Single-cell transcriptome and metagenome profiling reveals the genetic basis of rumen functions and convergent developmental patterns in ruminants.

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.

Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

Insect fungal pathogens secrete a cell wall-associated glucanase that acts to help avoid recognition by the host immune system.

Fungal insect pathogens have evolved diverse mechanisms to evade host immune recognition and defense responses. However, identification of fungal factors involved in host immune evasion during cuticular penetration and subsequent hemocoel colonization remains limited. Here, we report that the entomopathogenic fungus Beauveria bassiana expresses an endo-ß-1,3-glucanase (BbEng1) that functions in helping cells evade insect immune recognition/ responses. BbEng1 was specifically expressed during infection, in response to host cuticle and hemolymph, and in the presence of osmotic or oxidative stress. BbEng1 was localized to the fungal cell surface/ cell wall, where it acts to remodel the cell wall pathogen associated molecular patterns (PAMPs) that can trigger host defenses, thus facilitating fungal cell evasion of host immune defenses. BbEng1 was secreted where it could bind to fungal cells. Cell wall ß-1,3-glucan levels were unchanged in ΔBbEng1 cells derived from in vitro growth media, but was elevated in hyphal bodies, whereas glucan levels were reduced in most cell types derived from the BbEng1 overexpressing strain (BbEng1OE). The BbEng1OE strain proliferated more rapidly in the host hemocoel and displayed higher virulence as compared to the wild type parent. Overexpression of their respective Eng1 homologs or of BbEng1 in the insect fungal pathogens, Metarhizium robertsii and M. acridum also resulted in increased virulence. Our data support a mechanism by which BbEng1 helps the fungal pathogen to evade host immune surveillance by decreasing cell wall glucan PAMPs, promoting successful fungal mycosis.

Hypercholesterolemia Is Associated With Dysregulation of Lipid Metabolism and Poor Prognosis in Primary Biliary Cholangitis.

BACKGROUND & AIMS: Hypercholesterolemia is frequently diagnosed in patients with primary biliary cholangitis (PBC). However, its association with the prognosis and lipid metabolism is unknown. In this study, we aimed to investigate the prognostic value of baseline total cholesterol (TC) levels in PBC and characterized the associated lipid metabolism. METHODS: Five hundred and thirty-one patients with PBC without prior cirrhosis-related complications were randomly divided into the derivation and validation cohorts at a ratio of 7:3. Complete clinical data were obtained and analyzed. The endpoints were defined as liver-related death, liver transplantation, and cirrhosis-related complications. Lipidomics was performed in 89 patients and 28 healthy controls. RESULTS: Baseline TC was independently associated with poor liver-related outcomes, and adjusted C-statistics were 0.80 (95% confidence interval [CI]: 0.74-0.85) and 0.88 (95% CI: 0.78-0.91) in the derivation and validation cohorts, respectively. The predictive ability of TC for disease outcomes was stable over time and comparable with the Globe score. The 200 mg/dL cut-off optimally divided patients into low- and high-TC groups. A combination of TC and Globe score provided a more accurate stratification of patients into risk subgroups. Lipidomics indicated an up-regulation of lipid families in high-TC patients. Pathway analysis of 66 up-regulated lipids revealed the dysregulation of glycerophospholipid and sphingolipid metabolism in high-TC patients, which were associated with poor liver-related outcomes. CONCLUSIONS: Our results indicate that patients with PBC having baseline TC levels above 200 mg/dL have unique lipidome characteristics and are at a higher risk of poor liver-related outcomes.

Low-intensity pulsed ultrasound activated the anti-tumor immunity by irradiating the spleen of mice in 4 T-1 breast cancer.

