Distinguishing high-metastasis-potential circulating tumor cells through fluidic shear stress in a bloodstream-like microfluidic circulatory system.

Circulating tumor cells (CTCs) play a critical role as initiators in tumor metastasis, which unlocks an irreversible process of cancer progression. Regarding the fluid environment of intravascular CTCs, a comprehensive understanding of the impact of hemodynamic shear stress on CTCs is of profound significance but remains vague. Here, we report a microfluidic circulatory system that can emulate the CTC microenvironment to research the responses of typical liver cancer cells to varying levels of fluid shear stress (FSS). We observe that HepG2 cells surviving FSS exhibit a marked overexpression of TLR4 and TPPP3, which are shown to be associated with the colony formation, migration, and anti-apoptosis abilities of HepG2. Furthermore, overexpression of these two genes in another liver cancer cell line with normally low TLR4 and TPPP3 expression, SK-Hep-1 cells, by lentivirus-mediated transfection also confirms the critical role of TLR4 and TPPP3 in improving colony formation, migration, and survival capability under a fluid environment. Interestingly, in vivo experiments show SK-Hep-1 cells, overexpressed with these genes, have enhanced metastatic potential to the liver and lungs in mouse models via tail vein injection. Mechanistically, TLR4 and TPPP3 upregulated by FSS may increase FSS-mediated cell survival and metastasis through the p53-Bax signaling pathway. Moreover, elevated levels of these genes correlate with poorer overall survival in liver cancer patients, suggesting that our findings could offer new therapeutic strategies for early cancer diagnosis and targeted treatment development.

Active Constituents with Tyrosinase Inhibitory Activities from Waste Tobacco Leaves.

One novel compound, (R)-3, 6-diethoxy-4-hydroxycyclohex-3-en-1-one (1) and thirteen known compounds were isolated from the waste tobacco leaves. The structures of two compounds (1-2) were confirmed and attributed firstly by the extensive spectroscopic data, including 1D/2D NMR, IR, HR-ESI-MS, CD, and ECD spectra. Notably, seven compounds (2, 3, 9, 10, 11, 12, and 13) exhibited better tyrosinase inhibitory activity than the positive control kojic acid. The binding modes of these compounds revealed that their structure formed strong hydrogen bonds and van der Waals forces with the active sites of tyrosinase. These results indicated that waste tobacco leaves are good resources for developing tyrosinase inhibitors.

A High-Throughput Microdroplet-Based Single Cell Transfection Method for Gene Knockout Based on the CRISPR/Cas9 System.

The efficient application of the newly developed gene-editing method CRISPR/Cas9 requires more accurate intracellular gene delivery. Traditional delivery approaches, such as lipotransfection and non-viral delivery methods, must contend with major problems to overcome the drawbacks of low efficiency, high toxicity, and cell-type dependency. The high-throughput microdroplet-based single-cell transfection method presented herein provides an alternative method for delivering genome-editing reagents into single living cells. By accurately controlling the number of exogenous plasmids in microdroplets, this method can achieve high-efficiency delivery of nucleic acids to different types of single cells. This paper presents a high-throughput quantitative DNA transfection method for single cells and explores the optimal DNA transfection conditions for specific cell lines. The transfection efficiency of cells at different concentrations of DNA in microdroplets is measured. Under the optimized transfection conditions, the method is used to construct gene-knockout cancer cell lines to determine specific gene functions through the CRISPR/Cas9 knockout system. In a case study, the migration ability of TRIM72 knockout cancer cells is inhibited, and the tumorigenicity of cells in a zebrafish tumor model is reduced. A single-cell microfluidic chip is designed to achieve CRISPR/Cas9 DNA transfection, dramatically improving the transfection efficiency of difficult-to-transfect cells. This research demonstrates that the microdroplet method developed herein has a unique advantage in CRISPR/Cas9 gene-editing applications.

The diagnostic value of sST2 for myocardial fibrosis in idiopathic inflammatory myopathies in subclinical stage of cardiac involvement.

OBJECTIVE: Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. METHODS: A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. RESULTS: IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s.d. 30.4)] vs 14.4 (5.5), P < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P = 0.000), ECV (r = 0.371, P = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P < 0.01), respectively. CONCLUSION: sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM.

An integrated and multi-functional droplet-based microfluidic platform for digital DNA amplification.

