction (FF) images to quantify the fat component of the sclavAT area. The relationship between body mass index (BMI), the volume and FF of sclavAT area was evaluated for all subjects. RESULTS: The DSC, PR and RR of the automatic sclavAT segmentation method on the testing datasets were 0.920 ± 0.048, 0.915 ± 0.070 and 0.930 ± 0.058. The volume and the mean FF of sclavAT were both found to be strongly correlated to BMI, with the correlation coefficient of 0.703 and 0.625 (p < 0.05), respectively. The averaged computation time of the automatic segmentation method was approximately 0.06 s per slice, compared to more than 5 min for manual labeling. CONCLUSION: The present study demonstrates that the proposed automatic segmentation method using U-Net network is able to identify human sclavAT efficiently and accurately.

CircRRAS2 promotes myogenic differentiation of bovine MuSCs and is a novel regulatory molecule of muscle development.

The proliferation and myogenic differentiation of muscle stem cells (MuSCs) are important factors affecting muscle development and beef quality. There is increasing evidence that circRNAs can regulate myogenesis. We found a novel circRNA, named circRRAS2 that is significantly upregulated in the differentiation phase of bovine MuSCs. Here, we aimed to determine its roles in the proliferation and myogenic differentiation of these cells. The results showed that circRRAS2 was expressed in several bovine tissues. CircRRAS2 inhibited MuSCs proliferation and promoted myoblast differentiation. In addition, chromatin isolation by using RNA purification and mass spectrometry in differentiated muscle cells identified 52 RNA-binding proteins that could potentially bind to circRRAS2, in order to regulate their differentiation. The results suggest that circRRAS2 could be a specific regulator of myogenesis in bovine muscle.HighlightsCircRRAS2 expression is higher in DM cells than in GM cells.CircRRAS2 could significantly inhibit the proliferation and apoptosis of bovine MuSCs.CircRRAS2 promotes the differentiation of bovine MuSCs into myotubes.CircRRAS2 may exert regulatory effects through multiple RNA binding proteins.

Treatment of intracranial bifurcation aneurysms with "X" stent-assisted coiling: A case series and literature review.

PURPOSE: To clarify the safety and efficacy of "X" stent-assisted coiling (X-stenting) for the treatment of intracranial bifurcation aneurysms and to review the literature. METHODS: We retrospectively reported five consecutive patients with six intracranial bifurcation aneurysms who underwent X-stenting between June 2014 and June 2020. The clinical and angiographic results were analyzed. We also performed an extensive PubMed review of medical literature up to June 2021. RESULTS: Endovascular procedures were successfully applied to all six aneurysms. No procedure-related complications were noted. Follow-up angiograms were available for all patients and revealed occlusion in five aneurysms and improvement in one aneurysm. Clinical follow-up was performed for all patients, and the mRS score at follow-up was 0 in all patients. Thus, good outcomes were achieved in all patients, and no ischemic or hemorrhagic events were observed. CONCLUSIONS: X-stenting appears to be safe for treating intracranial bifurcation aneurysms and effective in immediate and short-term outcome. Further research is required with well-designed, prospective studies with large sample sizes.

Effect of Occlusion Site on the Safety and Efficacy of Intravenous Alteplase Before Endovascular Thrombectomy: A Prespecified Subgroup Analysis of DIRECT-MT.

BACKGROUND AND PURPOSE: Recent trials showed thrombectomy alone was comparable to bridging therapy in patients with anterior circulation large vessel occlusion eligible for both intravenous alteplase and endovascular thrombectomy. We performed this study to examine whether occlusion site modifies the effect of intravenous alteplase before thrombectomy. METHODS: This is a prespecified subgroup analysis of a randomized trial evaluating risk and benefit of intravenous alteplase before thrombectomy (DIRECT-MT [Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals]). Among 658 randomized patients, 640 with baseline occlusion site information were included. The primary outcome was the score on the modified Rankin Scale at 90 days. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by occlusion location (internal carotid artery versus M1 versus M2). We report the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after thrombectomy alone compared with combination treatment adjusted for age, the National Institutes of Health Stroke Scale score at baseline, the time from stroke onset to randomization, the modified Rankin Scale score before stroke onset, and collateral score per the DIRECT-MT statistical analysis plan. RESULTS: The overall adjusted common odds ratio was 1.08 (95% CI, 0.82-1.43) with thrombectomy alone compared with combination treatment, and there was no significant treatment-by-occlusion site interaction (P=0.47). In subgroups based on occlusion location, we found the following adjusted common odds ratios: 0.99 (95% CI, 0.62-1.59) for internal carotid artery occlusions, 1.12 (95% CI, 0.77-1.64) for M1 occlusions, and 1.22 (95% CI, 0.53-2.79) for M2 occlusions. No treatment-by-occlusion site interactions were observed for dichotomized modified Rankin Scale distributions and successful reperfusion (extended thrombolysis in Cerebral Infarction score ≥2b) before thrombectomy. Differences in symptomatic hemorrhage rate were not significant between occlusion locations (internal carotid artery occlusion: 7.02% in bridging therapy versus 7.14% for thrombectomy alone, P=0.97; M1 occlusion: 5.06% versus 2.48%, P=0.22; M2 occlusion: 9.09% versus 4.76%; P=0.78). CONCLUSIONS: In this prespecified subgroup of a randomized trial, we found no evidence that occlusion location can inform intravenous alteplase decisions in endovascular treatment eligible patients directly presenting at endovascular treatment capable centers. Future studies are needed to confirm our findings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03469206.

