Imaging and quantification of human and viral circular RNAs.

We present a robust approach for cellular detection, imaging, localization, and quantification of human and viral encoded circular RNAs (circRNA) using amplified fluorescence in situ hybridization (ampFISH). In this procedure, a pair of hairpin probes bind next to each other at contiguous stretches of sequence and then undergo a conformational reorganization which initiates a target-dependent hybridization chain reaction (HCR) resulting in deposition of an amplified fluorescent signal at the site. By harnessing the capabilities of both ampFISH and single-molecule FISH (smFISH), we selectively identified and imaged circular RNAs and their linear counterparts derived from the human genome, SARS-CoV-2 (an RNA virus), and human cytomegalovirus (HCMV, a DNA virus). Computational image processing facilitated accurate quantification of circular RNA molecules in individual cells. The specificity of ampFISH for circular RNA detection was confirmed through an in situ RNase R treatment that selectively degrades linear RNAs without impacting circular RNAs. The effectiveness of circular RNA detection was further validated by using ampFISH probes with mismatches and probe pairs that do not bind to the continuous sequence in their target RNAs but instead bind at segregated sites. An additional specificity test involved probes against the negative strands of the circular RNA sequence, absent in the cell. Importantly, our technique allows simultaneous detection of circular RNAs and their linear counterparts within the same cell with single molecule sensitivity, enabling explorations of circular RNA biogenesis, subcellular localization, and functions.

New intranasal and injectable gene therapy for healthy life extension.

As the global elderly population grows, it is socioeconomically and medically critical to provide diverse and effective means of mitigating the impact of aging on human health. Previous studies showed that the adeno-associated virus (AAV) vector induced overexpression of certain proteins, which can suppress or reverse the effects of aging in animal models. In our study, we sought to determine whether the high-capacity cytomegalovirus vector (CMV) can be an effective and safe gene delivery method for two such protective factors: telomerase reverse transcriptase (TERT) and follistatin (FST). We found that the mouse cytomegalovirus (MCMV) carrying exogenous TERT or FST (MCMVTERT or MCMVFST) extended median lifespan by 41.4% and 32.5%, respectively. We report CMV being used successfully as both an intranasal and injectable gene therapy system to extend longevity. Specifically, this treatment significantly improved glucose tolerance, physical performance, as well as preventing body mass loss and alopecia. Further, telomere shortening associated with aging was ameliorated by TERT and mitochondrial structure deterioration was halted in both treatments. Intranasal and injectable preparations performed equally well in safely and efficiently delivering gene therapy to multiple organs, with long-lasting benefits and without carcinogenicity or unwanted side effects. Translating this research to humans could have significant benefits associated with quality of life and an increased health span.

Transcriptomic analysis of differentially alternative splicing patterns in mice with inflammatory and neuropathic pain.

Although the molecular mechanisms of chronic pain have been extensively studied, a global picture of alternatively spliced genes and events in the peripheral and central nervous systems of chronic pain is poorly understood. The current study analyzed the changing pattern of alternative splicing (AS) in mouse brain, dorsal root ganglion, and spinal cord tissue under inflammatory and neuropathic pain. In total, we identified 6495 differentially alternatively spliced (DAS) genes. The molecular functions of shared DAS genes between these two models are mainly enriched in calcium signaling pathways, synapse organization, axon regeneration, and neurodegeneration disease. Additionally, we identified 509 DAS in differentially expressed genes (DEGs) shared by these two models, accounting for a small proportion of total DEGs. Our findings supported the hypothesis that the AS has an independent regulation pattern different from transcriptional regulation. Taken together, these findings indicate that AS is one of the important molecular mechanisms of chronic pain in mammals. This study presents a global description of AS profile changes in the full path of neuropathic and inflammatory pain models, providing new insights into the underlying mechanisms of chronic pain and guiding genomic clinical diagnosis methods and rational medication.

A recombination-resistant genome for live attenuated and stable PEDV vaccines by engineering the transcriptional regulatory sequences.

IMPORTANCE: Coronaviruses are important pathogens of humans and animals, and vaccine developments against them are imperative. Due to the ability to induce broad and prolonged protective immunity and the convenient administration routes, live attenuated vaccines (LAVs) are promising arms for controlling the deadly coronavirus infections. However, potential recombination events between vaccine and field strains raise a safety concern for LAVs. The porcine epidemic diarrhea virus (PEDV) remodeled TRS (RMT) mutant generated in this study replicated efficiently in both cell culture and in pigs and retained protective immunogenicity against PEDV challenge in pigs. Furthermore, the RMT PEDV was resistant to recombination and genetically stable. Therefore, RMT PEDV can be further optimized as a backbone for the development of safe LAVs.

