The Characterization of Subcutaneous Adipose Tissue in Sunit Sheep at Different Growth Stages: A Comprehensive Analysis of the Morphology, Fatty Acid Profile, and Metabolite Profile.

Adipose tissue is a crucial economically significant trait that significantly influences the meat quality and growth performance of domestic animals. To reveal the changes in adipose tissue metabolism during the growth of naturally grazing sheep, we evaluated the thickness, adipocyte morphology, fatty acid profile, and metabolite profile of subcutaneous adipose tissue (SAT) from naturally grazing Sunit sheep at 6, 18, and 30 months of age (referred to as Mth-6, Mth-18, and Mth-30, respectively). The fat thickness and adipocyte number were significantly increased with the growth of the sheep (p < 0.05), and the increase of which from Mth-18 to Mth-30 was less than that from Mth-6 to Mth-18. Additionally, the alpha-linolenic acid metabolism was enhanced and fatty acid (FA) elongation increased with growth. The metabolomic analysis revealed 76 differentially expressed metabolites (DEMs) in the SAT in different growth stages. Interestingly, we observed elongation of FAs in lipids correlated with sheep growth. Furthermore, the expression of acylcarnitines was downregulated, and fatty acid amides, aspartic acid, acetic acid and phosphocholine were upregulated in Mth-18 and Mth-30 compared to Mth-6. Altogether, the study found that the difference in SAT in Mth-6 was great compared to Mth-18 and Mth-30. An increase in fat deposition via adipocyte proliferation with the growth of the sheep in naturally grazing. The DEMs of acylcarnitines, fatty acid amides, aspartic acid, acetic acid, and phosphocholine emerged as potential key regulators of adipose tissue metabolism. These findings illustrate the variation in and metabolic mechanism of sheep adipose tissue development under natural grazing, thus providing valuable insights into improving the edible quality of sheep meat and developing the mutton sheep industry.

Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review.

State-of-the-art innovations in optical cardiac electrophysiology are significantly enhancing cardiac research. A potential leap into patient care is now on the horizon. Optical mapping, using fluorescent probes and high-speed cameras, offers detailed insights into cardiac activity and arrhythmias by analysing electrical signals, calcium dynamics, and metabolism. Optogenetics utilizes light-sensitive ion channels and pumps to realize contactless, cell-selective cardiac actuation for modelling arrhythmia, restoring sinus rhythm, and probing complex cell-cell interactions. The merging of optogenetics and optical mapping techniques for 'all-optical' electrophysiology marks a significant step forward. This combination allows for the contactless actuation and sensing of cardiac electrophysiology, offering unprecedented spatial-temporal resolution and control. Recent studies have performed all-optical imaging ex vivo and achieved reliable optogenetic pacing in vivo, narrowing the gap for clinical use. Progress in optical electrophysiology continues at pace. Advances in motion tracking methods are removing the necessity of motion uncoupling, a key limitation of optical mapping. Innovations in optoelectronics, including miniaturized, biocompatible illumination and circuitry, are enabling the creation of implantable cardiac pacemakers and defibrillators with optoelectrical closed-loop systems. Computational modelling and machine learning are emerging as pivotal tools in enhancing optical techniques, offering new avenues for analysing complex data and optimizing therapeutic strategies. However, key challenges remain including opsin delivery, real-time data processing, longevity, and chronic effects of optoelectronic devices. This review provides a comprehensive overview of recent advances in optical mapping and optogenetics and outlines the promising future of optics in reshaping cardiac electrophysiology and therapeutic strategies.

Impact of Obesity on Atrial Fibrillation Pathogenesis and Treatment Options.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF increases the risk of stroke, heart failure, dementia, and hospitalization. Obesity significantly increases AF risk, both directly and indirectly, through related conditions, like hypertension, diabetes, and heart failure. Obesity-driven structural and electrical remodeling contribute to AF via several reported mechanisms, including adiposity, inflammation, fibrosis, oxidative stress, ion channel alterations, and autonomic dysfunction. In particular, expanding epicardial adipose tissue during obesity has been suggested as a key driver of AF via paracrine signaling and direct infiltration. Weight loss has been shown to reverse these changes and reduce AF risk and recurrence after ablation. However, studies on how obesity affects pharmacologic or interventional AF treatments are limited. In this review, we discuss mechanisms by which obesity mediates AF and treatment outcomes, aiming to provide insight into obesity-drug interactions and guide personalized treatment for this patient subgroup.