Tumor immunotherapy is booming around the world. However, strategies to activate the immune system and alleviate the immunosuppression still need to be refined. Here, we demonstrate for the first time that low-intensity pulsed ultrasound (LIPUS, spatial average time average intensity (Isata) is 200 mW/cm2, frequency is 0.3 MHz, repetition frequency is 1 kHz, and duty cycle is 20%) triggers the immune system and further reverses the immunosuppressive state in the mouse models of breast cancer by irradiating the spleen of mice. LIPUS inhibited tumor growth and extended survival in mice with 4 T-1 tumors. Further studies had previously shown that LIPUS enhanced the activation of CD4+ and CD8+ T cells in the spleen and led to significant changes in cytokines, as well as induced upregulation of mRNA levels involved in multiple immune regulatory pathways in the spleen. In addition, LIPUS promoted tumor-infiltrating lymphocyte accumulation and CD8+ T cell activation and improved the dynamics of cytokines/chemokines in the tumor microenvironment, resulting in a reversal of the immunosuppressive state of the tumor microenvironment. These results suggest a novel approach to activate the immune response by irradiating the spleen with LIPUS.

Cross-domain heterogeneous metasurface inverse design based on a transfer learning method.

In this Letter, a transfer learning method is proposed to complete design tasks on heterogeneous metasurface datasets with distinct functionalities. Through fine-tuning the inverse design network and freezing the parameters of hidden layers, we successfully transfer the metasurface inverse design knowledge from the electromagnetic-induced transparency (EIT) domain to the three target domains of EIT (different design), absorption, and phase-controlled metasurface. Remarkably, in comparison to the source domain dataset, a minimum of only 700 target domain samples is required to complete the training process. This work presents a significant solution to lower the data threshold for the inverse design process and provides the possibility of knowledge transfer between different domain metasurface datasets.

Facet-Dependent Photocatalytic Behavior of Rutile TiO2 for the Degradation of Volatile Organic Compounds: In Situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy and Density Functional Theory Investigations.

In this study, a custom rutile titanium dioxide (TiO2) photocatalyst with a single exposed surface was utilized to investigate the facet-dependent photocatalytic mechanism of toluene. The degradation of toluene was dynamically monitored using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) technology coupled with theoretical calculations. The findings demonstrated that the photocatalytic degradation rate on the TiO2 (001) surface was nearly double that observed on the TiO2 (110) surface. This remarkable enhancement can be attributed to the heightened stability in the adsorption of toluene molecules and the concurrent reduction in the energy requirement for the ring-opening process of benzoic acid on the TiO2 (001) surface. Moreover, the TiO2 (001) surface generated a greater number of reactive oxygen species (ROS), thereby promoting the separation of photogenerated charge carriers and concurrently diminishing their recombination rates, amplifying the efficiency of photocatalysis. This research provides an innovative perspective for a more comprehensive understanding of the photocatalytic degradation mechanism of TiO2 and presents promising prospects for significant applications in environmental purification and energy fields.

Whole-tumor histogram analysis of postcontrast T1-weighted and apparent diffusion coefficient in predicting the grade and proliferative activity of adult intracranial ependymomas.

PURPOSE: To investigate the value of histogram analysis of postcontrast T1-weighted (T1C) and apparent diffusion coefficient (ADC) images in predicting the grade and proliferative activity of adult intracranial ependymomas. METHODS: Forty-seven adult intracranial ependymomas were enrolled and underwent histogram parameters extraction (including minimum, maximum, mean, 1st percentile (Perc.01), Perc.05, Perc.10, Perc.25, Perc.50, Perc.75, Perc.90, Perc.95, Perc.99, standard deviation (SD), variance, coefficient of variation (CV), skewness, kurtosis, and entropy of T1C and ADC) using FireVoxel software. Differences in histogram parameters between grade 2 and grade 3 adult intracranial ependymomas were compared. Receiver operating characteristic curves and logistic regression analyses were conducted to evaluate the diagnostic performance. Spearman's correlation analysis was used to evaluate the relationship between histogram parameters and Ki-67 proliferation index. RESULTS: Grade 3 intracranial ependymomas group showed significantly higher Perc.95, Perc.99, SD, variance, CV, and entropy of T1C; lower minimum, mean, Perc.01, Perc.05, Perc.10, Perc.25, Perc.50 of ADC; and higher CV and entropy of ADC than grade 2 intracranial ependymomas group (all p < 0.05). Entropy (T1C) and Perc.10 (ADC) had a higher diagnostic performance with AUCs of 0.805 and 0.827 among the histogram parameters of T1C and ADC, respectively. The diagnostic performance was improved by combining entropy (T1C) and Perc.10 (ADC), with an AUC of 0.857. Significant correlations were observed between significant histogram parameters of T1C (r = 0.296-0.417, p = 0.001-0.044) and ADC (r = -0.428-0.395, p = 0.003-0.038). CONCLUSION: Whole-tumor histogram analysis of T1C and ADC may be a promising approach for predicting the grade and proliferative activity of adult intracranial ependymomas.