Mechanisms of adverse mammary effect induced by olanzapine and therapeutic interventions in rat model.

BACKGROUND: Olanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. METHODS: Rats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5-40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. RESULTS: In adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. CONCLUSIONS: These results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.

Myocardial fibrosis and prognosis in heart failure with preserved ejection fraction: a pooled analysis of 12 cohort studies.

OBJECTIVES: Heart failure with preserved ejection fraction (HFpEF) is a syndrome with significant clinical heterogeneity. Myocardial fibrosis has been considered a common pathological process in the development and progress of HFpEF. This study aimed to consolidate data on the prognostic effect of myocardial fibrosis, evaluated by cardiovascular magnetic resonance (CMR) imaging in patients with HFpEF. METHODS: Three medical databases were searched for potentially related articles up to February 28, 2023. Cohort studies reporting associations between myocardial fibrosis and risk of all-cause mortality or composite major adverse cardiac outcomes (MACE) were included. Cardiac fibrosis was evaluated by CMR metrics, including late gadolinium enhancement (LGE) or myocardial extracellular volume (ECV). The hazard ratios (HRs) and 95% confidence intervals (CI) of the outcomes for higher myocardial fibrosis were calculated. RESULTS: Twelve studies with 2787 patients with HFpEF were included for analysis. After a median follow-up duration of 31.2 months, a higher level of cardiac fibrosis was associated with a significant increase in the risk of MACE (HR = 1.34, 95% CI = 1.14-1.57) and all-cause mortality (HR = 1.74, 95% CI = 1.27-2.39), respectively. Furthermore, the increased risk of outcomes was both observed when cardiac fibrosis was defined according to LGE or ECV, respectively. CONCLUSIONS: Higher burden of myocardial fibrosis evaluated by CMR can predict a poor prognosis in patients with HFpEF. Evaluation of LGE or ECV based on CMR could be recommended in these patients for risk stratification and guiding further treatment. CLINICAL RELEVANCE STATEMENT: Inclusion of cardiovascular magnetic resonance examination in the diagnostic and risk-evaluation algorithms in patients with heart failure with preserved ejection fraction should be considered in clinical practice and future studies. KEY POINTS: • Myocardial fibrosis is a common pathological process in heart failure with preserved ejection fraction. • A higher myocardial fibrosis burden on cardiac magnetic resonance predicts a poor prognosis in patients with heart failure with preserved ejection fraction. • Evaluation of myocardial fibrosis may be useful in patients with heart failure with preserved ejection fraction for risk stratification and treatment guidance.

Transcriptome analysis reveals dysregulation of inflammatory and neuronal function in dorsal root ganglion of paclitaxel-induced peripheral neuropathy rats.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most common side-effect of anti-cancer therapy. To date, there are no clinically effective analgesics that could prevent and treat CIPN. However, the exact pathogenesis of CIPN is still unclear. In the present study, we use the paclitaxel-induced peripheral neuropathy (PIPN) model, aiming to better understand the transcriptomic level of the Dorsal root ganglia (DRG) neurons in rats with PIPN. mRNA from each DRG sample was reverse transcribed to cDNA and sequenced using next-generation high throughput sequencing technology. Quantitative RT-PCR verification was used to confirm the identified Differentially expressed genes (DEGs) in the DRG of PIPN rats. RNAseq results have identified 384 DEGs (adjusted P-value < 0.05; fold change ≥ 2) in the DRG of rats 14 days after paclitaxel injection in total, including 97 up-regulated genes, and 287 down-regulated genes. GO analysis revealed that these DEGs were majorly involved in neuropeptide activity, chemokine receptor activity, defense response, and inflammatory response. Kyoto Encyclopedia of Gene and Genomes analysis showed that neuroactive ligand-receptor interaction and cytokine-cytokine receptor interaction were involved in sensory neurons of rats with PIPN. Besides, comparison analysis identified that 11 DEGs in the PIPN model are shared with either inflammatory pain (Ces1d, Cfd, Retn, and Fam150b) or neuropathic pain (Atf3, Csrp3, Ecel1, Gal, Sprr1a, Tgm1, and Vip). Quantitative RT-PCR results also confirmed the validation of the RNAseq data. These results suggested that neuroactive ligand-receptor interaction and cytokine-cytokine receptor interaction are majorly involved in sensory neurons of rats with PIPN. Immune, inflammatory responses and neuron functional changes are the major pathogenesis of PIPN. Paclitaxel-induced peripheral neuropathy has shared characteristics with both inflammatory pain and neuropathic pain.

