The diagnostic value of [18F]FAPI-42 PET/CT for pulmonary artery masses: comparison with [18F]FDG PET/CT.

OBJECTIVES: To investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) for evaluating pulmonary artery (PA) masses, and compare it with [18F]fluorodeoxyglucose (FDG) PET/CT. METHODS: Participants with clinically suspected PA malignancy were prospectively enrolled and underwent dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging. Visual analysis and semi-quantitative parameters were compared between the two types of radiotracers. The tissue specimen underwent immunohistochemical staining to verify FAP expression in the tissue. RESULTS: Thirty-three patients (18 males/15 females; mean age 53.1 ± 15.4 years) were enrolled. All 21 patients with malignant PA masses were FDG-positive (100%), whereas 20 out of 21 patients were FAPI-positive (95.2%). All 12 patients with benign PA masses were both negative in FDG and FAPI PET. The mean maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) of FAPI and FDG in malignant PA masses were significantly higher than those of benign masses. Although there was no significant difference in SUVmax between FDG and FAPI in malignant PA masses (11.36 vs. 9.18, p = 0.175), the TBR (liver) and TBR (left ventricle) were more favorable for FAPI than for FDG (13.04 vs. 5.17, p < 0.001); (median: 7.75 vs. 2.75, p = 0.007). Immunohistochemical analysis (n = 16) validated that the level of FAP expression corresponded strongly to the uptake of FAPI in PET/CT scans (rs = 0.712, p = 0.002). For clinical management, FAPI PET found more metastatic lesions than FDG PET in 4 patients, with 2 patients upgrading and 1 patient changing treatment decisions. CONCLUSIONS: FAPI PET/CT is feasible in the diagnosis of PA masses. Although not superior to FDG PET/CT, FAPI PET/CT showed better target-to-background contrast. CLINICAL RELEVANCE STATEMENT: This study found that FAPI PET/CT is not superior to FDG PET/CT in diagnosing PA masses, but FAPI PET/CT displays better target-to-background contrast and more positive lesions, which may help improve disease management. KEY POINTS: Pulmonary malignancies lack specificity in clinical manifestations, laboratory tests, and routine imaging examinations. FAPI PET/CT is not diagnostically better than FDG PET/CT but displays better target-to-background contrast and more positive lesions. Dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging improves clinical management of pulmonary artery masses.

Implication of Cerebral Small-Vessel Disease on Perihematomal Edema Progress in Patients With Hypertensive Intracerebral Hemorrhage.

BACKGROUND: Perihematomal edema (PHE) is an important determinant of outcome in spontaneous intracerebral hemorrhage (ICH) due to cerebral small vessel disease (CSVD). However, it is not known to date whether the severity of CSVD is associated with the extent of PHE progression in the acute phase. PURPOSE: To investigate the association between the magnetic resonance imaging (MRI) marker of severe chronic-ischemia cerebral small vessel changes (sciSVC) and PHE growth or hematoma absorption among ICH patients with hypertension. STUDY TYPE: Retrospective. POPULATION: Three hundred and sixty-eight consecutive hypertensive ICH patients without surgical treatment. FIELD STRENGTH/SEQUENCE: 3 T; spin-echo echo-planar imaging-diffusion-weighted imaging (DWI); T2-weighted, fluid-attenuated inversion recovery (FLAIR), T2*-weighted gradient-recalled echo and T1-weighted. ASSESSMENT: The hematoma and PHE volumes at 24 hours and 5 days after symptom onset were measured in 121 patients with spontaneous ICH who had been administered standard medical treatment. Patients were grouped into two categories: those with sciSVC and those without. The imaging marker of sciSVC was defined as white matter hyperintensities (WMHs) Fazekas 2-3 combined cavitating lacunes. STATISTICAL TESTS: Univariable analyses, χ2 test, Mann-Whitney U test, and multiple linear regression. RESULTS: The presence of sciSVC (multiple lacunes and confluent WMH) had a significant negative influence on PHE progress (Beta = -5.3 mL, 95% CI = -10.3 mL to -0.3 mL), and hematoma absorption (Beta = -3.2 mL, 95% CI = -5.9 mL to -0.4 mL) compared to that observed in the absence of sciSVC, as determined by multivariate linear regression analysis. DATA CONCLUSIONS: The presence of sciSVC (multiple lacunes and confluent WMH) negatively influenced hematoma absorption and PHE progress in ICH patients. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