Effects of Low-Intensity Pulsed Ultrasound on the Regulation of Free Fatty Acid Release in 3T3-L1 Cells.

OBJECTIVES: To investigate the effects of low-intensity pulsed ultrasound (LIPUS) on the proliferation, differentiation, and tumor necrosis factor-α (TNF-α)-induced lipolysis of 3T3-L1 cells, and to explore the feasibility of regulating the release of free fatty acids (FFA) to prevent lipotoxicity. METHODS: Different intensities (30, 60, 90, and 120 mW/cm2) of LIPUS were applied to 3T3-L1 preadipocytes for different durations (5, 10, 15, 20, 25, and 30 minutes). Appropriate parameters for subsequent experiments were selected by assessing cell viability. The effect of LIPUS on the proliferation and differentiation of 3T3-L1 cells was evaluated by microscope observation, flow cytometry, and lipid content determination. After treated with LIPUS and TNF-α (50 ng/mL), the degree of lipolysis was assessed by measuring the extracellular FFA content. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of relevant genes. RESULTS: Different parameters of LIPUS significantly enhance the viability of 3T3-L1 cells (P < .05), with 20 minutes and 30 mW/cm2 as the most suitable settings. After LIPUS treatment, 3T3-L1 cell proliferation accelerated, apoptosis rate and G1 phase cell proportion decreased, the content of lipid droplets and TG was increased in differentiated cells, while FFA release decreased (P < .05). The expression of PCNA, PPARγ, C/EBPα, Perilipin A mRNA increased, and the expression of TNF-α, ATGL, HSL mRNA decreased (P < .05). CONCLUSIONS: LIPUS could promote the proliferation and differentiation of 3T3-L1 cells and inhibit TNF-α-induced lipolysis, indicating its potential as a therapy for mitigating lipotoxicity caused by decompensated adipocytes.

Long-term repetitive transcranial direct current stimulation in patients with disorders of consciousness: a preliminary study.

OBJECTIVES: To investigate the effects of long-term repetitive transcranial direct current stimulation on patients with DOC in the subacute phase. METHODS: In a randomized, double-blind, controlled study, 33 patients were randomly assigned to the active or sham group, and 28 patients completed the study. Patients in the active group received anodal stimulation over the DLPFC, while patients in the sham group received placebo stimulation (20 min/day, 5 days/week, for 4 weeks). The level of consciousness among patients was assessed with the Coma Recovery Scale-Revised (CRS-R) at baseline and at the end of every week from the first to the fourth week. RESULTS: The CRS-R scores of both the active and sham groups showed a consistent increasing trend over time; however, the treatment effect of the active group was better than that of the sham group. In addition, there was a statistically significant difference in the total CRS-R score between the two groups at weeks 1, 2, 3 and 4. Moreover, 10 patients (71.4%) in the active group and 3 patients (21.4%) in the sham group were regarded as responders. CONCLUSION: Long-term tDCS could improve the level of consciousness of patients with DOC in the subacute stage.

Experience from transport teams on interhospital transfer of patients with extracorporeal membrane oxygenation support: A qualitative study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be a life-saving treatment for patients requiring advanced cardiopulmonary support. Several ECMO centres offer interhospital transport (ECMO IHT) services that involve establishing ECMO teams to initiate ECMO at referring hospitals and then transfer patients to ECMO centres. ECMO IHT is often high risk and complex. Understanding the experience of transport team members is crucial to ensure patient safety and promote quality improvement. AIM: To explore the experiences of transport teams performing ECMO IHT. STUDY DESIGN: A descriptive qualitative methodology was adopted. RESULTS: Thirteen health care professionals who have performed ECMO IHT at a general hospital in China agreed to be interviewed and enrolled in this study. Two investigators conducted face-to-face individual interviews in September-November 2022. All interviews were audio-recorded, transcribed verbatim and analysed using inductive thematic analysis. Three main themes and nine sub-themes were developed: (1) practicing with good organizational management (conducting training programs, cultivating the spirit of good teamwork and developing a standardized transport procedure), (2) dedicated to ensuring patient safety (adequate preparation and regular checking to reduce risk, accurate evaluation to avoid futility and maintaining communication to increase safety) and (3) having confidence despite being uneasy (feeling stressed is common, facing insecurity in transport settings and gaining confidence through practice). CONCLUSIONS: Health care professionals must adequately prepare and assess ECMO IHT to ensure patient safety. Supportive measures should be taken to ensure team members' health and improve patient safety. Good communication and teamwork could improve this challenging task. Further research is required for training programs and establishing standardized transport procedures. RELEVANCE TO CLINICAL PRACTICE: This study presents multi-professional perspectives on the experience of performing ECMO IHT to help management identify what needs to be further developed. With the increasing number of ECMO IHT, promoting its standardization is warranted.

