L-cysteine contributes to destructive activities of odontogenic cysts/tumor.

BACKGROUND: Odontogenic cysts/tumor can cause severe bone destruction, which affects maxillofacial function and aesthetics. Meanwhile, metabolic reprogramming is an important hallmark of diseases. Changes in metabolic flow affect all aspects of disease, especially bone-related diseases. At present, the researches on pathogenesis of odontogenic cysts/tumor are mainly focused on the level of gene regulation, but the effects of metabolic alterations on odontogenic cysts/tumor have still underexplored. MATERIALS AND METHODS: Imaging analysis was used to evaluate the lesion size of different odontogenic lesions. Tartrate resistant acid phosphatase (TRAP) and immunohistochemistry (IHC) assays were utilized to detect the differences in bone destruction activity in odontogenic cysts and tumors. Furthermore, metabolomics and weighted gene co-expression network analysis (WGCNA) were conducted for the metabolomic features and key metabolite screening, respectively. The effect of ferroptosis inhibition on bone destruction was confirmed by IHC, immunofluorescence, and malondialdehyde colorimetric assay. RESULTS: The bone destruction activity of ameloblastoma (AM) was the strongest and the weakest in odontogenic cysts (OC). High-throughput targeted metabolomics was used to map the metabolomic profiles of OC, odontogenic keratocyst (OKC) and AM. WGCNA and differential analysis identified L-cysteine in OKC and AM. Cystathionine γ-lyase (CTH) was further screened by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The functions of L-cysteine were further validated. Finally, we confirmed that CTH affected destructive activities by regulating the sensitivity of epithelial cells to ferroptosis. CONCLUSION: High-throughput targeted metabolomics performed on diseased tissue confirmed the unique alteration of metabolic profiles in OKC and AM. CTH and its metabolite L-cysteine are the key factors regulating destructive activities.

Association of preoperative frailty with the risk of postoperative delirium in older patients undergoing hip fracture surgery: a prospective cohort study.

OBJECTIVE: This study aimed to explore the correlation between preoperative frailty and the risk of postoperative delirium (POD) in older patients undergoing hip fracture surgery. METHODS: In total, 148 patients with hip fractures who were admitted to Tsinghua Changgung Hospital (Beijing, China) between January 2022 and January 2023 were involved in this study. Preoperative frailty scales were assessed, of which the CAM scale was postoperatively administered every morning and evening on days 1, 2, 3, 5, and 7. Binary logistic regression analysis was conducted to determine the correlation between preoperative frailty and the risk of POD. RESULTS: Among 148 older patients with hip fractures, 71 (48.0%) were identified as preoperative frail and 77 (52.0%) as non-frail. The overall incidence of POD on day 7 was 24.3% (36/148), and preoperative frailty was associated with a significantly higher risk of POD compared with non-frailty (42.3% vs. 7.8%, P < 0.001). The binary logistic regression analysis revealed that preoperative frailty was noted as an independent risk factor for the risk of POD in older patients undergoing hip fracture surgery (P = 0.002). CONCLUSION: Preoperative frailty increased the risk of POD in older patients undergoing hip fracture surgery. DISCUSSION: Preoperative assessment of frailty in geriatric hip surgery can timely identify potential risks and provide interventions targeting frailty factors to reduce the incidence of POD in older patients undergoing hip fracture surgery. The findings suggested that preoperative frailty could increase the risk of POD in older patients undergoing hip fracture surgery. Further research is necessary to determine whether perioperative interventions aimed at enhancing frailty can mitigate the risk of POD and improve prognosis in older patients undergoing hip fracture surgery.

Recent Advances in Synthesis of Non-Alternating Polyketone Generated by Copolymerization of Carbon Monoxide and Ethylene.

The copolymers of carbon monoxide (CO) and ethylene, namely aliphatic polyketones (PKs), have attracted considerable attention due to their unique property and degradation. Based on the arrangement of the ethylene and carbonyl groups in the polymer chain, PKs can be divided into perfect alternating and non-perfect alternating copolymers. Perfect alternating PKs have been previously reviewed, we herein focus on recent advances in the synthesis of PKs without a perfect alternating structure including non-perfect alternating PKs and PE with in-chain ketones. The chain structure of PKs, catalytic copolymerization mechanism, and non-alternating polymerization catalysts including phosphine-sulfonate Pd, diphosphazane monoxide (PNPO) Pd/Ni, and phosphinophenolate Ni catalysts are comprehensively summarized. This review aims to enlighten the design of ethylene/CO non-alternating polymerization catalysts for the development of new polyketone materials.