20.67%-Efficiency Inorganic CsPbI3 Solar Cells Enabled by Zwitterion Ion Interface Treatment.

All-inorganic CsPbI3 perovskite solar cells (PSCs) have been extensively studied due to their high thermal stability and unprecedented rise in power conversion efficiency (PCE). Recently, the champion PCE of CsPbI3 PSCs has reached up to 21%; however, it is still much lower than that of organic-inorganic hybrid PSCs. Interface modification to passivate surface defects and minimize charge recombination and trapping is important to further improve the efficiency of CsPbI3 PSCs. Herein, a new zwitterion ion is deposited at the interface between electron transporting layer (ETL) and perovskite layer to passivate the defects therein. The zwitterion ions can not only passivate oxygen vacancy (VO ) and iodine vacancy (VI ) defects, but also improve the band alignment at the ETL-perovskite interface. After the interface treatment, the PCE of CsPbI3 device reaches up to 20.67%, which is among the highest values of CsPbI3 PSCs so far. Due to the defect passivation and hydrophobicity improvement, the PCE of optimized device remains 94% of its original value after 800 h storing under ambient condition. These results provide an efficient way to improve the quality of ETL-perovskite interface by zwitterion ions for achieving high performance inorganic CsPbI3 PSCs.

HSV-1 infection-induced herpetic neuralgia involves a CCL5/CCR5-mediated inflammation mechanism.

Herpetic-related neuralgia (HN) caused by varicella-zoster virus (VZV) infection is one of the most typical and common neuropathic pain in the clinic. However, the potential mechanisms and therapeutic approaches for the prevention and treatment of HN are still unclear. This study aims to provide a comprehensive understanding of the molecular mechanisms and potential therapeutic targets of HN. We used an HSV-1 infection-induced HN mouse model and screened the differentially expressed genes (DEGs) in the DRG and spinal cord using an RNAseq technique. Moreover, bioinformatics methods were used to figure out the signaling pathways and expression regulation patterns of the DEGs enriched. In addition, quantitative real-time RT-PCR and western blot were carried out to further confirm the expression of DEGs. HSV-1 inoculation in mice resulted in mechanical allodynia, thermal hyperalgesia, and cold allodynia, following the infection of HSV-1 in both DRG and spinal cord. Besides, HSV-1 inoculation induced an up-regulation of ATF3, CGRP, and GAL in DRG and activation of astrocytes and microglia in the spinal cord. Moreover, 639 genes were upregulated, 249 genes were downregulated in DRG, whereas 534 genes were upregulated and 12 genes were downregulated in the spinal cord of mice 7 days after HSV-1 inoculation. GO and KEGG enrichment analysis suggested that immune responses and cytokine-cytokine receptor interaction are involved in DRG and spinal cord neurons in mice after HSV-1 infection. In addition, CCL5 and its receptor CCR5 were significantly upregulated in DRG and spinal cord upon HSV-1 infection in mice. And blockade of CCR5 exhibited a significant analgesic effect and suppressed the upregulation of inflammatory cytokines in DRG and spinal cord induced by HSV-1 infection in mice. HSV-1 infection-induced allodynia and hyperalgesia in mice through dysregulation of immune response and cytokine-cytokine receptor interaction mechanism. Blockade of CCR5 alleviated allodynia and hyperalgesia probably through the suppression of inflammatory cytokines. Therefore, CCR5 could be a therapeutic target for the alleviation of HSV-1 infection-induced HN.

Crystallization Regulation by Self-Assembling Liquid Crystal Template Enables Efficient and Stable Perovskite Solar Cells.