Involvement of IGF1 in endoplasmic reticulum stress contributes to cataract formation through regulating Nrf2/NF-κB signaling.

Endoplasmic reticulum (ER) stress is reportedly involved in the development of ophthalmic diseases. This study aimed to investigate the role and potential mechanism of insulin-like growth factor 1 (IGF1) in ER stress. A mouse cataract model was constructed by subcutaneous injection of sodium selenite, and sh-IGF1 was used to evaluate the effect of silencing IGF1 on cataract progression. Slit-lamp and histological examination of the lens were performed to examine lens damage. The regulatory effects of IGF1 on inflammatory responses, oxidative stress, and ER stress were evaluated using ELISA, reverse transcription-quantitative PCR (RT-qPCR), and immunoblotting analysis. Tunicamycin was used to induce ER stress in the lens of epithelial cells. The NF-E2 related factor-2 (Nrf2) inhibitor ML385 and nuclear factor-κB (NF-κB) agonist diprovocim were used to confirm whether IGF1 regulates inflammation and ER stress through Nrf2/NF-κB signaling. Silencing IGF1 alleviated lens damage and reduced lens turbidity in the cataract mice. Silencing IGF1 inhibited inflammatory response, oxidative stress and ER stress response. Meanwhile, IGF1 was highly expressed in sodium selenite-treated lens epithelial cells. The ER stress agonist tunicamycin suppressed cell viability as well as induced ER stress, oxidative stress and inflammation. Silencing IGF1 increased cell viability, EdU-positive rate and migration. Also, silencing of IGF1 reduced inflammation and ER stress via regulating Nrf2/NF-κB pathway. This study reveals silencing IGF1 attenuated cataract through regulating Nrf2/NF-κB signaling, which shares novel insights into the underlying mechanism of cataract and provides potential therapeutic target for cataract.

Effectiveness of Fenofibrate in Treatment-Naive Patients With Primary Biliary Cholangitis: A Randomized Clinical Trial.

INTRODUCTION: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease, and patients with inadequate response to ursodeoxycholic acid (UDCA) treatment show reduced long-term survival. Recent studies have shown that fenofibrate is an effective off-label therapy for PBC. However, prospective studies on biochemical response including the timing of fenofibrate administration are lacking. This study is aimed to evaluate the efficacy and safety of fenofibrate in UDCA treatment-naive patients with PBC. METHODS: A total of 117 treatment-naive patients with PBC were recruited from the Xijing Hospital for a 12-month randomized, parallel, and open-label clinical trial. Study participants were assigned to receive either UDCA standard dose (UDCA-only group) or fenofibrate at a daily dose of 200 mg in addition to UDCA (UDCA-Fenofibrate group). RESULTS: The primary outcome was biochemical response percentage in patients according to the Barcelona criterion at 12 months. In the UDCA-Fenofibrate group, 81.4% (69.9%-92.9%) of patients achieved the primary outcome and 64.3% (51.9%-76.8%) in the UDCA-only group achieved the primary outcome ( P = 0.048). There was no difference between the 2 groups in noninvasive measures of liver fibrosis and biochemical markers other than alkaline phosphatase at 12 months. Creatinine and transaminases levels in the UDCA-Fenofibrate group increased within the first month, then returned to normal, and remained stable thereafter until the end of the study, even in patients with cirrhosis. DISCUSSION: In this randomized clinical trial in treatment-naive patients with PBC, the combination of fenofibrate and UDCA resulted in a significantly higher biochemical response rate. Fenofibrate seemed to be well-tolerated in patients.