CircUBE2Q2 promotes differentiation of cattle muscle stem cells and is a potential regulatory molecule of skeletal muscle development.

BACKGROUND: The growth and development of muscle stem cells (MuSCs) are significant events known to affect muscle plasticity, disease, meat production, and meat quality, which involves the types and functions of mRNA and non-coding RNA. Here, MuSCs were cultured from Guangxi fetal cattle. RNA sequencing was used to analyze the RNA expression of mRNA and non-coding RNAs during the cell proliferation and differentiation phases. RESULTS: Two thousand one hundred forty-eight mRNAs and 888 non-coding RNAs were differentially expressed between cell proliferation and differentiation phases, including 113 miRNAs, 662 lncRNAs, and 113 circRNAs. RT-qPCR verified the differential expression levels of mRNAs and non-coding RNAs, and the differentially expressed circUBE2Q2 was subsequently characterized. Expression profile analysis revealed that circUBE2Q2 was abundant in muscle tissues and intramuscular fat. The expression of cricUBE2Q2 was also significantly upregulated during MuSCs myogenic differentiation and SVFs adipogenic differentiation and decreased with age in cattle muscle tissue. Finally, the molecular mechanism of circUBE2Q2 regulating MuSCs function that affects skeletal muscle development was investigated. The results showed that circUBE2Q2 could serve as a sponge for miR-133a, significantly promoting differentiation and apoptosis of cultured MuSCs, and inhibiting proliferation of MuSCs. CONCLUSIONS: CircUBE2Q2 is associated with muscle growth and development and induces MuSCs myogenic differentiation through sponging miR-133a. This study will provide new clues for the mechanisms by which mRNAs and non-coding RNAs regulate skeletal muscle growth and development, affecting muscle quality and diseases.

Biuret Induced Tin-Anchoring and Crystallization-Regulating for Efficient Lead-Free Tin Halide Perovskite Light-Emitting Diodes.

Lead-free perovskite emitters, particularly 2D tin (Sn) halide perovskites, have attracted considerable academic attention in recent years. However, the problems of Sn oxidation and rapid crystallization lead to an inferior perovskite morphology with high trap states, thus limiting the luminous efficiency of Sn halide perovskite light-emitting diodes (PeLEDs). In this study, the authors establish an approach by introducing an organic additive, 2-imidodicarbonic diamide (biuret), to address the issues of Sn oxidation and fast crystallization. The unique symmetrical carbonyl groups in the biuret robustly interact with the Sn-I framework, providing a strong Sn-anchoring effect. Consequently, it also suppresses the easy oxidation of Sn2+ , regulating the crystallization process simultaneously. Density functional theory (DFT) calculations also confirmed the robust interaction between the biuret and the 2D Sn halide perovskite. Furthermore, the authors demonstrate efficient PeLEDs with saturated red emission at 637 nm, a maximum luminance (Lmax ) of 418 cd m-2 , a maximum external quantum efficiency (EQEmax ) of 1.37%, and a half-life (T50 ) of 288 s. This work provides insights on the microcosmic chemical interaction between organics and 2D Sn halide perovskites, advancing the development of efficient lead-free PeLEDs.

Detection of electrostatic molecular binding using the water proton signal.

PURPOSE: Saturation transfer MRI has previously been used to probe molecular binding interactions with signal enhancement via the water signal. Here, we detail the relayed nuclear overhauser effect (rNOE) based mechanisms of this signal enhancement, develop a strategy of quantifying molecular binding affinity, i.e., the dissociation constant ( KD$$ {K}_D $$ ), and apply the method to detect electrostatic binding of several charged small biomolecules. Another goal was to estimate the detection limit for transient receptor-substrate binding. THEORY AND METHODS: The signal enhancement mechanism was quantitatively described by a three-step magnetization transfer model, and numerical simulations were performed to verify this theory. The binding equilibria of arginine, choline, and acetyl-choline to anionic resin were studied as a function of ligand concentration, pH, and salt content. Equilibrium dissociation constants ( KD$$ {K}_D $$ ) were determined by fitting the multiple concentration data. RESULTS: The numerical simulations indicate that the signal enhancement is sufficient to detect the molecular binding of sub-millimolar (∼100 µM) concentration ligands to low micromolar levels of molecular targets. The measured rNOE signals from arginine, choline, and acetyl-choline binding experiments show that several magnetization transfer pathways (intra-ligand rNOEs and intermolecular rNOEs) can contribute. The rNOEs that arise from molecular ionic binding were influenced by pH and salt concentration. The molecular binding strengths in terms of KD$$ {K}_{\mathrm{D}} $$ ranged from 70-160 mM for the three cations studied. CONCLUSION: The capability to use MRI to detect the transient binding of small substrates paves a pathway towards the detection of micromolar level receptor-substrate binding in vivo.