Five Tibetan patent medicines orally for ischemic stroke: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Tibetan Patent Medicines (TPMs) have unique advantages in the treatment of ischemic stroke (IS) with the features of multi-component, multi-channel, and multi-target. In China, five TPMs mainly consisting of precious medicinal materials such as gold, pearls, and agate are widely utilized to treat IS and have achieved good results according to the current clinical practice. AIM OF THE STUDY: To systematically evaluate the efficacy and safety of the five TPMs orally in treating IS and provide a reference for future clinical application and research. MATERIALS AND METHODS: We searched the following 24 databases up to December 11, 2022: China National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database, Chinese Biomedical Database (CBM), PubMed, Embase, Web of Science, MEDLINE, Scopus, the Cochrane Library, ScienceDirect, etc. Comprehensive searches for randomized controlled trials (RCTs) of the five TPMs for IS were conducted. Outcome measures included clinical effective rate, neurological impairment score, activities of daily living (ADL), hematologic indices, and adverse events (AEs). The meta-regression, subgroup analyses, and sensitivity analyses were conducted to explore the sources of heterogeneity. We assessed the evidence grade of outcomes via the GRADE system. TSA software was used for trial sequential analyses of the clinical effective rate, neurological impairment score, and ADL. RESULTS: 17 RCTs (1603 patients) met our criteria. Compared with the control groups, the five TPMs showed greater improvement in clinical effective rate (RR = 1.23, 95% CI 1.17 to 1.29, P < 0.00001), neurological impairment score (SMD = -1.71, 95% CI -2.31 to -1.10, P < 0.00001), ADL (SMD = 1.97, 95% CI 1.26 to 2.68, P < 0.00001), hematocrit (MD = -1.56, 95% CI -2.83 to -0.29, P = 0.02), and hypersensitive-c-reactive-protein (MD = -2.96, 95% CI -3.30 to -2.61, P < 0.00001). AEs were reported in four RCTs and there was no statistical difference between groups (RD = -0.00, 95% CI -0.04 to 0.03, P = 0.82). The quality of evidence of the outcomes was rated as low to very low according to the GRADE system. The results of TSA provided firm evidence for the significant effect of the five TPMs on clinical effective rate, neurological impairment score, and ADL. CONCLUSIONS: This review showed that the five TPMs were beneficial in improving clinical effective rate, neurological impairment scores, and ADL. However, no definite conclusions for hematologic indices and AEs were drawn due to insufficient studies. Further high-quality clinical trials are required to confirm these findings.

Characterization of Type I and Type III Collagen in the Intramuscular Connective Tissue of Wuzhumuqin Sheep.

Intramuscular connective tissue (IMCT) collagen is an important factor in meat quality. This study analyzed the characteristics of type I and III collagen in the IMCT of the semitendinosus (SD) and longissimus dorsi (LD) of Wuzhumuqin sheep at different growth stages (6, 9, 12, and 18 months). Utilizing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared spectroscopy (FTIR), collagen types I and III were successfully isolated and shown to contain an intact triple helix structure. Immunofluorescence revealed that these collagens were located in the endomysium and perimysium. Collagen-related genes were significantly expressed in sheep aged 9 and 12 months. The amino acid content increased with age in type I collagen whereas it decreased in type III collagen. Furthermore, type III collagen contained more hydroxyproline (Hyd) than type I collagen. Differential scanning calorimetry (DSC) revealed that the thermal stability of collagen increased with age, accompanied by a decrease in solubility. Semitendinosus muscle had more collagen cross-linkages than LD muscle due to the high pyridinoline (Pyr) content in the endomysium. Finally, a correlation analysis highlighted the multiple correlations between characteristics in different types of collagen during sheep growth. In summary, the collagen characteristics in the IMCT of sheep were impacted by collagen type, muscle type, and age. Furthermore, the various correlations between these characteristics may play an important role in the development of IMCT.

