Assessing parameter efficient methods for pre-trained language model in annotating scRNA-seq data.

Annotating cell types of single-cell RNA sequencing (scRNA-seq) data is crucial for studying cellular heterogeneity in the tumor microenvironment. Recently, large-scale pre-trained language models (PLMs) have achieved significant progress in cell-type annotation of scRNA-seq data. This approach effectively addresses previous methods' shortcomings in performance and generalization. However, fine-tuning PLMs for different downstream tasks demands considerable computational resources, rendering it impractical. Hence, a new research branch introduces parameter-efficient fine-tuning (PEFT). This involves optimizing a few parameters while leaving the majority unchanged, leading to substantial reductions in computational expenses. Here, we utilize scBERT, a large-scale pre-trained model, to explore the capabilities of three PEFT methods in scRNA-seq cell type annotation. Extensive benchmark studies across several datasets demonstrate the superior applicability of PEFT methods. Furthermore, downstream analysis using models obtained through PEFT showcases their utility in novel cell type discovery and model interpretability for potential marker genes. Our findings underscore the considerable potential of PEFT in PLM-based cell type annotation, presenting novel perspectives for the analysis of scRNA-seq data.

Potential mechanism of probiotic fermentation of Auricularia cornea var. Li./blueberry to reduce obesity induced by a high-fat diet.

The primary objective of this research was to investigate the effects of fermented Auricularia cornea var. Li./blueberry (FACB) on the gut microbiota of these super-large mouse models. The study, found that the groups who were given different amounts of FACB saw a significant reduction in their triglyceride and total cholesterol levels. There was a noteworthy increase in the ranks of high-density lipoprotein cholesterol (HDL-C) (P < 0.05). Furthermore, it was noted that FACB influenced the gut microbiota of the obese rats, improving in both the variety and quantity of short-chain fatty acids present in their intestines. This research provided the inaugural evidence of FACB's potential as an effective anti-obesity agent in a high-fat diet model, implying it could serve as a preventive measure against obesity.

Selenium Nanoparticles Attenuate Cobalt Nanoparticle-Induced Skeletal Muscle Injury: A Study Based on Myoblasts and Zebrafish.

Cobalt alloys have numerous applications, especially as critical components in orthopedic biomedical implants. However, recent investigations have revealed potential hazards associated with the release of nanoparticles from cobalt-based implants during implantation. This can lead to their accumulation and migration within the body, resulting in adverse reactions such as organ toxicity. Despite being a primary interface for cobalt nanoparticle (CoNP) exposure, skeletal muscle lacks comprehensive long-term impact studies. This study evaluated whether selenium nanoparticles (SeNPs) could mitigate CoNP toxicity in muscle cells and zebrafish models. CoNPs dose-dependently reduced C2C12 viability while elevating reactive oxygen species (ROS) and apoptosis. However, low-dose SeNPs attenuated these adverse effects. CoNPs downregulated myogenic genes and α-smooth muscle actin (α-SMA) expression in C2C12 cells; this effect was attenuated by SeNP cotreatment. Zebrafish studies confirmed CoNP toxicity, as it decreased locomotor performance while inducing muscle injury, ROS generation, malformations, and mortality. However, SeNPs alleviated these detrimental effects. Overall, SeNPs mitigated CoNP-mediated cytotoxicity in muscle cells and tissue through antioxidative and antiapoptotic mechanisms. This suggests that SeNP-coated implants could be developed to eliminate cobalt nanoparticle toxicity and enhance the safety of metallic implants.

Influence of Auricularia cornea Polysaccharide Coating on the Stability and Antioxidant Activity of Liposomes Ginsenoside Rh2.

Liposomes (Lip) are microstructures containing lipid and aqueous phases for encapsulation and delivery of bioactivators. In this study, Ginsenoside Rh2 liposomes (Rh2-Lip) were prepared by a thin-film hydrated ultrasonic binding method. But they are not stable during storage. In addition, Rh2-Lip was wrapped with Auricultural cornea polysaccharide (ACP) and Chitosan (CS) as coating materials to improve stability. CS coating was used as a positive control. The particle sizes determined by dynamic light scattering (DLS) showed 183 ± 5.52 nm for liposomes, 197 ± 6.7 nm for Auricultural cornea polysaccharide coated liposomes (ACP-Rh2-Lip), and 198 ± 3.5 nm for Chitosan coated liposomes (CS-Rh2-Lip). The polydispersity index (PDI) of all liposomes was less than 0.3. Transmission electron microscopy (TEM) showed that ACP and CS were successfully encapsulated on the liposome surface. In vitro simulations of digestive stability in the gastrointestinal tract showed that ACP-Rh2-Lip and CS-Rh2-Lip were more stable in gastrointestinal fluids compared to Lip. The antioxidant experiment revealed that ACP-Rh2-Lip has greater antioxidant activity than Lip. The purpose of this study was to look into the effects of ACP-Rh2-Lip and to offer a reference for Ginsenoside Rh2 (Rh2) delivery.