Bilateral versus unilateral balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: To evaluate the safety and efficacy of bilateral balloon pulmonary angioplasty (BPA) as compared with unilateral BPA for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). METHOD: We reviewed 210 consecutive BPA sessions for 92 CTEPH patients, including 124 unilateral BPA sessions and 86 bilateral BPA sessions. Radiation exposure, operation details, lesions characteristics and the occurrence of complications were compared between unilateral BPA and bilateral BPA. 131 BPA sessions with a hemodynamics follow-up were included for efficacy analysis, in which hemodynamics changes were compared. Logistic regression analysis was used to identify factors associated with the occurrence of complications. RESULT: Bilateral BPA treated more lobes, arteries and lesions [3 (2, 4) vs. 2 (1, 3) lobes, p < 0.001; 8 (5.5, 10) vs. 6 (4, 8) vessels, p = 0.003; 9 (7, 12) vs. 8 (5, 10) lesions, p = 0.01] in one single session than unilateral BPA in a comparable operation duration and amount of contrast media given. Overall, the occurrence of complications was similar between bilateral BPA and unilateral BPA [9 (10.5%) vs. 12 (9.7%), p = 0.83]. Hemodynamics effects didn't differ significantly between bilateral BPA and unilateral BPA in a single session [mPAP, - 4.5 ± 8.6 vs. - 3.6 ± 7.3 mmHg, p = 0.52; PVR, - 1.1 (- 3.5, 0.8) vs. - 1.8 (- 5.2, 0.3) Wood units, p = 0.21]. For the initial BPA session, bilateral BPA also treated more lobes, arteries and lesions than unilateral BPA [3 (2, 4) vs. 2 (1, 2) lobes, p < 0.001; 8.0 (5.8, 9.3) vs. 6.0 (4.0, 8.0) vessels, p = 0.04; 9 (6, 12) vs. 7 (4, 10) lesions, p = 0.02]. The occurrence of complications was also similar [5 (13.2%) vs. 5 (9.3%), p = 0.80], even in patients with poor baseline hemodynamics. Univariate regression analysis reveals the number of lobes treated/session, but not bilateral BPA, as predictive factors of complications. CONCLUSION: Bilateral BPA may be safely and effectively performed in patients with CTEPH without increasing operation duration and radiation burden, even in patients with unfavorable baseline hemodynamics.

Improving the imaging diagnostic strategy for pulmonary artery masses based on 18F-FDG PET/CT integrated with CTPA.

OBJECTIVE: To evaluate the diagnostic accuracy of computed tomography pulmonary angiography (CTPA) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for pulmonary artery (PA) masses. METHODS: Of 2889 patients with PA filling defects of PA on CTPA, 79 consecutive patients suspicious for PA malignancy who subsequently underwent 18F-FDG PET/CT were enrolled. All masses were diagnosed on the basis of pathological findings or clinical imaging follow-up. For each mass, morphological CT signs, standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18F-FDG PET/CT were used as diagnostic markers. RESULTS: Expansive growth, irregular margin, invasion, CT contrast uptake, and wall eclipse sign were strongly associated with the malignant nature of masses. The coexistence of at least 5 CT signs perfectly identified malignant masses, whereas the detection of no more than 4 CT signs did not accurately discriminate between the natures of masses. Mean SUVmax, SUVmean, MTV, and TLG values were significantly higher in malignant masses compared to those in benign masses. The diagnostic accuracy of 18F-FDG PET/CT parameters (SUV, MTV, and TLG) was excellent in detecting malignant masses. Among patients with 3 or 4 pathological CT signs, SUVmax > 3.4 significantly increased the identification of malignancies. CONCLUSIONS: CTPA is a useful imaging modality for diagnosing PA masses, especially when at least 5 abnormal CT signs are identified. Similarly, 18F-FDG PET/CT accurately identified malignant masses and provided additional valuable information on diagnostic uncertainties after CTPA.