Digital DNA amplification is a powerful method for detecting and quantifying rare nucleic acids. In this study, we developed a multi-functional droplet-based platform that integrates the traditional digital DNA amplification workflow into a one-step device. This platform enables efficient droplet generation, transition, and signal detection within a 5-min timeframe, distributing the sample into a uniform array of 4 × 104 droplets (variation <2%) within a chamber. Subsequent in-situ DNA amplification, fluorescence detection, and signal analysis were carried out. To assess the platform's performance, we quantitatively detected the human epidermal growth factor receptor (EGFR) mutation and human papillomavirus (HPV) mutation using digital polymerase chain reaction (dPCR) and digital loop-mediated isothermal amplification (dLAMP), respectively. The fluorescence results exhibited a positive, linear, and statistically significant correlation with target DNA concentrations ranging from 101 to 105 copies/µL, demonstrating the capability and feasibility of the integrated device for dPCR and dLAMP. This platform offers high-throughput droplet generation, eliminates droplet fusion and transition, is user-friendly, reduces costs compared to current methods, and holds potential for thermocycling and isothermal nucleic acid quantification with high sensitivity and accuracy.

Pyroptosis-related gene signature: A predictor for overall survival, immunotherapy response, and chemosensitivity in patients with pancreatic adenocarcinoma.

Background: Pancreatic adenocarcinoma (PAAD) is a lethal malignancy with high levels of heterogeneity. Pyroptosis is thought to influence the development of various tumors. Nevertheless, the role of pyroptosis-related genes (PRGs) in prognostic risk stratification and therapeutic guidance for PAAD remains ambiguously. Methods: Transcriptome profile and clinical information of PAAD patients were retrieved from The Cancer Genome Atlas (TCGA) as well as Gene Expression Omnibus (GEO) databases, followed by differential analysis. Patients were divided into distinct pyroptosis phenotype subtypes based on the characteristic of differently expressed PRGs (DEPRGs). Then a PRG signature was established through univariate analysis and LASSO algorithm in the training set to assess the prognostic risk, and its reliability was verified in the validation set using receiver operating characteristic(ROC) curve. The correlation of risk score with tumor microenvironment(TME), TMB and chemotherapeutic drug sensitivity were also analyzed. In addition, a nomogram was constructed to promote better clinical application. Results: A total of 28 DEPRGs were determined in the integrated TCGA-GEO datasets. Patients were divided into three pyroptosis phenotype subtypes, Kaplan-Meier curve suggested patients in cluster B had a worse prognosis than those in cluster A and C. Then a price signature comprised of 8 PRGs was generated. TME analysis suggested that the low-risk subgroup displayed potential stronger antitumor immune effect and might respond better to immune checkpoint inhibitors (ICIs) therapy. Furthermore, PRG signature exhibited favorable discriminatory ability for TMB status and the sensitivity of multiple conventional chemotherapeutic agents including paclitaxel. Ultimately, we constructed a promising nomogram according to the risk score and N stage with good predictive accuracy compared with the actual overall survival (OS) probabilities. Conclusion: We established an 8-gene signature that could be regarded as an independent prognostic risk factor for PAAD patients. The 8-gene signature could provide rationale for immunotherapy and chemotherapy, which might help clinicians make precise individualized treatment regimens.

Pulmonary Transit Time Derived from First-Pass Perfusion Cardiac MR Imaging: A Potential New Marker for Cardiac Involvement and Prognosis in Light-Chain Amyloidosis.