Microstate feature fusion for distinguishing AD from MCI.

Electroencephalogram (EEG) microstates provide powerful tools for identifying EEG features due to their rich temporal information. In this study, we tested whether microstates can measure the severity of Alzheimer's disease (AD) and mild cognitive impairment (MCI) in patients and effectively distinguish AD from MCI. We defined two features using transition probabilities (TPs), and one was used to evaluate between-group differences in microstate parameters to assess the within-group consistency of TPs and MMSE scores. Another feature was used to distinguish AD from MCI in machine learning models. Tests showed that there were between-group differences in the temporal characteristics of microstates, and some kinds of TPs were significantly correlated with MMSE scores within groups. Based on our newly defined time-factor transition probabilities (TTPs) feature and partial accumulation strategy, we obtained promising scores for accuracy, sensitivity, and specificity of 0.938, 0.923, and 0.947, respectively. These results provide evidence for microstates as a neurobiological marker of AD.

Glycometabolic reprogramming-mediated proangiogenic phenotype enhancement of cancer-associated fibroblasts in oral squamous cell carcinoma: role of PGC-1α/PFKFB3 axis.

BACKGROUND: Angiogenesis is a key rate-limiting step in the process of tumour progression. Cancer-associated fibroblasts (CAFs), the most abundant component OSCC stroma, play important roles in pro-angiogenesis. Recently, the stroma "reverse Warburg effect" was proposed, and PFKFB3 has been brought to the forefront as a metabolic enzyme regulating glycometabolism. However, it remains unclear whether glycometabolism reprogramming is involved in promoting the angiogenesis of CAFs. METHODS: CAFs and paracancerous fibroblasts (PFs) were isolated from OSCC and adjacent tissues. We detected the pro-angiogenesis and glycometabolism phenotype of three pairs of fibroblasts. Targeted blockage of PFKFB3 or activation of PGC-1α signal was used to investigate the effect of glycolysis on regulating angiogenesis of CAFs in vitro and vivo. RESULTS: CAFs exhibited metabolic reprogramming and enhanced proangiogenic phenotype compared with PFs. Inhibition of PFKFB3-dependent glycolysis impaired proangiogenic factors (VEGF-A, PDGF-C and MMP9) expression in CAFs. Furthermore, CAFs proangiogenic phenotype was regulated by glycometabolism through the PGC-1α/PFKFB3 axis. Consistently, PGC-1α overexpression or PFKFB3 knockdown in CAFs slowed down tumour development by reducing tumour angiogenesis in the xenograft model. CONCLUSION: CAFs of OSCC are characterised with glycometabolic reprogramming and enhanced proangiogenic phenotypes. Our findings suggest that activating PGC-1α signalling impairs proangiogenic phenotype of CAFs by blocking PFKFB3-driven glycolysis.

Adaptive Evolution of the Fox Coronavirus Based on Genome-Wide Sequence Analysis.

Purpose: To report the first complete fox coronavirus (CoV) genome sequence obtained through genome-wide amplifications and to understand the adaptive evolution of fox CoV. Methods: Anal swab samples were collected from 35 foxes to detect the presence of CoV and obtain the virus sequence. Phylogenetic analysis was conducted using MrBayes. The possibility of recombination within these sequences was assessed using GARD. Analysis of the levels of selection pressure experienced by these sequences was assessed using methods on both the PAML and Data Monkey platforms. Results: Of the 35 samples, two were positive, and complete genome sequences for the viruses were obtained. Phylogenetic analysis, using Bayesian methods, of these sequences, together with other CoV sequences, revealed that the fox CoV sequences clustered with canine coronavirus (CCoV) sequences, with sequences from other carnivores more distantly related. In contrast to the feline, ferret and mink CoV sequences that clustered into species-specific clades, the fox CoV fell within the CCoV clade. Minimal evidence for recombination was found among the sequences. A total of 7, 3, 14, and 2 positively selected sites were identified in the M, N, S, and 7B genes, respectively, with 99, 111, and 581 negatively selected sites identified in M, N, and S genes, respectively. Conclusion: The complete genome sequence of fox CoV has been obtained for the first time. The results suggest that the genome sequence of fox CoV may have experienced adaptive evolution in the genes replication, entry, and virulence. The number of sites in each gene that experienced negative selection is far greater than the number that underwent positive selection, suggesting that most of the sequence is highly conserved and important for viral survive. However, positive selection at a few sites likely aided these viruses to adapt to new environments.