Phosphorylated heat shock protein 27 improves the bone formation ability of osteoblasts and bone marrow stem cells from patients with adolescent idiopathic scoliosis.

Background: Adolescent idiopathic scoliosis (AIS) is a scoliotic deformity of unknown etiology that occurs during adolescent development. Abnormal bone metabolism is closely related to AIS, but the cause is uncertain. Recent studies have shown that heat shock protein 27 (HSP27) and its phosphorylation (pHSP27) play important roles in bone metabolism. However, whether HSP27 and pHSP27 are involved in abnormal bone metabolism in AIS is unclear. Methods: Osteoblasts (OBs) and bone marrow stem cells (BMSCs) were extracted from the facet joints and bone marrow of AIS patients and controls who underwent posterior spinal fusion surgery. The expression levels of HSP27 and pHSP27, as well as the expression levels of bone formation markers in OBs from AIS patients and controls, were examined by quantitative real-time PCR (qRT-PCR) and Western blotting. The mineralization ability of OBs from AIS patients and controls was analyzed by alizarin red staining after osteogenic differentiation. Heat shock and thiolutin were used to increase the levels of pHSP27 in OBs, and the levels of bone formation markers were also investigated. In addition, the levels of pHSP27 and the bone formation ability of BMSCs from AIS patients and controls were investigated after heat shock treatment. Results: Lower pHSP27 levels and impaired osteogenic differentiation abilities were observed in the OBs of AIS patients than in those of controls. Thiolutin increased HSP27 phosphorylation and increased the mRNA levels of SPP1 and ALPL in OBs from AIS patients. Heat shock treatment increased SPP1 and HSP27 mRNA expression, pHSP27 levels, OCN expression, and mineralization ability of both OBs and BMSCs from AIS patients. Conclusion: Heat shock treatment and thiolutin can increase the levels of pHSP27 and further promote the bone formation of OBs and BMSCs from AIS patients. Therefore, decreased pHSP27 levels may be associated with abnormal bone metabolism in AIS patients.

BMP6 participates in the pathogenesis of adolescent idiopathic scoliosis by regulating osteopenia.

Adolescent idiopathic scoliosis (AIS) is a complex disease characterized by three-dimensional structural deformities of the spine. Its pathogenesis is associated with osteopenia. Bone-marrow-derived mesenchymal stem cells (BMSCs) play an important role in bone metabolism. We detected 1919 differentially expressed mRNAs and 744 differentially expressed lncRNAs in BMSCs from seven patients with AIS and five patients without AIS via high-throughput sequencing. Multiple analyses identified bone morphogenetic protein-6 (BMP6) as a hub gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS. BMP6 expression was found to be decreased in AIS and its knockdown in human BMSCs significantly altered the degree of osteogenic differentiation. Additionally, CAP1-217 has been shown to be a potential upstream regulatory molecule of BMP6. We showed that CAP1-217 knockdown downregulated the expression of BMP6 and the osteogenic differentiation of BMSCs. Simultaneously, knockout of BMP6 in zebrafish embryos significantly increased the deformity rate. The findings of this study suggest that BMP6 is a key gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS via the CAP1-217/BMP6/RUNX2 axis.

Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway.

BACKGROUND: Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. METHODS: We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. RESULTS: DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. CONCLUSIONS: Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.

Effects of lifestyle intervention on adults with metabolic associated fatty liver disease: A systematic review and meta-analysis.

Introduction: This systematic review and meta-analysis evaluates the overall effects of lifestyle interventions upon hepatic fat content and metabolism-related indicators among adults with metabolic associated fatty liver disease. Methods: It was registered under PROSPERO (CRD42021251527). We searched PubMed, EMBASE, MEDLINE, Cochrane, CINAHL, Scopus, CNKI, Wan-fang, VIP, and CBM from the inception of each database to May 2021 for RCT studies of lifestyle interventions on hepatic fat content and metabolism-related indicators. We used Review Manager 5.3 for meta-analysis and used text and detailed tabular summaries when heterogeneity existed. Results: Thirty-four RCT studies with 2652 participants were included. All participants were obesity, 8% of whom also had diabetes, and none was lean or normal weight. Through subgroup analysis, we found low carbohydrate diet, aerobic training and resistance training significantly improved the level of HFC, TG, HDL, HbA1c, and HOMA-IR. Moreover, low carbohydrate diet is more effective in improving HFC than low fat diet and resistance training is better than aerobic training in reduction in HFC and TG (SMD, -0.25, 95% CI, -0.45 to -0.06; SMD, 0.24, 95% CI, 0.03 to 0.44, respectively). Discussion: Overall, this is the first review that systematically synthesizes studies focused on the effects of various lifestyle on adults with MAFLD. The data generated in this systematic review were more applicable to obesity MAFLD rather than lean or normal weight MAFLD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42021251527).