BACKGROUND: First-pass perfusion cardiac MR imaging could reflect pulmonary hemodynamics. However, the clinical value of pulmonary transit time (PTT) derived from first-pass perfusion MRI in light-chain (AL) amyloidosis requires further evaluation. PURPOSE: To assess the clinical and prognostic value of PTT in patients with AL amyloidosis. STUDY TYPE: Prospective observational study. POPULATION: 226 biopsy-proven systemic AL amyloidosis patients (age 58.62 ± 10.10 years, 135 males) and 43 healthy controls (age 42 ± 16.2 years, 20 males). FIELD STRENGTH/SEQUENCE: SSFP cine and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences, and multislice first-pass myocardial perfusion imaging with a saturation recovery turbo fast low-angle shot (SR-TurboFLASH) pulse sequence at 3.0T. ASSESSMENT: PTT was measured as the time interval between the peaks of right and left ventricular cavity arterial input function curves on first-pass perfusion MR images. STATISTICAL TESTS: Independent-sample t test, Mann-Whitney U test, Chi-square test, Fisher's exact test, analysis of variance, or Kruskal-Wallis test, as appropriate; univariable and multivariable Cox proportional hazards models and Kaplan-Meier curves, area under receiver operating characteristic curve were used to determine statistical significance. RESULTS: PTT could differentiate AL amyloidosis patients with (N = 188) and without (N = 38) cardiac involvement (area under the curve [AUC] = 0.839). During a median follow-up of 35 months, 160 patients (70.8%) demonstrated all-cause mortality. After adjustments for clinical (Hazard ratio [HR] 1.061, confidence interval [CI]: 1.021-1.102), biochemical (HR 1.055, CI: 1.014-1.097), cardiac MRI-derived (HR 1.077, CI: 1.034-1.123), and therapeutic (HR 1.063, CI: 1.024-1.103) factors, PTT predicted mortality independently in patients with AL amyloidosis. Finally, PTT could identify worse outcomes in patients demonstrating New York Heart Association class III, Mayo 2004 stage III, and transmural LGE pattern. DATA CONCLUSION: PTT may serve as a new imaging predictor of cardiac involvement and prognosis in AL amyloidosis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

[Clinical analysis of distal radius core decompression for chronic wrist pain].

Objective: To investigate the effectiveness of distal radius core decompression in the treatment of chronic wrist pain caused by various etiologies. Methods: A retrospective analysis was performed for the clinical data of 10 patients with chronic wrist pain treated with distal radial core decompression between January 2018 and December 2021. There were 6 males and 4 females with an average age of 37.4 years (range, 21-55 years). The disease duration ranged from 7 to 72 months, with an average of 26.5 months. Preoperative MRI examination showed that 10 cases had bone marrow edema at the distal radius on the affected side, and 8 cases had bone marrow edema in the carpal bones such as scaphoid and lunate bone. Among them, 3 patients had a history of wrist fracture, and 2 patients had Kienböck diseases (1 case each in stage ⅡB and stage ⅢA). Three cases were combined with triangular fibrocartilage complex (TFCC) type 1A injury. Two cases were combined with osteoarthritis, 1 of them was complicated with severe traumatic arthritis, the wrist arthroscopy showed that the TFCC was completely lost and could not be repaired, and the cartilage of the lunate bone and the ulnar head were severely worn.Visual analogue scale (VAS) score was used to evaluate the relief of wrist pain before operation, at 6 months after operation, and at last follow-up, and the range of motion of the affected wrist in dorsiflexion, palmar flexion, ulnar deviation, and radial deviation was measured. The degree of bone marrow edema was evaluated according to T1WI, T2WI, and STIR sequences of MRI. Results: All the patients were followed up 12-22 months, with an average of 16.4 months. Except for 1 patient who experienced persistent wrist joint pain and limited mobility after operation, the remaining 9 patients showed significant improvement in pain symptoms and wrist joint mobility. The VAS score and range of motion of wrist dorsiflexion, palmar flexion, ulnar deviation, and radial deviation at 6 months after operation and at last follow-up were significantly improved when compared with those before operation, the VAS score and the range of motion of wrist ulnar deviation and radial deviation at last follow-up were further improved when compared with those at 6 months after operation, all showing significant differences ( P<0.05). There was no significant difference in wrist dorsiflexion and palmar flexion between at 6 months after operation and at last follow-up ( P>0.05). Bone marrow edema was improved in 6 patients on MRI at 6 months after operation, and was also improved in other patients at last follow-up. Conclusion: For chronic wrist pain caused by a variety of causes, distal radius core decompression can directly reduce the pressure of the medullary cavity of the distal radius, improve the blood supply of the corresponding distal structure, significantly alleviate chronic wrist pain, and provide an option for clinical treatment.

Significance of ypTNM stage in determining the prognosis and therapy after surgery for locally advanced rectal cancer.