A prediction model of atrial fibrillation recurrence after first catheter ablation by a nomogram: HASBLP score.

Background: At present, catheter ablation is an effective method for rhythm control in patients with atrial fibrillation (AF). However, AF recurrence is an inevitable problem after catheter ablation. To identify patients who are prone to relapse, we developed a predictive model that allows clinicians to closely monitor these patients and treat them with different personalized treatment plans. Materials and methods: A total of 1,065 patients who underwent AF catheter ablation between January 2015 and December 2018 were consecutively included in this study, which examines the results of a 2-year follow-up. Patients with AF were divided into development cohort and validation cohort. Univariate and multivariate analyses were carried out on the potential risk factors. Specific risk factors were used to draw the nomogram according to the above results. Finally, we verified the performance of our model compared with CHADS2 and CHA2DS2-Vasc scores by receiver operating characteristic (ROC) curve and calibration curve and plotted the decision analysis curve (DAC). Results: A total of 316 patients experienced AF recurrence. After univariate and multivariate analyses, AF history (H), age (A), snoring (S), body mass index (BMI) (B), anteroposterior diameter of left atrial (LA) (L), and persistent AF (P) were included in our prediction model. Our model showed a better performance compared with CHADS2 and CHA2DS2-Vasc scores, and the area under ROC curve (95%CI) was 0.7668 (0.7298-0.8037) vs. 0.6225 (0.5783-0.6666) and 0.6267 (0.5836-0.6717). Conclusion: We established a nomogram (HASBLP score) for predicting AF recurrence after the first catheter ablation at a 2-year follow-up, which can be used as a tool to guide future follow-up of patients. However, its usefulness needs further validation.

The role of alcohol consumption on echocardiographic and electrophysiologic changes in atrial fibrillation.

BACKGROUND: A wealth of evidence suggests that alcohol consumption is a risk factor for atrial fibrillation (AF); however, the mechanisms underlying this association are unclear. This makes it challenging to develop therapeutic strategies in patients with AF attributed to alcohol consumption. PURPOSE: To investigate the echocardiographic and electrophysiologic changes caused by alcohol consumption in patients with AF. METHODS: The study was registered in Chinese Clinical Trial Registry (Registration number ChiCTR2000041575). Data on 134 consecutive non-valvular AF patients who underwent radiofrequency catheter ablation in our center was collected from April 1, 2019 to June 30, 2020. Patients were divided into no-alcohol (72) and alcohol groups [categorized into light (34), moderate (11) and heavy (17) alcohol consumption]. All patients underwent echocardiographic and electrophysiologic examinations for the assessment of left atrial (LA) strain, inter-atrial conduction, intra-atrial conduction, and atrial effective refractory period (ERP). RESULTS: Overall, the mean age was 61 ± 11 years and 87 (65%) were males. Compared with the no-alcohol group, impaired peak LA longitudinal strain, obvious inter-atrial conduction delay and increasing ERP dispersion were observed in the alcohol group. Intra-atrial conduction delay and ERP dispersion increased with increasing amounts of alcohol consumption. CONCLUSION: Alcohol consumption was associated with substantial abnormal echocardiographic and electrophysiologic changes in AF patients. These changes may contribute to the occurrence and progression of AF attributed to alcohol consumption, which may help in the development of new strategies for the prevention and management of AF. However further investigation is required.

Case Report: A Rare Case of Severe Coronary Venous Spasm During Radiofrequency Ablation of Premature Ventricular Contraction.

Coronary venous spasm has never been reported during premature ventricular extrasystole ablation. We report a 20-year-old female patient who experienced a severe spasm of the great cardiac vein during radiofrequency ablation for premature ventricular contractions, which were relieved eventually by the administration of intracoronary nitroglycerine. The operation was successfully completed, leading to a long-term resolution of her palpitation symptoms.