Effect of Throat Washings on Detection of 2019 Novel Coronavirus.

The 2019 novel coronavirus was detected in self-collected throat washings. The positive testing rate of throat washing was much higher than that of nasopharyngeal swabs. Throat washing is a promising candidate for 2019-nCoV screening and monitoring due to its noninvasiveness and reliability.

Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To systematically review the efficacy and safety of anti-inflammatory agents for patients with major depressive disorders. METHODS: We searched the literature to identify potentially relevant randomised controlled trials (RCTs) up to 1 January 2019. The primary outcome was efficacy, measured by mean changes in depression score from baseline to endpoint. Secondary outcomes included response and remission rates and quality of life (QoL). Safety was evaluated by incidence of classified adverse events. Heterogeneity was examined using the I2 and Q statistic. Pooled standard mean differences (SMDs) and risk ratios (RRs) were calculated. Subgroup meta-analyses were conducted based on type of treatment, type of anti-inflammatory agents, sex, sponsor type and quality of studies. RESULTS: Thirty RCTs with 1610 participants were included in the quantitative analysis. The overall analysis pooling from 26 of the RCTs suggested that anti-inflammatory agents reduced depressive symptoms (SMD -0.55, 95% CI -0.75 to -0.35, I2=71%) compared with placebo. Higher response (RR 1.52, 95% CI 1.30 to 1.79, I2=29%) and remission rates (RR 1.79, 95% CI 1.29 to 2.49, I2=41%) were seen in the group receiving anti-inflammatory agents than in those receiving placebo. Subgroup analysis showed a greater reduction in symptom severity in both the monotherapy and adjunctive treatment groups. Subgroup analysis of non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins and minocyclines, respectively, disclosed significant antidepressant effects for major depressive disorder (MDD). For women-only trials, no difference in changes of depression severity was found between groups. Subanalysis stratified by sponsor type and study quality led to the same outcomes in favour of anti-inflammatory agents in both subgroups. Changes of QoL showed no difference between the groups. Gastrointestinal events were the only significant differences between groups in the treatment periods. CONCLUSIONS: Results of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with MDD and are reasonably safe.

Application of DynaCT angiographic reconstruction in balloon pulmonary angioplasty.

OBJECTIVES: To investigate the feasibility and accuracy of balloon pulmonary angioplasty (BPA) using DynaCT angiographic reconstruction guidance. METHODS: Thirty-four BPAs (23 CTEPH patients) targeting 175 pulmonary arteries were included. Eleven BPAs (2D group) were guided by DSA two-dimensional angiography. Another twenty-three BPAs (3D group) were guided using DynaCT angiographic reconstruction. The volume rendering (VR) method was used to obtain a three-dimensional image of the blood vessels. This image was used as a reference to continue BPA treatment under the guidance of vascular three-dimensional reconstruction technology. Procedure durations and radiation exposure data were compared between the two groups using Mann-Whitney U test. RESULTS: Using the DynaCT angiographic reconstruction technique, more target vessels were treated in a single BPA procedure (5.83 ± 2.33 vs 3.73 ± 1.10 vessels per BPA, p = 0.008) in a shorter operation time (3.58 ± 0.61 vs 4.49 ± 0.91 h, p = 0.002). Overall, the dose area product (DAP) was significantly higher for the 2D group than for the 3D group (13,901.82 ± 5549.69 vs 4682.82 ± 1950.64, p < 0.001). The use of the DynaCT angiographic reconstruction technique to guide BPA required a lower dose of contrast agent (225.22 ± 48.70 vs 292.73 ± 76.82 mL, p = 0.013) and less radiation exposure. CONCLUSIONS: The use of DynaCT angiographic reconstruction guidance in patients undergoing BPA is feasible and accurate. Images of DynaCT angiographic reconstruction may be beneficial for optimizing the operative process in BPA with reduced radiation exposure. KEY POINTS: • BPA guidance by DynaCT angiographic reconstruction is feasible and accurate. • DynaCT angiographic reconstruction may be beneficial for optimizing the operative process. • DynaCT angiographic reconstruction can reduce patient radiation dose due to multi-times of BPA sessions.

Efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine - an updated systematic review and meta-analysis.

BACKGROUND: Migraine is one of the most common neurological disorders that leads to disabilities. However, the conventional drug therapy for migraine might be unsatisfactory at times. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibody (CGRP mAb) for the preventive treatment of episodic migraine, and provide high-quality clinical evidence for migraine therapy. METHODS: A systematic electronic database search was conducted to identify the potentially relevant studies. Two independent authors performed data extraction and quality appraisal. Mean difference (MD) and risk ratio (RR) were pooled for continuous and dichotomous data, respectively. The significance levels, weighted effect sizes and homogeneity of variance were calculated. RESULTS: Eleven high-quality randomized control trials that collectively included 4402 patients were included in this meta-analysis. Compared to placebo group, CGRP mAb therapy resulted in a reduction of monthly migraine days [weighted mean difference (WMD) = - 1.44, 95% CI = (- 1.68,- 1.19)] and acute migraine-specific medication days [WMD = - 1.28, 95% CI = (- 1.66,- 0.90)], with an improvement in 50% responder rate [RR = 1.51, 95% CI = (1.37,1.66)]. In addition, the adverse events (AEs) and treatment withdrawal rates due to AEs were not significantly different between CGRP mAb and placebo groups. Similar efficacy and safety results were obtained for erenumab, fremanezumab, and galcanezumab in subgroup analysis. CONCLUSIONS: The current body of evidence reveals that CGRP mAb is an effective and safe preventive treatment for episodic migraine.

Ultra-broadband infrared metasurface absorber: reply.

This is a reply to the comment "Ultra-broadband infrared metasurface absorber: comment."

Incidence and Predictors of Tracheobronchial Tuberculosis in Pulmonary Tuberculosis: A Multicentre, Large-Scale and Prospective Study in Southern China.

BACKGROUND: Patients with pulmonary tuberculosis (PTB) have a high risk of concomitant tracheobronchial tuberculosis (TBTB), which commonly causes severe complications such as tracheobronchial stenosis. The prevalence and predictors of TBTB in China remain unclear due to the lack of prospective and large-scale studies. OBJECTIVES: To investigate the incidence of TBTB in PTB patients in southern China, and elucidate the predictors of TBTB and related tracheobronchial stenosis. METHODS: We prospectively performed bronchoscopy in PTB patients to diagnose TBTB at four medical centres in southern China from September 2015 to August 2016. Clinical and epidemiological data were recorded and analysed to determine predictors of TBTB and related tracheobronchial stenosis. RESULTS: A total of 345 (23.9%) of the 1,442 PTB patients undergoing bronchoscopy were diagnosed with TBTB. Female sex (OR 2.53), age < 50 years (OR 1.88), living in urban (OR 2.19), diabetes (OR 1.84), coughing (OR 2.61), and symptoms ≥4 weeks (OR 1.66) were predictors of PTB concomitant with TBTB. About 59.7% TBTB patients developed tracheobronchial stenosis, of which 23.3% cases presented severe airway narrowing. Female sex (OR 2.27), age < 50 years (OR 2.11), shortness of breath (OR 1.97), and symptoms ≥4 weeks (OR 1.71) were predictors of TBTB-related tracheobronchial stenosis. CONCLUSIONS: About 23.9% of PTB patients undergoing bronchoscopy present with TBTB in Guangdong province, southern China. Young and middle-aged females with symptoms persisting for ≥4 weeks (the main predictors of TBTB and related tracheobronchial stenosis) should receive bronchoscopy immediately when diagnosed with PTB.