It is found that the disordered growth of bottom perovskite film deteriorates the buried interface of perovskite solar cells (PSCs), so developing a new material to modify the buried interface for regulating the crystal growth and defect passivation is an effective approach for improving the photovoltaic performance of PSCs. Here, we developed a new ionic liquid crystal (ILC, 1-Dodecyl-3-methylimidazolium tetrafluoroborate) as both crystal regulator and defect passivator to modify the buried interface of PSCs. The high lattice matching between this ILC and perovskite promotes preferential growth of perovskite film along [001] direction, while the oriented ILC with mesomorphic phase has a strong chemical interaction with perovskite to passivate the interface defect, as a result, the modified buried interface exhibits suppressed defects, improved band alignment, reduced nonradiative recombination losses, and enhanced charge extraction. The ILC-modified PSC delivers a power conversion efficiency of 24.92 % and maintains 94 % of the original value after storage in ambient for 3000 h.

Primary adult sellar SMARCB1/INI1-deficient tumor represents a subtype of atypical teratoid/rhabdoid tumor.

Loss of function in SMARCB1/INI1 has been observed in a group of malignancies collectively defined as SMARCB1/INI1-deficient neoplasms. Primary intracranial SMARCB1/INI1-deficient tumors in adults are extremely rare. We collected eight primary adult sellar SMARCB1/INI1-deficient tumors to study their clinicopathological and (epi)genetic characteristics. We performed a comprehensive assessment of the clinical, radiological, morphological and immunohistochemical features. FISH analysis for the SMARCB1 locus and target exome sequencing for 425 cancer relevant genes were performed. Furthermore, six bona fide proximal epithelioid sarcoma (PES), fourteen atypical teratoid/rhabdoid tumors (ATRT) in brain and five pediatric poorly differentiated chordomas (PDC) in the clivus were collected for comparative analysis of differential diagnostic maker expression and DNA methylation profile. The median age was 47.1 years, ranging from 26 to 73 years. On morphology, tumors were characterized by sheets of monomorphic larger epithelioid-like cells, in two cases with rhabdoid cells. "Stag-horn" vasculatures were observed in five cases. The loss of INI1 protein expression, co-expression of epithelial makers and mesenchymal markers were observed in all cases. CD34 expression was observed in six cases. Heterozygous deletion of SMARCB1/INI1 was confirmed using FISH in six cases. The results of target exome sequencing showed three patients harbored heterozygous point mutations in SMARCB1. The epigenetic features of the primary adult sellar SMARCB1/INI1-deficient tumors resembled the ATRT-MYC subgroup, but clustered apart from PES and PDC. Based on epigenetic characteristics, primary adult sellar SMARCB1/INI1-deficient tumors represent a subtype of ATRT with similar epigenetic characteristics of ATRT-MYC subgroup. Our findings suggest that DNA methylation profiling should be utilized for differential diagnosis for the majority of epithelioid sarcoma and (sellar) rhabdoid tumor.

SARS-CoV-2, SARS-CoV, and MERS-CoV encode circular RNAs of spliceosome-independent origin.

Circular RNAs (circRNAs) are a newly recognized component of the transcriptome with critical roles in autoimmune diseases and viral pathogenesis. To address the importance of circRNA in RNA viral transcriptome, we systematically identified and characterized circRNAs encoded by the RNA genomes of betacoronaviruses using both bioinformatical and experimental approaches. We predicted 351, 224, and 2764 circRNAs derived from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus, respectively. We experimentally identified 75 potential SARS-CoV-2 circRNAs from RNA samples extracted from SARS-CoV-2-infected Vero E6 cells. A systematic comparison of viral and host circRNA features, including abundance, strand preference, length distribution, circular exon numbers, and breakpoint sequences, demonstrated that coronavirus-derived circRNAs had a spliceosome-independent origin. We further showed that back-splice junctions (BSJs) captured by inverse reverse-transcription polymerase chain reaction have different level of resistance to RNase R. Through northern blotting with a BSJ-spanning probe targeting N gene, we identified three RNase R-resistant bands that represent SARS-CoV-2 circRNAs that are detected cytoplasmic by single-molecule and amplified fluorescence in situ hybridization assays. Lastly, analyses of 169 sequenced BSJs showed that both back-splice and forward-splice junctions were flanked by homologous and reverse complementary sequences, including but not limited to the canonical transcriptional regulatory sequences. Our findings highlight circRNAs as an important component of the coronavirus transcriptome, offer important evaluation of bioinformatic tools in the analysis of circRNAs from an RNA genome, and shed light on the mechanism of discontinuous RNA synthesis.