BACKGROUND: In the current NCCN guidelines, the prognosis and adjuvant chemotherapy of patients who underwent neoadjuvant chemoradiotherapy (nCRT) are based on pre-radiotherapy clinical TNM (cTNM) stage. However, the value of neoadjuvant pathologic TNM (ypTNM) stage is not clearly described. METHODS: This retrospective study investigated the prognosis and adjuvant chemotherapy which based on ypTNM stage compared to cTNM stage. Between 2010 and 2015, a total of 316 rectal cancer patients who underwent nCRT, followed by total mesorectal excision (TME), were included for analysis. RESULTS: Our findings revealed that cTNM stage was the only significant independent factor in the pCR group (HR = 6.917, 95% CI: 1.133-42.216, P = 0.038). In the non-pCR group, ypTNM stage was more important than cTNM stage in prognosis (HR = 2.704, 95% CI: 1.811-4.038, P < 0.001). In ypTNM III stage group, there was a statistically significant difference in prognosis between the patients with and without adjuvant chemotherapy (HR = 1.943, 95% CI: 1.015-3.722, P = 0.040), but there was no significant difference in cTNM III stage group (HR = 1.430, 95% CI: 0.728-2.806, P = 0.294). CONCLUSIONS: We concluded that ypTNM stage, rather than cTNM stage, might be a more important factor in the prognosis and adjuvant chemotherapy of patients with rectal cancer who underwent nCRT.

SPatiotemporal-ENcoded acoustic radiation force imaging of focused ultrasound.

Neuromodulation technology has provided novel therapeutic approaches for diseases caused by neural circuit dysfunction. Transcranial focused ultrasound (FU) is an emerging neuromodulation approach that combines noninvasiveness with relatively sharp focus, even in deep brain regions. It has numerous advantages such as high precision and good safety in neuromodulation, allowing for modulation of both peripheral and central nervous systems. To ensure accurate treatment targeting in FU neuromodulation, a magnetic resonance acoustic radiation force imaging (MR-ARFI) sequence is crucial for the visualization of the focal point. Currently, the commonly used 2D Spin Echo ARFI (2D SE-ARFI) sequence suffers from the long acquisition time, while the echo planar imaging ARFI (EPI-ARFI) sequence with a shorter acquisition time is vulnerable to the magnetic field inhomogeneities. To address these problems, we proposed a spatiotemporal-encoded acoustic radiation force imaging sequence (i.e., SE-SPEN-ARFI, shortened to SPEN-ARFI) in this study. The displacement at the focal spot obtained was highly consistent with that of the SE-ARFI sequence. Our research shows that SPEN-ARFI allows for rapid image acquisition and has less image distortions even under great field inhomogeneities. Therefore, a SPEN-ARFI sequence is a practical alternative for the treatment planning in ultrasound neuromodulation.

Metabolic Glycan Labeling in Primary Neurons Enabled by Unnatural Sugars with No S-Glyco-Modification.

It is of great interest to probe glycosylation in primary neuron cultures. However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. Here, we uncovered that neuron cytotoxicity of per-O-acetylated unnatural sugars was related to their reactions with protein cysteines via non-enzymatic S-glyco-modification. The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. Particularly, a total of 505 sialylated N-glycosylation sites distributed on 345 glycoproteins were identified by 1,6-Pr2ManNAz.

Cellular-scale proximity labeling for recording cell spatial organization in mouse tissues.

Proximity labeling has emerged as a powerful strategy for interrogating cell-cell interactions. However, the nanometer-scale labeling radius impedes the use of current methods for indirect cell communications and makes recording cell spatial organization in tissue samples difficult. Here, we develop quinone methide-assisted identification of cell spatial organization (QMID), a chemical strategy with the labeling radius matching the cell dimension. The activating enzyme is installed on the surface of bait cells, which produces QM electrophiles that can diffuse across micrometers and label proximal prey cells independent of cell-cell contacts. In cell coculture, QMID reveals gene expression of macrophages that are regulated by spatial proximity to tumor cells. Furthermore, QMID enables labeling and isolation of proximal cells of CD4+ and CD8+ T cells in the mouse spleen, and subsequent single-cell RNA sequencing uncovers distinctive cell populations and gene expression patterns within the immune niches of specific T cell subtypes. QMID should facilitate dissecting cell spatial organization in various tissues.

Multi-channel deep learning model-based myocardial spatial-temporal morphology feature on cardiac MRI cine images diagnoses the cause of LVH.