Ultra-broadband infrared metasurface absorber.

By using sub-wavelength resonators, metamaterial absorber shows great potential in many scientific and technical applications due to its perfect absorption characteristics. For most practical applications, the absorption bandwidth is one of the most important performance metrics. In this paper, we demonstrate the design of an ultra-broadband infrared absorber based on metasurface. Compared with the prior work [Opt. Express22(S7), A1713-A1724 (2014)], the proposed absorber shows more than twice the absorption bandwidth. The simulated total absorption exceeds 90% from 7.8 to 12.1 um and the full width at half maximum is 50% (from 7.5 to 12.5 µm), which is achieved by using a single layer of metasurface. Further study demonstrates that the absorption bandwidth can be greatly expanded by using two layers of metasurface, i.e. dual-layered absorber. The total absorption of the dual-layered absorber exceeds 80% from 5.2 to 13.7 um and the full width at half maximum is 95% (from 5.1 to 14.1 µm), much greater than those previously reported for infrared spectrum. The absorption decreases with fluctuations as the incident angle increases but remains quasi-constant up to relatively large angles.

[Refractory pulmonary alveolar proteinosis treated with inhaled granulocyte macrophage colony stimulating factor: a case report and review of the literatures].

OBJECTIVE: To observe the efficacy of granulocyte macrophage colony stimulating factor inhalation therapy for pulmonary alveolar proteinosis (PAP) patients and to improve the understanding of the therapy. METHODS: The clinical data of a patient with autoimmune PAP treated with inhaled granulocyte macrophage colony stimulating factor were described and the literatures were reviewed. RESULTS: This 70-year-old female patient was diagnosed with autoimmune PAP and had been treated with whole lung lavage for 10 times, but only achieved short-term symptomatic relief after each operation. Inhalation of granulocyte macrophage colony stimulating factor was then used after the recurrence of PAP, and a significant improvement in oxygenation and clinical symptoms were abserved. The patient remained stable 4 month after the therapy. CONCLUSION: Treatment with inhalation of granulocyte macrophage colony stimulating factor is safe, effective and economic for patients with PAP, and would be the first choice for the recurrence of autoimmune PAP after whole lung lavage.

Initial timing of alfalfa hay supplementation manipulates blood parameters, rumen gene expression, and epithelial microbiota in pre-weaning lambs.

The present study aimed to investigate the impact of initiating alfalfa supplementation at either 14 or 42 days of age on growth performance, blood parameters, rumen tissue gene expression, and epithelial microbiota in pre-weaning lambs. A total of 42 seven-day-old male Hu lambs (3.88 ± 0.92 kg) were selected for this study. After 7 d of adjustment period, six lambs were slaughtered at 14 d of age to establish a baseline control. The remaining 36 lambs were randomly allocated to two treatment groups, every three lambs were considered a unit, including fed milk replacer, starter pellets, and either alfalfa hay fed at 14 (EAF) or 42 d of age (LAF). Body weight and feed intake were recorded for lamb until 70 d of age. Blood samples, rumen tissue samples, and epithelial microbiota samples were collected from the lambs at 42, 56, and 70 d of age. The results indicated that average daily gain, starter intake, and total dry matter intake were greater in the EAF group compared to the LAF group from 14 to 42 d of age (P < 0.01), but no significant differences from 43 to 70 d of age or during the entire trial. Treatment and age interactively affected the alfalfa intake (P = 0.02) from 43 to 70 d of age. The concentration of serum immunoglobulin A (IgA) (P < 0.01) and the expression of the rumen gene insulin-like growth factor 1 (P < 0.01) were greater in the EAF group compared to the LAF group at 42 d of age. Furthermore, the concentrations of alkaline phosphatase (P = 0.03), albumin (P < 0.01), total protein (P = 0.03), urea (P = 0.04), lipopolysaccharide (P < 0.01), ß-hydroxybutyric acid (P = 0.02), interleukin-1ß (IL-1ß) (P < 0.01), IL-4 (P < 0.01), and tumor necrosis factor α (P < 0.01) were affected by age. The abundance of Prevotella was lower (P < 0.05), whereas Megasphaera (P < 0.05) was greater in the EAF group compared to the LAF group at 42 d of age. The early addition of alfalfa promotes rumen epithelial microbiota colonization. In conclusion, this study demonstrated that alfalfa provision at 14 d of age promotes growth performance in lambs, but this effect disappeared at 43 to 70 d of age. Moreover, provision of alfalfa at 14 d of age enhances the immune response, promotes rumen tissue cell proliferation, and affects dynamical changes of rumen epithelial microbiota. Meanwhile, our findings showed that the rumen undergoes significant physiological challenges during the transition from a liquid diet to a solid diet.