Multi-lesion radiomics of PET/CT for non-invasive survival stratification and histologic tumor risk profiling in patients with lung adenocarcinoma.

OBJECTIVES: This study investigates the ability of machine learning (ML) models trained on clinical data and 2-deoxy-2-[18F]fluoro-D-glucose(FDG) positron emission tomography/computed tomography (PET/CT) radiomics to predict overall survival (OS), tumor grade (TG), and histologic growth pattern risk (GPR) in lung adenocarcinoma (LUAD) patients. METHODS: A total of 421 treatment-naive patients with histologically-proven LUAD and available FDG PET/CT imaging were retrospectively included. Four cohorts were assessed for predicting 4-year OS (n = 276), 3-year OS (n = 280), TG (n = 298), and GPR (n = 265). FDG-avid lesions were delineated, and 2082 radiomics features were extracted and combined with endpoint-specific clinical parameters. ML models were built for the prediction of 4-year OS (M4OS), 3-year OS (M3OS), tumor grading (MTG), and histologic growth pattern risk (MGPR). A 100-fold Monte Carlo cross-validation with 80:20 training to validation split was employed as a performance evaluation for all models. The association between the M4OS and M3OS predictions with OS was assessed by the Kaplan-Meier survival analysis. RESULTS: The area under the receiver operator characteristics curve (AUC) was the highest for M4OS (AUC 0.88, 95% confidence interval (CI) 86.7-88.7), followed by M3OS (AUC 0.84, CI 82.9-84.9), while MTG and MGPR performed equally well (AUC 0.76, CI 74.4-77.9, CI 74.6-78, respectively). Predictions of M4OS (hazard ratio (HR) -2.4, CI -2.47 to -1.64, p < 0.05) and M3OS (HR -2.36, CI -2.79 to -1.93, p < 0.05) were independently associated with OS. CONCLUSION: ML models are able to predict long-term survival outcomes in LUAD patients with high accuracy. Furthermore, histologic grade and predominant growth pattern risk can be predicted with satisfactory accuracy. KEY POINTS: • Machine learning models trained on pre-therapeutic PET/CT radiomics enable highly accurate long-term survival prediction of patients with lung adenocarcinoma. • Highly accurate survival predictions are achieved in lung adenocarcinoma patients despite heterogenous histologies and treatment regimens. • Radiomic machine learning models are able to predict lung adenocarcinoma tumor grade and histologic growth pattern risk with satisfactory accuracy.

Hydrazide Derivatives for Defect Passivation in Pure CsPbI3 Perovskite Solar Cells.

All-inorganic CsPbI3 perovskite presents preeminent chemical stability and a desirable band gap as the front absorber for perovskite/silicon tandem solar cells. Unfortunately, CsPbI3 perovskite solar cells (PSCs) still show low efficiency due to high density of defects in solution-prepared CsPbI3 films. Herein, three kinds of hydrazide derivatives (benzoyl hydrazine (BH), formohydrazide (FH) and benzamide (BA)) are designed to reduce the defect density and stabilize the phase of CsPbI3 . Calculation and characterization results corroborate that the carboxyl and hydrazine groups in BH form strong chemical bonds with Pb2+ ions, resulting in synergetic double coordination. In addition, the hydrazine group in the BH also forms a hydrogen bond with iodine to assist the coordination. Consequently, a high efficiency of 20.47 % is achieved, which is the highest PCE among all pure CsPbI3 -based PSCs reported to date. In addition, an unencapsulated device showed excellent stability in ambient air.

p-Type Carbon Dots for Effective Surface Optimization for Near-Record-Efficiency CsPbI2 Br Solar Cells.

Interface modification to minimize charge recombination and trapping for efficient charge transport is crucial for the performance of perovskite solar cells (PSCs). Herein, functionalized p-type blue carbon dots (B-CDs) are ventured as an interface passivation layer to enhance the efficiency and long-term stability of all-inorganic CsPbI2 Br PSCs. It is found that first the blue carbon dots with abundant NH, CN, CO, and CO functional groups effectively passivate defects by reacting with I- and Pb2+ ions in the perovskite through hydrogen and coordinative bonds. Second, the p-type B-CDs modifiers form a P-N junction with the n-type perovskite to provide efficient pathways for hole transfer and electron blocking. Third, the B-CDs increase the hydrophobicity of the perovskite film to improve the stability of CsPbI2 Br PSCs. With the above advantages, the CsPbI2 Br PSC with B-CDs modification shows an efficiency as high as 16.76%, one of the highest for its type. In addition, the modification renders significant improvement of air and light stability, with 95.33% of the initial PCE retained after storage in the ambient environment for 1000 h. This work demonstrates the great potential of B-CDs application in perovskite-based optoelectronic devices.