BACKGROUND: To develop a fully automatic framework for the diagnosis of cause for left ventricular hypertrophy (LVH) via cardiac cine images. METHODS: A total of 302 LVH patients with cine MRI images were recruited as the primary cohort. Another 53 LVH patients prospectively collected or from multi-centers were used as the external test dataset. Different models based on the cardiac regions (Model 1), segmented ventricle (Model 2) and ventricle mask (Model 3) were constructed. The diagnostic performance was accessed by the confusion matrix with respect to overall accuracy. The capability of the predictive models for binary classification of cardiac amyloidosis (CA), hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) were also evaluated. Additionally, the diagnostic performance of best Model was compared with that of 7 radiologists/cardiologists. RESULTS: Model 3 showed the best performance with an overall classification accuracy up to 77.4% in the external test datasets. On the subtasks for identifying CA, HCM or HHD only, Model 3 also achieved the best performance with AUCs yielding 0.895-0.980, 0.879-0.984 and 0.848-0.983 in the validation, internal test and external test datasets, respectively. The deep learning model showed non-inferior diagnostic capability to the cardiovascular imaging expert and outperformed other radiologists/cardiologists. CONCLUSION: The combined model based on the mask of left ventricular segmented from multi-sequences cine MR images shows favorable and robust performance in diagnosing the cause of left ventricular hypertrophy, which could be served as a noninvasive tool and help clinical decision.

Comparison between pre- and post-contrast cardiac MRI cine images: the impact on ventricular volume and strain measurement.

To explore whether contrast agent administration will affect ventricular volume and strain parameters measured on cardiac magnetic resonance cine images. This prospective study enrolled 88 patients, including 32 patients with cardiac amyloidosis (CA), 32 patients with hypertrophic cardiomyopathy (HCM), and 24 control participants, to perform steady-state free precession (SSFP)-cine imaging twice, respectively before and after contrast agent injection. Indexed left and right ventricular (LV and RV) volume and LV strain parameters (peak radial strain [PRS], peak circumferential strain [PCS], peak longitudinal strain [PLS]) were analyzed and compared between the pre- and post-contrast cine groups. Compared to the group of pre-contrast cine, the end-diastolic volume index (EDVi) and end-systolic volume index (ESVi) significantly increased in the group using post-contrast cine images (all p < 0.05), especially in the right ventricle. After contrast injection, the right ventricular ejection fraction (RVEF) decreased significantly (p < 0.05), while the left ventricular ejection fraction (LVEF) only reduced for patients with HCM (p < 0.05). The PRS (37.1 ± 15.2 vs. 32.0 ± 15.4, p < 0.001) and PCS (- 14.9 ± 4.3 vs. - 14.0 ± 4.1, p < 0.001) derived from post-contrast cine images reduced significantly in all patients and this tendency remained in subgroup analysis except for PCS in the control group. The administration of a contrast agent may influence the measurements of ventricular volume and strain. Acquiring pre-contrast cine images were suggested for patients who required more accurate right ventricle evaluation or precise strain assessment.

Changing handedness after nerve reconstruction in brachial plexus birth palsy.

Purpose: Right obstetric brachial plexus injuries (OBPI) often lead to left-handedness before limb function is restored post-surgery. A pertinent question arises about promoting a transition from left to right-handedness. We hypothesized that, with the decrease in neuroplasticity, handedness switching is not only difficult, but also reduces handedness-speech lateralization, impaired motor adaptability, and compromised language proficiency. Methods: We retrospectively analyzed clinical data from January 1996 to January 2012 at our hospital. Participants were divided into intervention or control groups based on handedness switching. We compared handedness and computed lateral quotient (LQ) and lateralization index (LI) for handedness-speech center. Additionally, we assessed dominant hand's writing speed, language function, and IQ. Associations between absolute LI and LQ values, writing speed, language scores, and IQ were examined. Results: Nineteen extended Erb's palsy participants were enrolled, eight in the intervention group, and 11 in the control. No right-handed individuals were found in either cohort. The intervention group had significantly lower LQ and LI values, and fewer achieved normal writing speed. Yet, no notable disparities in language scores or IQ emerged. Notably, we established correlations between motor finesse, handedness degree, and handedness-speech lateralization. Conclusion: For right extended Erb's palsy, shifting handedness is nearly unfeasible, and such an endeavor could trigger a reduction in handedness-speech lateralization magnitude and diminished motor finesse.

Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy and in vitro.

In obstetric brachial plexus palsy (OBPP), the operative time window for nerve reconstruction of the intrinsic muscles of the hand (IMH) is much shorter than that of biceps. The reason is that the atrophy of IMH becomes irreversible more quickly than that of biceps. A previous study confirmed that the motor endplates of denervated intrinsic muscles of the forepaw (IMF) were destabilized, while those of denervated biceps remained intact. However, the specific molecular mechanism of regulating the self-repair of motor endplates is still unknown. In this study, we use a rat model of OBPP with right C5-C6 rupture plus C7-C8-T1 avulsion and left side as a control. Bilateral IMF and biceps are harvested at 5 weeks postinjury to assess relative protein and mRNA expression. We also use L6 skeletal myoblasts to verify the effects of signaling pathways regulating acetylcholine receptor (AChR) protein synthesis in vitro. The results show that in the OBPP rat model, the protein and mRNA expression levels of NRG-1/ErbB4 and phosphorylation of Akt/mTOR/p70S6K are lower in denervated IMF than in denervated biceps. In L6 myoblasts stimulated with NRG-1, overexpression and knockdown of ErbB4 lead to upregulation and downregulation of AChR subunit protein synthesis and Akt/mTOR/p70S6K phosphorylation, respectively. Inhibition of mTOR abolishes protein synthesis of AChR subunits elevated by NRG-1/ErbB4. Our findings suggest that in the OBPP rat model, lower expression of AChR subunits in the motor endplates of denervated IMF is associated with downregulation of NRG-1/ErbB4 and phosphorylation of Akt/mTOR/p70S6K. NRG-1/ErbB4 can promote protein synthesis of the AChR subunits in L6 myoblasts via phosphorylation of Akt/mTOR/p70S6K.

Preoperative Computed Tomography Radiomics Analysis for Predicting Receptors Status and Ki-67 Levels in Breast Cancer.

BACKGROUND: To assess the prediction performance of preoperative chest computed tomography (CT) based radiomics features for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2+), and Ki-67 status of breast cancer. MATERIALS AND METHODS: This study enrolled 108 breast cancer patients who received preoperative chest CT examinations in our institution from July 2018 to January 2020. Radiomics features were separately extracted from nonenhanced, arterial, and portal-venous phases CT images. The least absolute shrinkage and selection operator logistic regression was used for feature selection. Then the radiomics signatures for each phase and a combined model of 3 phases were built. Finally, the receiver operating characteristic curves and calibration curves were used to confirm the performance of the radiomics signatures and combined model. In addition, the decision curves were performed to estimate the clinical usefulness of the combined model. RESULTS: The 20 most predictive features were finally selected to build radiomics signatures for each phase. The combined model achieved the overall best performance than using either of the nonenhanced, arterial and portal-venous phases alone, achieving an area under the receiver operating characteristic curve of 0.870 for ER+ versus ER-, 0.797 for PR+ versus PR-, 0.881 for HER2+ versus HER2-, and 0.726 for Ki-67. The decision curve demonstrated that the CT-based radiomics features were clinically useful. CONCLUSION: This study indicated preopreative chest CT radiomics analysis might be able to assess ER, PR, HER2+, and Ki-67 status of breast cancer. The findings need further to be verified in future larger studies.

Brain structural network to investigate the mechanism of cognitive impairment in patients with acoustic neuroma.