Effectiveness and safety of Ginkgo biloba extract (GBE50) in the treatment of dizziness caused by cerebral arteriosclerosis: a multi-center, double-blind, randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of Ginkgo biloba extract (GBE50) in the treatment of dizziness caused by cerebral arteriosclerosis. METHODS: This was a multi-center, double-blind, double-dummy, positive-controlled, parallel randomized controlled clinical trial with 1? allocation. We recruited 404 patients with dizziness caused by cerebral arteriosclerosis (blood stasis symptom pattern) in 10 hospitals in China. GBE50 group received GBE50 and Naoxinqing tablet (NXQ) of mimetic agent, control group received NXQ and GBE50 of mimetic agent. The main outcome was Traditional Chinese Medicine (TCM) symptom pattern score of blood stasis after 6 weeks. The secondary outcomes were changes in the dizziness handicap inventory (DHI) score, vertigo visual analogue scale (VAS) score, the university of California vertigo questionnaire (UCLA-DQ) score and single-item symptom score of TCM from baseline to 2, 4 and 6 weeks. Safety indicators included the incidence of adverse events, severe adverse events and laboratory examination including blood routine, liver function, renal function, and so forth. RESULTS: The total effective rate of TCM symptom pattern score in the GBE50 group after 6 weeks of treatment was higher than that in the control group, the difference in rate was statistically significant (92.67% vs 83.07%, P = 0.004). Compared with the control group, there was no difference in the incidence of adverse reactions (9.95% vs 14.85%, P = 0.136). CONCLUSION: The treatment of dizziness caused by cerebral arteriosclerosis with GBE50 is effective, safe and reliable.

Is Epicardial Adipose Tissue Associated with Atrial Fibrillation Following Cardiac Surgery? A Systematic Review and Meta-Analysis.

BACKGROUND: Although epicardial adipose tissue (EAT) has been proven to be related to atrial fibrillation (AF) and post-ablation AF recurrence, the association between EAT and AF after cardiac surgery (AFACS) remains unclear. OBJECTIVE: This study was a systematic review and meta-analysis that assessed the relationship between EAT and AFACS. METHODS: Electronic databases were systematically searched for "atrial fibrillation" and "epicardial adipose tissue." The analysis was stratified according to the EAT measurement into three meta-analyses as (1) total EAT volume, (2) left atrial (LA)-EAT volume, and (3) EAT thickness. Standardized mean difference (SMD) was estimated using a random effects model. RESULTS: Eight articles with 10 studies (546 patients) were included. The meta-analysis revealed that EAT was higher in those with AFACS irrespective of the EAT measurement (total EAT volume: SMD = 0.56 mL, 95% confidence interval, CI = 0.56-1.10 mL, I2 = 0.90, P = .04; EAT thickness: SMD = 0.85 mm, 95% CI = 0.04-1.65 mm, I2 = 0.90, P = .04; LA-EAT volume: SMD = 0.57 mL, 95% CI = 0.23-0.92 mL, I2 = 0.00, P = .001). CONCLUSION: EAT was higher in patients with AFACS, measured either as volume or thickness.

Feasibility and safety of left atrial appendage occlusion guided by procedural fluoroscopy only: A pilot study.