Intravoxel Incoherent Motion Magnetic Resonance Imaging for Prediction of Induction Chemotherapy Response in Locally Advanced Hypopharyngeal Carcinoma: Comparison With Model-Free Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: Multiparametric intravoxel incoherent motion (IVIM) provides diffusion and perfusion information for the treatment prediction of cancer. However, the superiority of IVIM over dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in locally advanced hypopharyngeal carcinoma (LAHC) remains unclear. PURPOSE: To compare the diagnostic performance of IVIM and model-free DCE in assessing induction chemotherapy (IC) response in patients with LAHC. STUDY TYPE: Prospective. POPULATION: Forty-two patients with LAHC. FIELD STRENGTH/SEQUENCE: 3.0 T MRI, including IVIM (12 b values, 0-800 seconds/mm2 ) with a single-shot echo planar imaging sequence and DCE-MRI with a volumetric interpolated breath-hold examination sequence. IVIM MRI is a commercially available sequence and software for calculation and analysis from vendor. ASSESSMENT: The IVIM-derived parameters (diffusion coefficient [D], pseudodiffusion coefficient [D*], and perfusion fraction [f]) and DCE-derived model-free parameters (Wash-in, time to maximum enhancement [Tmax], maximum enhancement [Emax], area under enhancement curve [AUC] over 60 seconds [AUC60 ], and whole area under enhancement curve [AUCw ]) were measured. At the end of IC, patients with complete or partial response were classified as responders according to the Response Evaluation Criteria in Solid Tumors. STATISTICAL TESTS: The differences of parameters between responders and nonresponders were assessed using Mann-Whitney U tests. The performance of parameters for predicting IC response was evaluated by the receiver operating characteristic curves. RESULTS: Twenty-three (54.8%) patients were classified as responders. Compared with nonresponders, the perfusion parameters D*, f, f × D*, and AUCw were significantly higher whereas Wash-in was lower in responders (all P-values <0.05). The f × D* outperformed other parameters, with an AUC of 0.84 (95% confidence interval [CI]: 0.69-0.93), sensitivity of 79.0% (95% CI: 54.4-93.9), and specificity of 82.6% (95% CI: 61.2-95.0). DATA CONCLUSION: The IVIM MRI technique may noninvasively help predict the IC response before treatment in patients with LAHC. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Europium and Acetate Co-doping Strategy for Developing Stable and Efficient CsPbI2 Br Perovskite Solar Cells.

All-inorganic perovskite solar cells have developed rapidly in the last two years due to their excellent thermal and light stability. However, low efficiency and moisture instability limit their future commercial application. The mixed-halide inorganic CsPbI2 Br perovskite with a suitable bandgap offers a good balance between phase stability and light harvesting. However, high defect density and low carrier lifetime in CsPbI2 Br perovskites limit the open-circuit voltage (Voc < 1.2 V), short-circuit current density (Jsc < 15 mA cm-2 ), and fill factor (FF < 75%) of CsPbI2 Br perovskite solar cells, resulting in an efficiency below 14%. For the first time, a CsPbI2 Br perovskite is doped by Eu(Ac)3 to obtain a high-quality inorganic perovskite film with a low defect density and long carrier lifetime. A high efficiency of 15.25% (average efficiency of 14.88%), a respectable Voc of 1.25 V, a reasonable Jsc of 15.44 mA cm-2 , and a high FF of 79.00% are realized for CsPbI2 Br solar cells. Moreover, the CsPbI2 Br solar cells with Eu(Ac)3 doping demonstrate excellent air stability and maintain more than 80% of their initial power conversion efficiency (PCE) values after aging in air (relative humidity: 35-40%) for 30 days.

The Role of Radiotherapy and Surgery in the Management of Aggressive Vertebral Hemangioma: A Retrospective Study of 20 Patients.