Development of an MRI-Based Comprehensive Model Fusing Clinical, Radiomics and Deep Learning Models for Preoperative Histological Stratification in Intracranial Solitary Fibrous Tumor.

BACKGROUND: Accurate preoperative histological stratification (HS) of intracranial solitary fibrous tumors (ISFTs) can help predict patient outcomes and develop personalized treatment plans. However, the role of a comprehensive model based on clinical, radiomics and deep learning (CRDL) features in preoperative HS of ISFT remains unclear. PURPOSE: To investigate the feasibility of a CRDL model based on magnetic resonance imaging (MRI) in preoperative HS in ISFT. STUDY TYPE: Retrospective. POPULATION: Three hundred and ninety-eight patients from Beijing Tiantan Hospital, Capital Medical University (primary training cohort) and 49 patients from Lanzhou University Second Hospital (external validation cohort) with ISFT based on histopathological findings (237 World Health Organization [WHO] tumor grade 1 or 2, and 210 WHO tumor grade 3). FIELD STRENGTH/SEQUENCE: 3.0 T/T1-weighted imaging (T1) by using spin echo sequence, T2-weighted imaging (T2) by using fast spin echo sequence, and T1-weighted contrast-enhanced imaging (T1C) by using two-dimensional fast spin echo sequence. ASSESSMENT: Area under the receiver operating characteristic curve (AUC) was used to assess the performance of the CRDL model and a clinical model (CM) in preoperative HS in the external validation cohort. The decision curve analysis (DCA) was used to evaluate the clinical net benefit provided by the CRDL model. STATISTICAL TESTS: Cohen's kappa, intra-/inter-class correlation coefficients (ICCs), Chi-square test, Fisher's exact test, Student's t-test, AUC, DCA, calibration curves, DeLong test. A P value <0.05 was considered statistically significant. RESULTS: The CRDL model had significantly better discrimination ability than the CM (AUC [95% confidence interval, CI]: 0.895 [0.807-0.912] vs. 0.810 [0.745-0.874], respectively) in the external validation cohort. The CRDL model can provide a clinical net benefit for preoperative HS at a threshold probability >20%. DATA CONCLUSION: The proposed CRDL model holds promise for preoperative HS in ISFT, which is important for predicting patient outcomes and developing personalized treatment plans. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Host sex disparity and viral genotype dependence of the glycosylation level of small Hepatitis B surface protein in patients with HBeAg-positive chronic Hepatitis B.

BACKGROUND: Hepatitis B surface antigen (HBsAg) consists of six components of large/middle/small HBs proteins (L/M/SHBs) with non-glycosylated (ng)- or glycosylated (g)- isomers at sN146 in their shared S domain. g-SHBs plays a crucial role in hepatitis B virus (HBV) secretion. However, the host and viral factors impacting sN146 status in natural HBV infection remain revealed mainly due to the technical difficulty in quantifying g-SHBs and ng-SHBs in serum samples. METHODS: To establish a standardized Western blot (WB) assay (WB-HBs) for quantifying the SHBs isomers in serum samples of 328 untreated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with genotype B or C HBV infection. The 1.3-mer HBV genotype B or C plasmids were transiently transfected into HepG2 cells for in vitro study. RESULTS: The median level of ng-SHBs was significantly higher than that of g-SHBs (N = 328) (2.6 vs. 2.0 log10, P < 0.0001). The median g-/ng-SHBs ratio in female patients (N = 75) was significantly higher than that of male patients (N = 253) (0.35 vs. 0.31, P < 0.01) and the median g-/ng-SHBs ratio in genotype C patients (N = 203) was significantly higher than that of the genotype B patients (N = 125) (0.33 vs. 0.29, P < 0.0001). CONCLUSIONS: Our findings suggest that the g-/ng-SHBs ratio is host-sex-biased and viral genotype dependent in treatment naïve patients with HBeAg-positive chronic hepatitis B, which indicates the glycosylation of SHBs could be regulated by both host and viral factors. The change of ratio may reflect the fitness of HBV in patients, which deserves further investigation in a variety of cohorts such as patients with interferon or nucleos(t)ide analogues treatment.