BACKGROUND: Left atrial appendage occlusion (LAAO) is usually performed via the guidance of procedural transesophageal echocardiography (TEE) companied by general anesthesia (GA). OBJECTIVE: To investigate the feasibility and safety of LAAO guided by procedural fluoroscopy only. METHODS: The patients eligible for LAAO were enrolled into the current study and received implantation of either Watchman device or LAmbre device. The procedure was carried out with procedural fluoroscopy only and no companied GA; the position, shape, and leakage of the device were assessed by contrast angiography. TEE was performed after 3-month follow-up to evaluate the thrombosis, and leakage of device. RESULTS: Ninety-seven patients with atrial fibrillation (AF) with either Watchman device (n = 49) or LAmbre device (n = 48) were consecutively enrolled. Watchman device group was of lower CHA2 DS2 -VASc and HAS-BLED scores compared with LAmbre device groups (p < .05); the two groups had similar distributions of other baseline characteristics (p > .05), including procedural success rate (98.0% vs. 97.9%), mean procedure time, mean fluoroscopy time, total radiation dose, contrast medium dose, percentage of peri-device leakage. Pericardial effusions requiring intervention occurred in two of the Watchman group. TEE follow-up found no patient with residual leakage ≥5 mm at 3 months and no device related thrombosis (DRT). During the 22.0 ± 11.1 months follow-up, two patients experienced ischemic stroke. CONCLUSIONS: LAAO with the procedural imaging of fluoroscopy only exhibited the promising results of efficacy and safety. A prospective randomized multicenter study would be required to verify the observations in this study.

Multiple potential roles of thymosin ß4 in the growth and development of hair follicles.

The hair follicle (HF) is an important mini-organ of the skin, composed of many types of cells. Dermal papilla cells are important signalling components that guide the proliferation, upward migration and differentiation of HF stem cell progenitor cells to form other types of HF cells. Thymosin ß4 (Tß4), a major actin-sequestering protein, is involved in various cellular responses and has recently been shown to play key roles in HF growth and development. Endogenous Tß4 can activate the mouse HF cycle transition and affect HF growth and development by promoting the migration and differentiation of HF stem cells and their progeny. In addition, exogenous Tß4 increases the rate of hair growth in mice and promotes cashmere production by increasing the number of secondary HFs (hair follicles) in cashmere goats. However, the molecular mechanisms through which Tß4 promotes HF growth and development have rarely been reported. Herein, we review the functions and mechanisms of Tß4 in HF growth and development and describe the endogenous and exogenous actions of Tß4 in HFs to provide insights into the roles of Tß4 in HF growth and development.

Thromboembolic Risk of Cessation of Oral Anticoagulation Post Catheter Ablation in Patients With and Without Atrial Fibrillation Recurrence.

Cessation of oral anticoagulation (OAC) is common after the first 3 months of catheter ablation of atrial fibrillation (AF); however, thromboembolic risk has not been defined in patients with and without AF recurrence (RAF vs NRAF) post ablation. We identified 796 patients who discontinued OAC at 3 months post AF ablation from January 2015 to May 2018 in our center. Regular follow-up was performed to detect RAF, collect medication management and thromboembolic and major bleeding events. CHA2DS2-VASc score was 1.79 ± 1.50; 547 (68.7%) patients were at intermediate and high risk (i.e., CHA2DS2-VASc score ≥1 in male patients, or ≥2 in female patients); 169 (21.2%) were RAF. During 29.2±12.2 months follow-up, the incidence rate of thromboembolism was 1.62 per 100 patient-year (7 in 431 years) in RAF, 0.33 per 100 patient-year (5 in 1,503 years) in NRAF. After adjusting for potential confounding factors, RAF was associated with more 3.5-fold higher rate of thromboembolism compared with NRAF (adjusting HR, 4.488; 95% CI, 1.381 to 14.586). Rate of thromboembolism was even higher in patients with intermediate and high risk (2.16 per 100 patient-year [7 in 323 years] vs 0.38 per 100 patient-year [4 in 1,043 years], aHR, 5.807; 95% CI, 1.631 to 20.671). In multivariate logistic regression analysis, RAF was the only independent predictor of thromboembolism (4.837 [1.498 to 15.621], p = 0.008). In conclusion, cessation of OAC in NRAF may be reasonable, especially for patients with the contraindications for continuing OAC; however, cessation of OAC appeared unsafe in RAF with a high-risk stroke profile because of high incidence rate of thromboembolism.

Cx43 promotes SHF-DPCs proliferation in the hair follicle of Albas cashmere goats from anagen to telogen.