Whole Genome Sequencing Reveals Signatures for Artificial Selection for Different Sizes in Japanese Primitive Dog Breeds.

Body size is an important trait in companion animals. Recently, a primitive Japanese dog breed, the Shiba Inu, has experienced artificial selection for smaller body size, resulting in the "Mame Shiba Inu" breed. To identify loci and genes that might explain the difference in the body size of these Shiba Inu dogs, we applied whole genome sequencing of pooled samples (pool-seq) on both Shiba Inu and Mame Shiba Inu. We identified a total of 13,618,261 unique SNPs in the genomes of these two breeds of dog. Using selective sweep approaches, including F ST, H p and XP-CLR with sliding windows, we identified a total of 12 genomic windows that show signatures of selection that overlap with nine genes (PRDM16, ZNF382, ZNF461, ERGIC2, ENSCAFG00000033351, CCDC61, ALDH3A2, ENSCAFG00000011141, and ENSCAFG00000018533). These results provide candidate genes and specific sites that might be associated with body size in dogs. Some of these genes are associated with body size in other mammals, but 8 of the 9 genes are novel candidate genes that need further study.

Pooled Sequencing Analysis of Geese (Anser cygnoides) Reveals Genomic Variations Associated With Feather Color.

During the domestication of the goose a change in its feather color took place, however, the molecular mechanisms responsible for this change are not completely understood. Here, we performed whole-genome resequencing on three pooled samples of geese (feral and domestic geese), with two distinct feather colors, to identify genes that might regulate feather color. We identified around 8 million SNPs within each of the three pools and validated allele frequencies for a subset of these SNPs using PCR and Sanger sequencing. Several genomic regions with signatures of differential selection were found when we compared the gray and white feather color populations using the F ST and Hp approaches. When we combined previous functional studies with our genomic analyses we identified 26 genes (KITLG, MITF, TYRO3, KIT, AP3B1, SMARCA2, ROR2, CSNK1G3, CCDC112, VAMP7, SLC16A2, LOC106047519, RLIM, KIAA2022, ST8SIA4, LOC106044163, TRPM6, TICAM2, LOC106038556, LOC106038575, LOC106038574, LOC106038594, LOC106038573, LOC106038604, LOC106047489, and LOC106047492) that potentially regulate feather color in geese. These results substantially expand the catalog of potential feather color regulators in geese and provide a basis for further studies on domestication and avian feather coloration.

Identification and Validation of an EMT-Related LncRNA Signature for HNSCC to Predict Survival and Immune Landscapes.

Long noncoding RNAs (lncRNAs) are increasingly recognized as decisive factors in the progression of head and neck squamous cell carcinoma (HNSCC), and they participate in the epithelial-mesenchymal transformation (EMT) of HNSCC. LncRNAs are closely related to the prognosis of patients with HNSCC; thus, it is essential to identify EMT-related lncRNAs with prognostic value for HNSCC. The coexpression network of EMT-related lncRNAs was constructed using The Cancer Genome Atlas (TCGA). An EMT-related eight-lncRNA-based prognostic signature was constructed using LASSO Cox regression and Cox proportional hazards analyses. Univariate and multivariate analyses and stratified prognosis confirmed that the prognostic signature was an independent predictive factor. Subsequently, we performed immune cell infiltration analysis, gene set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA) pathway enrichment analysis to uncover the potential molecular mechanisms of prognostic differences in the high- and low-risk groups. Next, we discussed the relationship between the prognostic signature and immune checkpoint-related genes, their TIDE scores, and the sensitivity of common chemotherapeutics. Finally, we further verified the expression differences in lncRNAs that were included in our signature via RT-qPCR in eighteen paired tissues. In summary, this prognostic signature provides powerful prognostic biomarkers for HNSCC and could serve as a predictor for the sensitivity of common chemotherapeutics and immunotherapy responses as well as providing a reference for further personalized treatment.

Identification of Candidate Circular RNAs Underlying Intramuscular Fat Content in the Donkey.

