Contributions of T Cell Signaling for Wound Healing.

It has long been known that T cells participate in wound healing, however, it is still enigmatic about the landscape of the signaling derived from T cells in the process of wound healing. With the advantages of scRNA-seq, in combination of immunofluorescent imaging, we identified activated T cells, cytotoxic T cells (CTLs), exhausting T cells and Tregs existing in inflammation phase of wound healing. Further analysis revealed each T cell population possess distinguished signals contributed to wound healing, some are critical for improving the wound healing quality. Besides, this study discovered and validated the exhistance of exhausting T cells among the T cells accumulated in skin duing wound healing, and the molecular mechanism(s) and contribution of exhausting T cells to wound healing deserves extensive studies in the future.

The up-regulation of PD-L1 during boningmycin-induced senescence in human cancer cells depends on the activation of the JAK/STAT signaling pathway mediated by SASP.

Therapy-induced senescence can regulate both the innate and adaptive immune systems, thereby affecting therapeutic efficacy. Bleomycin is a major component of combined chemotherapy regimens, utilized for the treatment of multiple tumors, whereas pulmonary toxicity severely restricts its clinical benefits. As a member of the bleomycin family, boningmycin (BON) exhibits potent anticancer activity with minimal pulmonary toxicity, making it a potential alternative to bleomycin. Low concentrations of BON can induce senescence, but the impact of BON-induced senescence on anticancer immunity remains unclear. This study investigates the effects of BON-induced senescence on PD-L1 expression and the underlying mechanisms in human cancer cells. Firstly, the elevation of PD-L1 protein during BON-induced senescence was confirmed by a senescence ß-galactosidase staining assay, detection of the senescence-associated secretory phenotype (SASP), western blot and flow cytometry in human lung cancer NCI-H460 cells and breast cancer MDA-MB-231 cells. Subsequently, it was shown that the increase in PD-L1 protein is mediated by SASP, as evidenced by the use of conditional media, knockdown of cyclic GMP-AMP synthase and inhibition of stimulator of interferon genes. Ultimately, it was demonstrated that SASP-mediated PD-L1 up-regulation is dependent on the activation of the JAK/STAT pathway through the use of specific inhibitors and siRNAs. These findings clarify the impact of BON-induced senescence on PD-L1 expression and may contribute to the optimization of the therapeutic efficacy of bleomycin-related compounds and the clinical transformation of BON.

Effect of liver transplants with retrograde reperfusion on early postoperative recovery of liver function and its risk factors.

BACKGROUND: The purpose of this study was to investigate effect of liver Transplants (LT) with retrograde reperfusion on early postoperative recovery of liver function and its risk factors. METHODS: We conducted a retrospective analysis of clinical data from 136 liver transplantation (LT) patients at the 900th Hospital of the Chinese People's Liberation Army Joint Support Army, covering the period from January 2015 to January 2021. All participants provided informed consent, adhering to medical ethics guidelines. Patients were stratified into two groups based on the liver perfusion technique used: retrograde reperfusion (RTR, n = 108) and initial portal reperfusion (IPR, n = 28). Our study focused on a subset of 23 patients from each group to compare postoperative liver function recovery. The final analysis included 86 RTR and 28 IPR cases after excluding 8 RTR patients who underwent initial hepatic artery reperfusion and 14 who received simultaneous hepatic artery and portal vein reperfusion. Further subdivision within the RTR group identified 19 patients with early hepatic allograft dysfunction (EAD) and 67 without, allowing for an assessment of the influence of preoperative and intraoperative parameters, as well as perfusion methods, on EAD incidence post-LT. RESULTS: Alanine aminotransferase (ALT) was 329 (211 ~ 548) and 176 (98 ~ 282) U/L on the 3rd and 7th day after RTR, respectively, which was significantly lower than 451 (288 ~ 918) and 251 (147 ~ 430) U/L in the IPR group (Z =-1.979, -2.299, P = 0.048, 0.021). Aspartate aminotransferase (AST) on postoperative days 3, 5, and 7 was 252 (193, 522), 105 (79, 163), and 93 (41, 135) U/L in the RTR group, respectively; it was also significantly lower than 328 (251, 724), 179 (129, 306), and 150 (91, 200)U/L in the IPR group (Z=-2.212, -3.221, -2.979; P = 0.027, 0.001, 0.003). Logistic regression analysis showed that MELD score was an independent risk factor for EAD after LT. CONCLUSION: RTR LT is more favorable for patients' early postoperative liver function recovery. For patients undergoing LT for RTR, preoperative MELD score was an independent risk factor for their postoperative development of EAD.

Exploring the role of CD8+ T cells in clear renal cell carcinoma metastasis.