Postoperative progression of intracranial grade II-III solitary fibrous tumor/hemangiopericytoma: predictive value of preoperative magnetic resonance imaging semantic features.

BACKGROUND: Preoperative prediction of postoperative tumor progression of intracranial grade II-III hemangiopericytoma is the basis for clinical treatment decisions. PURPOSE: To use preoperative magnetic resonance imaging (MRI) semantic features for predicting postoperative tumor progression in patients with intracranial grade II-III solitary fibrous tumor/hemangiopericytoma (SFT/HPC). MATERIAL AND METHODS: We retrospectively analyzed the preoperative MRI data of 42 patients with intracranial grade II-III SFT/HPC, as confirmed by surgical resection and pathology in our hospital from October 2010 to October 2017, who were followed up for evaluation of recurrence, metastasis, or death. We applied strict inclusion and exclusion criteria and finally included 37 patients. The follow-up time was in the range of 8-120 months (mean = 57.1 months). RESULTS: Single-factor survival analysis revealed that tumor grade (log-rank, P = 0.024), broad-based tumor attachment to the dura mater (log-rank, P = 0.009), a blurred tumor-brain interface (log-rank, P = 0.008), skull invasion (log-rank, P = 0.002), and the absence of postoperative radiotherapy (log-rank, P = 0.006) predicted postoperative intracranial SFT/HPC progression. Multivariate survival analysis revealed that tumor grade (P = 0.009; hazard ratio [HR] = 11.42; 95% confidence interval [CI] = 1.832-71.150), skull invasion (P = 0.014; HR = 5.72; 95% CI = 1.421-22.984), and the absence of postoperative radiotherapy (P = 0.001; HR = 0.05; 95% CI = 0.008-0.315) were independent predictors of postoperative intracranial SFT/HPC progression. CONCLUSION: Broad-based tumor attachment to the dura mater, skull invasion, and blurring of the tumor-brain interface can predict postoperative intracranial SFT/HPC progression.

Ghrelin improves endothelial function and reduces blood pressure in Ang II-induced hypertensive mice: Role of AMPK.

BACKGROUND: Endothelial dysfunction is a major pathophysiology observed in hypertension. Ghrelin, a key regulator of metabolism, has been shown to play protective roles in cardiovascular system. However, whether it has the effect of improving endothelial function and lowering blood pressure in Ang II-induced hypertensive mice remains unclear. METHODS: In this study, hypertension was induced by continuous infusion of Ang II with a subcutaneous osmotic pumps and ghrelin (30 µg/kg/day) was intraperitoneal injection for 4 weeks. Acetylcholine-induced endothelium-dependent relaxation in aortae was measured on wire myograph and superoxide production in mouse aortae was assessed by fluorescence imaging. RESULTS: We found that ghrelin had protective effects on Ang II-induced hypertension by inhibiting oxidative stress, increasing NO production, improving endothelial function, and lowering blood pressure. Furthermore, ghrelin activated AMPK signaling in Ang II-induced hypertension, leading to inhibition of oxidative stress. Compound C, a specific inhibitor of AMPK, reversed the protective effects of ghrelin on the reduction of oxidative stress, the improvement of endothelial function and the reduction of blood pressure. CONCLUSIONS: our findings indicated that ghrelin protected against Ang II-induced hypertension by improving endothelial function and lowering blood pressure partly through activating AMPK signaling. Thus, ghrelin may be a valuable therapeutic strategy for hypertension.

Health-related quality of life assessment instruments for extracorporeal membrane oxygenation survivors: A scoping review.