Intramuscular fat (IMF) content is a crucial indicator of meat quality. Circular RNAs (circRNAs) are a large class of endogenous RNAs that are involved in many physiological processes. However, the expression and function of circRNA in IMF in the donkey remains unresolved. Here we performed an expression profiling of circRNAs in the donkey longissimus dorsi muscle and identified 12,727 candidate circRNAs. Among these, 70% were derived from the exons of protein genes. Furthermore, a total of 127 differentially expressed (DE) circRNAs were identified in high (H) and low (L) IMF content groups, including 63 upregulated and 64 downregulated circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the host genes of the DE circRNAs showed that the host genes were enriched in lipid metabolism related GO terms (e.g., fatty acid beta-oxidation using acyl-CoA dehydrogenase and MLL3/4 complex), and signaling pathways (e.g., TGF-beta and lysine degradation signaling pathway). Further analyses indicated that 127 DE circRNAs were predicted to potentially interact with miRNAs, leading to the construction of circRNA-miRNA regulatory network. Multiple circRNAs can potentially function as sponges of miRNAs that regulate the differentiation of adipocytes. Our results provide valuable expression profile information for circRNA in the donkey and new insight into the regulatory mechanisms of circRNAs in the regulation of IMF content.

[Effect of dapagliflozin on gene expression of glucose transporter 2 and glucose transporter 4 in kidney of type 2 diabetic rats].

Objective: To investigate the effects of dapagliflozin on the gene expressions of glucose transporter 2 (GLUT2) and glucose transporter 4 (GLUT4) in type 2 diabetic rats. Methods: High fat diet and 40 mg/kg streptozotocin (STZ) were used to establish the rat model of type 2 diabetes mellitus. When the fasting blood glucose (FBG) content was more than or equal to 16.7 mmol/L, the model was established successfully. After successful modeling, the rats were randomly divided into model group (group B, normal saline), dapagliflozin low-dose group (Group C, 0.75 mg/kg), dapagliflozin middle dose group (Group D, 1.5 mg/kg) and dapagliflozin high-dose group (Group E, 3.0 mg/kg), with 6 rats in each group. Six healthy SD rats were selected as normal control group (group A, normal saline). Each group was administrated by gavage once a day for 7 weeks. The body weight, serum FBG, hemoglobin A1c (HbA1c), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured after 7 weeks. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in serum and kidney were measured by enzyme-linked immunosorbent assay (ELISA). HE staining was used to observe the pathological changes of kidney. The protein expressions of GLUT2 and GLUT4 were detected by Western blot. RT-qPCR was used to detect the relative expressions of GLUT2 and GLUT4 mRNA in kidney tissue. Results: Compared with group A, the body weight, SOD, GSH-Px levels of rats in each group were significantly decreased (P＜0.05), while the levels of FBG, HbA1c, BUN, SCR and MDA were significantly increased (P＜0.05), renal pathological damage was serious, the relative expressions of GLUT2, GLUT4 mRNA and protein in renal tissue were significantly decreased (P＜0.05). Compared with group B, the body weight, SOD, GSH-Px levels and the mRNA relative expressions of GLUT2 and GLUT4 in group C, group D and group E were significantly increased (P＜0.05), while the levels of FBG, HbA1c, BUN, SCR and MDA were significantly decreased (P＜0.05). The renal pathological damage in group D and group E was significantly alleviated, and the expressions of GLUT2 and GLUT4 protein in renal tissue were significantly increased (all P＜0.05). Conclusion: Dapagliflozin can alleviate the condition of type 2 diabetic rats and up regulate the expression of GLUT2 and GLUT4 genes in kidney.

Effects of massage treatment combined with topical cactus and aloe on puerperal milk stasis.

AIM: Puerperal milk stasis is one of the most common puerperal complication that directly affects breastfeeding. Massage treatment with topical cactus and aloe for puerperal milk stasis might be a superior treatment, and it does not affect breastfeeding. METHODS: The intervention group was treated with massages with cactus and aloe cold compresses, and the control group was treated with massage treatment or cactus and aloe cold compresses alone. We evaluated the efficacies of the treatments through comparisons of the feeding patterns, hardness, and pain after treatment between the three groups. RESULTS: We found that breastfeeding rates were significantly increased in the massage combine with combined with cactus and aloe cold compress group (P < 0.05 for both). Breast hardness and pain were reduced to greater extents in massage combine with combined with cactus and aloe cold compress group than in the massage or cold compress group (P < 0.05). CONCLUSIONS: Massage treatment with topical cactus and aloe topical effectively improved the pain status, hard lump of puerperal milk stasis and increase breastfeeding rate.