Low Molecular Weight Heparin Improves the Inflammatory State of Acute Sinusitis Rats Through Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway.

Introduction: Low molecular weight heparin (LMWH), a natural sulfated glycosaminoglycan with an affinity for proangiogenic factors, is produced by chemical or enzymatic depolymerization of unfractionated heparin (UFH). Known for its anticoagulant effects, LMWH has recently been reported to have a strong anti-inflammatory effect on colitis, myocarditis, and airway inflammation. However, as a newly-developed drug, its anti-inflammatory mechanism in upper respiratory tract inflammation has not been well-studied. Methods: SD rats were randomly divided into control and experimental groups. The experimental group was established by building an acute nasal sinusitis model with expansion sponges mixed with Streptococcus pneumoniae. Then the experimental group rats were subcutaneously injected with different concentrations of LMWH. After seven consecutive days of injection, some rats were sacrificed, and blood and nasal mucosa samples were taken to determine their inflammation status. The remaining acute sinusitis rats were randomly selected for a week of nasal irrigation with normal saline or saline mixed with different concentrations of LMWH. One week later, rats were sacrificed, and samples of blood and nasal mucosa were taken to determine the inflammation status. Results: Rat nasal mucosa in the model group had obvious inflammation. The degree of nasal mucosa inflammation damage in the experimental group was lower than in the experimental control group, proving that LMWH has a protective effect on the nasal mucosa and that the effect correlates with dosage. Irrigation of the nose with saline mixed with LMWH can improve the anti-inflammatory effect. Protein related to the TLR4-MyD88-NF-κB signaling pathway was activated in the acute sinusitis rat model, and LMWH can significantly inhibit its expression. Conclusion: This is the first report of the anti-inflammatory effect of LMWH in acute upper respiratory tract inflammation, together with an explanation of its anti-inflammatory mechanism. The findings contribute a theoretical basis for its potential anti-tumor effect.

Target-flanker similarity effects reflect image segmentation not perceptual grouping.

When responding to the identity of a visual target, nearby stimuli (flankers) that are associated with the same response as the target cause faster and more accurate responding than flankers that are associated with different responses. Because this flanker-congruence effect (FCE) decreases with increasing target-flanker separation, it was thought to reflect limited precision of spatial selection mechanisms. Later studies, however, showed that FCEs are larger when the target and flankers are the same color compared to when they are different colors. This led to the group selection hypothesis, which states that flankers are perceptually grouped with the target and are obligatorily selected along with it, regardless of spatial separation. An alternative hypothesis, the image segmentation hypothesis, states that feature differences facilitate the segmentation of visual information into relevant and irrelevant parts, thereby mitigating the limitations of spatial precision of selection mechanisms. We test between these hypotheses using a design in which targets and flankers are grouped or not grouped, while holding feature differences in the stimulus constant. Contrary to earlier results, we found that same-colored flankers do not yield larger FCEs than different-colored flankers when feature differences are held constant. We conclude that similarity effects on the FCE reflect differential support for image segmentation, on which selection depends, rather than the obligatory selection of perceptually grouped flankers and targets.

Genetic analysis of MC1R variants in Chinese Han patients with sporadic Parkinson's disease.

Parkinson's disease (PD, OMIM 168600) is a neurodegenerative disorder featured by degeneration of melanin-positive dopaminergic neurons. Epidemiologic studies have suggested that PD and malignant melanoma (MM) might share common genetic components. Recently, the p.R160W variant in the melanocortin 1 receptor gene (MC1R, OMIM 155555), a risk factor for MM, has been identified to be associated with PD in Spanish population. To explore whether the MC1R variants are associated with sporadic PD in Chinese population, we designed a case-control comparison study and studied three variants, including rs3212366 (p.F196L), rs33932559 (p.I120T) and rs34090186 (p.R67Q), in the MC1R gene in 512 Chinese Han patients with sporadic PD and 512 age, gender and ethnicity matched normal controls. For rs3212366, only the TT genotype was identified in both PD and control cohorts. For variants rs33932559 and rs34090186, we did not identify any statistically significant difference in either genotypic distribution or allelic distribution between the PD cohort and control cohort, and in addition, we did not identify any related haplotype that would either increase the risk for PD or play a protective role against PD. Our data suggest that none of the three variants of the MC1R gene and related haplotypes be associated with sporadic form of PD in Chinese Han population from Mainland China.