Characterizing mitochondrial features in osteoarthritis through integrative multi-omics and machine learning analysis.

Purpose: Osteoarthritis (OA) stands as the most prevalent joint disorder. Mitochondrial dysfunction has been linked to the pathogenesis of OA. The main goal of this study is to uncover the pivotal role of mitochondria in the mechanisms driving OA development. Materials and methods: We acquired seven bulk RNA-seq datasets from the Gene Expression Omnibus (GEO) database and examined the expression levels of differentially expressed genes related to mitochondria in OA. We utilized single-sample gene set enrichment analysis (ssGSEA), gene set enrichment analysis (GSEA), and weighted gene co-expression network analysis (WGCNA) analyses to explore the functional mechanisms associated with these genes. Seven machine learning algorithms were utilized to identify hub mitochondria-related genes and develop a predictive model. Further analyses included pathway enrichment, immune infiltration, gene-disease relationships, and mRNA-miRNA network construction based on these hub mitochondria-related genes. genome-wide association studies (GWAS) analysis was performed using the Gene Atlas database. GSEA, gene set variation analysis (GSVA), protein pathway analysis, and WGCNA were employed to investigate relevant pathways in subtypes. The Harmonizome database was employed to analyze the expression of hub mitochondria-related genes across various human tissues. Single-cell data analysis was conducted to examine patterns of gene expression distribution and pseudo-temporal changes. Additionally, The real-time polymerase chain reaction (RT-PCR) was used to validate the expression of these hub mitochondria-related genes. Results: In OA, the mitochondria-related pathway was significantly activated. Nine hub mitochondria-related genes (SIRT4, DNAJC15, NFS1, FKBP8, SLC25A37, CARS2, MTHFD2, ETFDH, and PDK4) were identified. They constructed predictive models with good ability to predict OA. These genes are primarily associated with macrophages. Unsupervised consensus clustering identified two mitochondria-associated isoforms that are primarily associated with metabolism. Single-cell analysis showed that they were all expressed in single cells and varied with cell differentiation. RT-PCR showed that they were all significantly expressed in OA. Conclusion: SIRT4, DNAJC15, NFS1, FKBP8, SLC25A37, CARS2, MTHFD2, ETFDH, and PDK4 are potential mitochondrial target genes for studying OA. The classification of mitochondria-associated isoforms could help to personalize treatment for OA patients.

Alfalfa supplementation timing changes the rumen archaeal and fungal community composition and colonization in pre-weaning lambs.