BACKGROUND Vertebral hemangioma is usually a benign and asymptomatic tumor of blood vessels, but can be aggressive (symptomatic) with expansion, pain, and spinal cord compression. The aim of this study was to review the effects of radiotherapy, surgery, and other treatment approaches in patients with aggressive vertebral hemangioma. MATERIAL AND METHODS Retrospective clinical review included 20 patients who underwent radiotherapy as their first-line treatment for aggressive vertebral hemangioma with mild or slowly developing neurological deficit. External radiation was divided into 20-25 fractions with a total dose of 40-50 Gy. Minimum clinical follow-up after treatment was 20 months. RESULTS The 20 patients included eight men and 12 women (mean age, 46.6 years), with aggressive vertebral hemangioma located in the cervical, thoracic, and lumbar vertebrae in four, 14, and two patients, respectively. Following radiotherapy treatment, 65.0% of patients (13/20) were symptom-free, without recurrence or malignant transformation at the time of last clinical follow-up (average, 75.2 months). Due to minor post-radiation vertebral re-ossification, two of the 13 patients who were initially symptom-free after radiotherapy requested percutaneous vertebroplasty. A further seven patients required surgery after radiotherapy, due to increasing neurological deficit in three patients, and persistent neurological deficit in four patients. At the last follow-up (average, 63.6 months), six patients were symptom-free, and one patient still had slight residual symptoms. CONCLUSIONS Radiotherapy was a safe and effective treatment choice for aggressive vertebral hemangioma, but in case with severe spinal cord compression and neurological deficit, surgical intervention was required.

Seasonal Hydrological Loading in Southern Tibet Detected by Joint Analysis of GPS and GRACE.

In southern Tibet, ongoing vertical and horizontal motions due to the collision between India and Eurasia are monitored by large numbers of global positioning system (GPS) continuous and campaign sites installed in the past decade. Displacements measured by GPS usually include tectonic deformation as well as non-tectonic, time-dependent signals. To estimate the regional long-term tectonic deformation using GPS more precisely, seasonal elastic deformation signals associated with surface loading must be removed from the observations. In this study, we focus on seasonal variation in vertical and horizontal motions of southern Tibet by performing a joint analysis of GRACE (Gravity Recovery and Climate Experiment) and GPS data, not only using continuous sites but also GPS campaign-mode sites. We found that the GPS-observed and GRACE-modeled seasonal oscillations are in good agreements, and a seasonal displacement model demonstrates that the main reason for seasonal variations in southern Tibet is from the summer monsoon and its precipitation. The biggest loading appears from July to August in the summer season. Vertical deformations observed by GPS and modeled by GRACE are two to three times larger than horizontal oscillations, and the north components demonstrate larger amplitudes than the east components. We corrected the GPS position time series using the GRACE-modeled seasonal variations, which gives significant reductions in the misfit and weighted root-mean-squares (WRMS). Misfit (χ2 divided by degree of freedom) reductions for campaign sites range between 20% and 56% for the vertical component, and are much smaller for the horizontal components. Moreover, time series of continuous GPS (cGPS) sites near the 2015 Nepal earthquakes must be corrected using appropriate models of seasonal loading for analyzing postseismic deformation to avoid biasing estimates of the postseismic relaxation.

Impaired intestinal calcium absorption in protein 4.1R-deficient mice due to altered expression of plasma membrane calcium ATPase 1b (PMCA1b).

Protein 4.1R was first identified in the erythrocyte membrane skeleton. It is now known that the protein is expressed in a variety of epithelial cell lines and in the epithelia of many tissues, including the small intestine. However, the physiological function of 4.1R in the epithelial cells of the small intestine has not so far been explored. Here, we show that 4.1R knock-out mice exhibited a significantly impaired small intestinal calcium absorption that resulted in secondary hyperparathyroidism as evidenced by increased serum 1,25-(OH)2-vitamin D3 and parathyroid hormone levels, decreased serum calcium levels, hyperplasia of the parathyroid, and demineralization of the bones. 4.1R is located on the basolateral membrane of enterocytes, where it co-localizes with PMCA1b (plasma membrane calcium ATPase 1b). Expression of PMCA1b in enterocytes was decreased in 4.1(-/-) mice. 4.1R directly associated with PMCA1b, and the association involved the membrane-binding domain of 4.1R and the second intracellular loop and C terminus of PMCA1b. Our findings have enabled us to define a functional role for 4.1R in small intestinal calcium absorption through regulation of membrane expression of PMCA1b.