Connexin 43 (Cx43), known to form gap junction transmembrane channels between the cytoplasm of two adjacent cells, plays a key role in physiological functions, such as regulating cell growth, differentiation, and maintaining tissue homeostasis. Cashmere goat is an important farm animal that provides cashmere, which was produced by secondary hair follicles (SHF), for human consumption; however, there is no report about the role of Cx43 on the growth and development of SHF in cashmere goat. In this study, we investigated the effect of Cx43 on proliferation secondary hair follicle dermal papilla cells (SHF-DPCs) in Albas cashmere goat. In SHF-DPCs, Cx43 overexpression promoted cell proliferation and upregulated the expression of IGF-1, whereas Cx43 knockdown was associated with the opposite effects. These results suggested that Cx43 may promote cell proliferation by inducing IGF-1. Overall, our research not only contributes to a better understanding of the mechanism of the growth and development of SHF in cashmere goat, but also shed light on cashmere quality control in the future.

Wt1 deficiency causes undifferentiated spermatogonia accumulation and meiotic progression disruption in neonatal mice.

Spermatogenesis is a complex process involving the regulation of multiple cell types. As the only somatic cell type in the seminiferous tubules, Sertoli cells are essential for spermatogenesis throughout the spermatogenic cycle. The Wilms tumor gene, Wt1, is specifically expressed in the Sertoli cells of the mouse testes. In this study, we demonstrated that Wt1 is required for germ cell differentiation in the developing mouse testes. At 10 days post partum, Wt1-deficient testes exhibited clear meiotic arrest and undifferentiated spermatogonia accumulation in the seminiferous tubules. In addition, the expression of claudin11, a marker and indispensable component of Sertoli cell integrity, was impaired in Wt1(-/flox); Cre-ER(TM) testes. This observation was confirmed in in vitro testis cultures. However, the basal membrane of the seminiferous tubules in Wt1-deficient testes was not affected. Based on these findings, we propose that Sertoli cells' status is affected in Wt1-deficient mice, resulting in spermatogenesis failure.

Molecular basis of the internalization of bovine immunodeficiency virus Tat protein.

Bovine Immunodeficiency Virus (BIV) is a nonacute, pathogenic, and horizontally transmitted lentivirus. It shares the parallel properties in morphology and genetics with human immunodeficiency virus type 1 and other lentiviruses. BIV encodes its own transactivator (BTat), which transactivates its cognate long terminal repeat (LTR). However, the mechanism involved in the transactivation is different from that in HIV and other lentiviruses. We determined the mechanisms of BTat internalization by cells and the effect of BTat on neighboring cells. The green fluorescent protein fusion analysis indicated that the internalization of extracellular BTat was a time and dose-dependent, but endocytosis and energy-independent manner. Arginine residues in the arginine-rich motif (ARM) of BTat were definitively responsible for the internalization. Internalized BTat is predominantly present in the nucleus, resulting in LTR activation and NF-kappaB induction. These results propose that the secretion and internalization of BTat facilitates BIV in influencing neighboring cells and makes the cellular environment propitious to viral replication.

Internalization of Jembrana disease virus Tat: possible pathway and implication.

Jembrana disease virus (JDV) is a lentivirus highly related to the bovine immunodeficiency virus (BIV). It causes an acute disease with high mortality rate within 1-2 weeks. JDV encodes the most potent Tat (JTat) of any of the lentiviruses. JTat can transactivate all LTRs and functionally substitute for HIV Tat in the viral genome and may function as a pivotal regulator in the acute pathogenesis of JDV. The goal of this paper is to study JTat internalization by cells, the mechanisms involved in internalization, and the effect of JTat on neighbouring cells. By quantification and fluorescence microscopy, we found that the internalization of extracellular EGFP-JTat fusion protein was both time and dose-dependent, but endocytosis and energy independent. We identified that arginines which were responsible for the internalization. Internalized JTat was distributed in both the nucleus and the cytoplasm, could transactivate JDV LTR and modulate cellular gene expression. Based on our findings, we propose that secretion and internalization of JTat may be a way for JDV to influence neighbouring cells and make the cellular environment more amenable to viral infection.