The establishment of the rumen microbiota plays an important role in the rumen development. However, little is known about the effects of alfalfa supplementation time on rumen microbiota establishment. Here, a total of 42 Hu lambs, seven-day-old, were chosen for the study. After a week of adjustment, six lambs were sacrificed to establish a baseline. The remaining 36 lambs were randomly split into two groups: one receiving alfalfa hay at 14 days (EAF), the other at 42 days (LAF), both groups received milk replacer and starter pellets. Introducing alfalfa at 14 days of age significantly improved total dry matter intake between 28 and 42 days (p = 0.04) and average daily gain from both 14 to 28 days (p = 0.04) and 28 to 42 days (p < 0.01), but this effect disappears from 56 to 70 days (p > 0.05). At 42 days, the abundances of Naganishia, Ascochyta, and Neosetophoma in the EAF group were significantly higher (p < 0.05) than those in the LAF group (17.8% vs. 3.97, 10.89% vs. 1.77, and 1.27% vs. 0.09%, respectively). At 56 days, the abundances of Ascochyta, Wallemia, and Aspergillus in the EAF group were significantly lower (p < 0.05) than in the LAF group (3.53% vs. 16.40, 8.78% vs. 18.89, and 2.14% vs. 4.69%). At 70 days, Aspergillus abundance in the EAF group was significantly higher (p < 0.05) than in the LAF group (2.69% vs. 0.85%). The LEfSe analysis showed that Methanobrevibacter_smithii was the archaeal biomarker at 14 days in both groups. Methanobrevibacter_sp_AbM4 was enriched at 56 days in the LAF group. Compared to the LAF group, the specific fungal biomarkers in the EAF group included Sporobolomyces and Bullera at 14 days, Naganishia, Didymella, Cleistothelebolus, and Alloleptosphaeria at 42 days, Ascochyta, Neoascochyta, and Alfaria at 70 days. Correlation analysis results showed strong patterns of association both within and between archaea and fungi, which were influenced by alfalfa supplementation time. In summary, alfalfa supplementation at 14 days of age promotes the growth performance of lambs before weaning, and alfalfa supplementation timing significantly affects rumen archaeal and fungal communities and dynamical changes.

Novel ß-amyloid PET Imaging Study of [18F]92 in Patients with Cognitive Decline.

[18F]-4-((E)-(((E)-4-(2-(2-(2-Fluoroethoxy)ethoxy)ethoxy)benzylidene)-hydrazono)methyl)-N-methylaniline ([18F]92) is a novel positron emission tomography (PET) tracer previously reported to exhibit high binding affinity to aggregated ß-amyloid (Aß). This study aims to report a fully automated radiosynthesis procedure for [18F]92, explore its radioactive distribution in the brains of healthy subjects, and investigate its potential application value in the early diagnosis of Alzheimer's disease (AD). The fully automated radiosynthesis of [18F]92 was performed on the AllinOne module. Thirty one participants were recruited for this study. Dynamic [18F]92 PET imaging was conducted over 0-90 min period to assess time-activity curves (TAC) and standardized uptake value ratio (SUVR) curves in cognitively normal (CN) subjects. All participants were visually classified as either positive (+) or negative (-). Semiquantitative analyses of [18F]92 were performed by calculating SUVRs in different regions of interest. Furthermore, the study analyzed the relationships between global SUVR and plasma AD biomarkers, including Aß42, Aß40, P-tau181, and T-tau. The automated radiosynthesis of [18F]92 was completed within 50 min, yielding a radiochemical purity of greater than 95% and a radiochemical yield of 36 ± 3% (nondecay-corrected). Among the participants, 15 were estimated as Aß (-) and 16 as Aß (+). TACs indicated that [18F]92 rapidly crossed the blood-brain barrier within 10 min, followed by a rapid decrease, which then slowed down in the last 50-90 min. SUVR curves revealed that SUVR values stabilized around 60-70 min after injection and reached an equilibrium between 70 and 90 min, primarily in the cerebral cortex. SUVRs of Aß (+) participants were significantly higher than those of Aß (-) individuals within the cerebral cortex. In addition, Aß42 and the Aß42/Aß40 ratio exhibited negative correlations with global SUVR, while plasma P-tau181 and the P-tau181/T-tau ratio displayed positive correlations with global SUVR. [18F]92 exhibits excellent pharmacokinetic properties in the human brain and can be synthesized automatically on a large scale. [18F]92 is a promising and reliable radiotracer for estimating Aß pathology accumulation, providing valuable assistance in AD diagnosis and guiding clinical trials of therapeutic drugs.