BACKGROUND AND OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has been successfully and widely used in adult patients for the past 5 years. About 50% of these patients can survive and are discharged from hospitals. Health-related quality of life (HRQOL) is crucial for evaluating survived ECMO patients. This scoping review aims to identify instruments commonly used to measure HRQOL of ECMO survivors and give pertinent instrument characteristics. METHODS: A systematic search was conducted in PubMed, Web of Science, EMBASE (OVID), MEDLINE (OVID), CINAHL (EBSCO), Cochrane Library, and three Chinese databases from January 2012 to December 2021. Two reviewers independently reviewed publication selection and data extraction. RESULTS: Twenty-nine studies met the inclusion criteria. Most studies (93%) were cross-sectional, and the median (or average) follow-up time ranged from 3 months to 9 years. Two prospective studies (7%) followed patients longitudinally until 1 year after discharge. ECMO survivors had poorer long-term HRQOL than the general population. However, it is comparable to or better than patients with other critical or chronic illnesses. Identified HRQOL assessment instruments show four generic HRQOL instruments, one disease-specific HRQOL instrument, and nineteen single-dimensional instruments. Seven instruments were used in more than three articles. SF-36 (86.2%), IES/IES-R (41.4%), and HADS (37.9%) were the most frequently used instruments. CONCLUSION: The timing, frequency, and tools for HRQOL assessment of ECMO survivors are variable. No ECMO-specific HRQOL instrument was developed and validated. Further studies on assessment instruments are warranted. Research is also needed to identify interventions that may enhance HRQOL in ECMO survivors.

Fenofibrate normalizes alkaline phosphatase and improves long-term outcomes in patients with advanced primary biliary cholangitis refractory to ursodeoxycholic acid.

BACKGROUND: Although patients with advanced liver disease have been included in studies evaluating fibrates for the treatment of primary biliary cholangitis (PBC), the frequency of biochemical responses and adverse effects for this group of patients was not reported separately and comprehensively. AIMS: to evaluate the efficacy and safety of additional fenofibrate therapy in patients with advanced and ursodeoxycholic acid (UDCA)-refractory PBC. METHODS: Patients were analyzed retrospectively to determine the clinical therapeutic effects of UDCA with additional fenofibrate therapy versus continued UDCA monotherapy. The liver transplantation (LT)-free survival and the alkaline phosphatase (ALP) normalization rates were estimated using Cox regression analyses and Kaplan-Meier plots with inverse probability of treatment weighting (IPTW). RESULTS: A total of 118 patients were included: 54 received UDCA alone and 64 received UDCA in combination with fenofibrate therapy. In the fenofibrate and UDCA groups, 37% and 11% of patients with advanced and UDCA-refractory PBC, respectively, achieved ALP normalization (P=0.001). Additional fenofibrate therapy improved both LT-free survival and ALP normalization rate after IPTW (hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.07-0.75, P=0.015; and HR: 11.66, 95% CI: 5.02-27.06, P=0.001, respectively). These effects were supported by parallel changes in the rates of liver decompensation and histologic progression, and the United Kingdom (UK)-PBC and Globe risk scores. During the follow-up period, serum levels of ALP and aminotransferase decreased significantly, while total bilirubin, albumin, platelet, serum creatinine, and estimated glomerular filtration rate remained stable in fenofibrate-treated participants. No fenofibrate-related significant adverse events were observed in our cohort. CONCLUSIONS: Additional fenofibrate therapy significantly improved LT-free survival and ALP normalization in patients with advanced and UDCA-refractory PBC. Furthermore, adding-on fenofibrate therapy appeared to be safe and well tolerated in this population.

Towards Automated Microfluidic-based Platforms: Optimizing Hydrogenation Efficiency of Nitrobenzene through π-π Interactions in Pd Nanoparticles on Covalent Organic Frameworks.

Microplatform with timed automata has been leveraged for guiding the preparation of molecules, whereas the requirement of handling expertise and sophisticated instrument is inevitable in combination with heterogeneous catalysis. Here we report a microfluidic-based autolab with open structures, called Put & Play Automated Microplatform (PPAM). It shows the efficient hydrogenation performance of palladium nanoparticles on the triphenylene-based covalent organic frameworks (Pd/TP-COFs) in which the π-π interactions of TP rings in the vicinity of Pd is optimized by easy change-over of catalyst and simple tuning of reactor geometries in PPAM. Using experiment/simulation of the Pd/TP-COFs coating (PCC) and mixing (PCM) across PPAM with different channel sizes, the turnover frequencies are 60 times the commonly used batch reactor, and aniline productivity of 8.8 g h-1 is achieved in 0.09 cm3 . This work will raise awareness about the benefits of the catalyst-loaded microplatform in future materials performance campaigns.