Objective: Acoustic neuroma (AN) is a common benign tumor. Little is known of neuropsychological studies in patients with acoustic neuroma, especially cognitive neuropsychology, and the neuropsychological abnormalities of patients affect their life quality. The purpose of this study was to explore the changes in the cognitive function of patients with acoustic neuroma, and the possible mechanism of these changes by structural magnetic resonance imaging. Materials and methods: We used a neuropsychological assessment battery to assess cognitive function in 69 patients with acoustic neuroma and 70 healthy controls. Then, we used diffusion tensor imaging data to construct the structural brain network and calculate topological properties based on graph theory, and we studied the relation between the structural brain network and cognitive function. Moreover, three different subnetworks (short-range subnetwork, middle-range subnetwork, and long-range subnetwork) were constructed by the length of nerve fibers obtained from deterministic tracking. We studied the global and local efficiency of various subnetworks and analyzed the correlation between network metrics and cognitive function. Furthermore, connectome edge analysis directly assessed whether there were differences in the number of fibers in the different brain regions. We analyzed the relation between the differences and cognitive function. Results: Compared with the healthy controls, the general cognitive function, memory, executive function, attention, visual space executive ability, visual perception ability, movement speed, and information processing speed decreased significantly in patients with acoustic neuroma. A unilateral hearing loss due to a left acoustic neuroma had a greater impact on cognitive function. The results showed that changes in the global and local metrics, the efficiency of subnetworks, and cognitively-related fiber connections were associated with cognitive impairments in patients with acoustic neuroma. Conclusion: Patients exhibit cognitive impairments caused by the decline of the structure and function in some brain regions, and they also develop partial compensation after cognitive decline. Cognitive problems are frequent in patients with acoustic neuroma. Including neuropsychological aspects in the routine clinical evaluation and appropriate treatments may enhance the clinical management and improve their life quality.

Accelerated 3D high-resolution T2-weighted breast MRI with deep learning constrained compressed sensing, comparison with conventional T2-weighted sequence on 3.0 T.

PURPOSE: To evaluate the feasibility of isotropic 3D high-resolution T2-weighted imaging (T2WI) MRI sequences and compare the images reconstructed by integrating artificial intelligence-compressed sensing (AI-CS), compressed sensing (CS), and conventional 2D T2WI sequences for quality. MATERIALS AND METHODS: Fifty-two female patients (ages: 26-80 years) with suspected breast cancer were enrolled. They underwent breast MRI examinations using three sequences: conventional T2WI, CS 3D T2WI, and AI-CS 3D T2WI. Image quality, signal-to-noise ratio (SNR), contrast-to-noise ratio, tumor volume, and maximal tumor diameter were compared using the Friedman test. Image quality was scored on a 5-point scale, with 1 indicating nonassessable quality and 5 indicating excellent quality. Tumor volume and maximal tumor diameter were compared based on AI-CS 3D T2WI (slightly high signal), conventional T2WI, and dynamic contrast-enhanced (DCE) sequences. RESULTS: All three T2WI were successfully performed in all patients. 3D CS and AI-CS were significantly better than conventional T2WI in terms of lesion conspicuity and morphology, structural details, overall image quality, diagnostic information for breast lesions, and breast tissue delineation (P < 0.001). The SNR of conventional T2WI was significantly higher for 3D T2WI sequences. The contrast-to-noise ratio was significantly higher for AI-CS 3D T2WI than for conventional T2WI sequence. There was no significant difference in tumor volume between DCE (8.08 ± 16.51) and AI-CS 3D T2WI (8.25 ± 16.29) sequences and no significant differences in tumor diameter among DCE, AI-CS 3D T2WI, and conventional T2WI sequences. CONCLUSION: Isotropic-resolution 3D T2WI sequences can be acquired using AI-CS while maintaining image quality and diagnostic value, which may pave the way for isotropic 3D high-resolution T2WI for clinical application.

DNA2 mutation causing multisystemic disorder with impaired mitochondrial DNA maintenance.

PURPOSE: To describe a novel DNA2 variant contributing to defects in mtDNA maintenance and mtDNA depletion syndrome (MDS), and the clinical and histological findings associated with this variation. METHODS: Herein, we describe the case of a patient who presented with hearing loss and myopathy, given the family history of similar findings in the father, was evaluated by sequencing of the deafness gene panel, mitochondrial genome, and the exome. Furthermore, tissue staining, mtDNA copy number detection, mtDNA sequencing, and long-range polymerase chain reaction tests were also conducted on the muscle biopsy specimen. In vitro experiments, including analyses of the mtDNA copy number; levels of ATP, ATPase, and reactive oxygen species (ROS); and the membrane potential, were performed. RESULTS: The DNA2 heterozygous truncating variant c. 2368C > T (p.Q790X) was identified and verified as the cause of an mtDNA copy number decrement in both functional experiments and muscle tissue analyses. These changes were accompanied by reductions in ATP, ATPase, and ROS levels. CONCLUSION: The DNA2 variant was a likely cause of MDS in this patient. These findings expand the mutational spectrum of MDS and improve our understanding of the functions of DNA2 by revealing its novel role in mtDNA maintenance.