The Effects of Housing on Growth, Immune Function and Antioxidant Status of Young Female Lambs in Cold Conditions.

Cold conditions in northern China during winter may reduce sheep growth and affect their health, especially if they are young, unless housing is provided. We allocated 45 two-month-old female lambs to be housed in an enclosed building, a polytunnel, or kept outdoors, for 28 days. The daily weight gain and scalp and ear skin temperature of outdoor lambs were less than those of lambs that were housed in either a house or polytunnel; however, rectal temperature was unaffected by treatment. There was a progressive change in blood composition over time, and by the end of the experiment, outdoor lambs had reduced total antioxidant capacity (T-AOC), catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) and increased malondialdehyde compared to those in the house or polytunnel. In relation to immune responses in the lambs' serum, in the polytunnel, immunoglobulin A (IgA), tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) were higher and immunoglobulin G (IgG) lower compared with the concentrations in lambs that were outdoors. Over the course of the experiment, genes expressing heat shock proteins and antioxidant enzymes increased in lambs in the outdoor treatment, whereas they decreased in lambs in the indoor treatments. It is concluded that although there were no treatment effects on core body temperature, the trends for progressive changes in blood composition and gene expression indicate that the outdoor lambs were not physiologically stable; hence, they should not be kept outdoors in these environmental conditions for long periods.

Characterizing hedgehog pathway features in senescence associated osteoarthritis through Integrative multi-omics and machine learning analysis.

Purpose: Osteoarthritis (OA) is a disease of senescence and inflammation. Hedgehog's role in OA mechanisms is unclear. This study combines Bulk RNA-seq and scRNA-seq to identify Hedgehog-associated genes in OA, investigating their impact on the pathogenesis of OA. Materials and methods: Download and merge eight bulk-RNA seq datasets from GEO, also obtain a scRNA-seq dataset for validation and analysis. Analyze Hedgehog pathway activity in OA using bulk-RNA seq datasets. Use ten machine learning algorithms to identify important Hedgehog-associated genes, validate predictive models. Perform GSEA to investigate functional implications of identified Hedgehog-associated genes. Assess immune infiltration in OA using Cibersort and MCP-counter algorithms. Utilize ConsensusClusterPlus package to identify Hedgehog-related subgroups. Conduct WGCNA to identify key modules enriched based on Hedgehog-related subgroups. Characterization of genes by methylation and GWAS analysis. Evaluate Hedgehog pathway activity, expression of hub genes, pseudotime, and cell communication, in OA chondrocytes using scRNA-seq dataset. Validate Hedgehog-associated gene expression levels through Real-time PCR analysis. Results: The activity of the Hedgehog pathway is significantly enhanced in OA. Additionally, nine important Hedgehog-associated genes have been identified, and the predictive models built using these genes demonstrate strong predictive capabilities. GSEA analysis indicates a significant positive correlation between all seven important Hedgehog-associated genes and lysosomes. Consensus clustering reveals the presence of two hedgehog-related subgroups. In Cluster 1, Hedgehog pathway activity is significantly upregulated and associated with inflammatory pathways. WGCNA identifies that genes in the blue module are most significantly correlated with Cluster 1 and Cluster 2, as well as being involved in extracellular matrix and collagen-related pathways. Single-cell analysis confirms the significant upregulation of the Hedgehog pathway in OA, along with expression changes observed in 5 genes during putative temporal progression. Cell communication analysis suggests an association between low-scoring chondrocytes and macrophages. Conclusion: The Hedgehog pathway is significantly activated in OA and is associated with the extracellular matrix and collagen proteins. It plays a role in regulating immune cells and immune responses.