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 75-80% of all patients with renal cell carcinoma. Despite its prevalence, little is known regarding the key components involved in ccRCC metastasis. In this study, scRNA-seq analysis was employed to classify CD8+ T cells into four sub-clusters based on their genetic profiles and immunofluorescence experiments were used to validate two key clusters. Through gene set enrichment analysis, these newly identified sub-clusters were found to exhibit distinct biological characteristics. Notably, TYMP, TOP2A, CHI3L2, CDKN3, CENPM, and RZH2 were highly expressed in these sub-clusters, indicating a correlation with poor prognosis. Among these sub-clusters, CD8+ T cells (MT-ND4) were identified as potentially playing a critical role in mediating ccRCC metastasis. These results contribute to our understanding of CD8+ T cell heterogeneity in ccRCC and shed light on the mechanisms underlying the loss of immune response against cancer.

Physiological and molecular mechanism of Populus pseudo-cathayana × Populus deltoides response to Hyphantria cunea.

Populus pseudo-cathayana × Populus deltoides is a crucial artificial forest tree species in Northeast China. The presence of the fall webworm (Hyphantria cunea) poses a significant threat to these poplar trees, causing substantial economic and ecological damage. This study conducted an insect-feeding experiment with fall webworm on P. pseudo-cathayana × P. deltoides, examining poplar's physiological indicators, transcriptome, and metabolome under different lengths of feeding times. Results revealed significant differences in phenylalanine ammonia-lyase activity, total phenolic content, and flavonoids at different feeding durations. Transcriptomic analysis identified numerous differentially expressed genes, including AP2/ERF, MYB, and WRKY transcription factor families exhibiting the highest expression variations. Differential metabolite analysis highlighted flavonoids and phenolic acid compounds of poplar's leaves as the most abundant in our insect-feeding experiment. Enrichment analysis revealed significant enrichment in the plant hormone signal transduction and flavonoid biosynthetic pathways. The contents of jasmonic acid and jasmonoyl-L-isoleucine increased with prolonged fall webworm feeding. Furthermore, the accumulation of dihydrokaempferol, catechin, kaempferol, and naringenin in the flavonoid biosynthesis pathway varied significantly among different samples, suggesting their crucial role in response to pest infestation. These findings provide novel insights into how poplar responds to fall webworm infestation.

Comparison of Sleeve Gastrectomy with Loop Duodenojejunal Bypass Versus One Anastomosis Gastric Bypass for Type 2 Diabetes: The Role of Pylorus Preservation.

BACKGROUND: One anastomosis gastric bypass (OAGB) is recognized as a standard procedure in metabolic surgery. However, concerns about postoperative bile reflux and nutritional risks are prevalent. Comparatively, sleeve gastrectomy with loop duodenojejunal bypass (SG + LoopDJB) bypasses an equivalent length of the foregut as OAGB while maintaining pyloric function. The role of pylorus function remains to be further elucidated regarding these metabolic procedures' therapeutic outcomes and side effects. METHOD: A retrospective study was conducted in our center to compare the surgical safety and 1-year outcomes of OAGB and SG + LoopDJB regarding type 2 diabetes mellitus (T2DM) remission, weight loss, gastrointestinal disorders, and nutritional status in T2DM patients matched by gender, age, and BMI. RESULTS: The baseline characteristics were comparable between groups. Compared with OAGB, SG + LoopDJB had longer operative time and length of stay (LOS) but similar major postoperative complications. At 1-year follow-up, OAGB has similar diabetes remission (both 91.9%), weight loss effect (28.1 ± 7.1% vs. 30.2 ± 7.0% for %TWL), and lipidemia improvement to SG + LoopDJB (P > 0.05). However, OAGB presented a higher incidence of hypoalbuminemia (11.9% vs. 2.4%, P = 0.026) but a low incidence of gastroesophageal reflux disease (GERD) symptoms (9.5% vs. 26.2%, P = 0.046) than SG + LoopDJB. There was no statistical difference regarding other gastrointestinal disorders and nutritional deficiencies between groups. CONCLUSION: Both OAGB and SG + LoopDJB show comparable, favorable outcomes in weight loss, T2DM remission, and lipidemia improvement at the 1-year follow-up. Pylorus preservation, while increasing surgical difficulty and the risk of de novo GERD, may reduce the risk of postoperative hypoalbuminemia.

Identification and functional analysis of the DOF gene family in Populus simonii: implications for development and stress response.

Background: Populus simonii, a notable native tree species in northern China, demonstrates impressive resistance to stress, broad adaptability, and exceptional hybridization potential. DOF family is a class of specific transcription factors that only exist in plants, widely participating in plant growth and development, and also playing an important role in abiotic stress response. To date, there have been no reported studies on the DOF gene family in P. simonii, and the expression levels of this gene family in different tissues of poplar, as well as its expression patterns under cold, heat, and other stress conditions, remain unclear. Methods: In this study, DOF gene family were identified from the P. simonii genome, and various bioinformatics data on the DOF gene family, gene structure, gene distribution, promoters and regulatory networks were analyzed. Quantitative real time PCR technology was used to verify the expression patterns of the DOF gene family in different poplar tissues. Results: This research initially pinpointed 41 PSDOF genes in P. simonii genome. The chromosomal localization results revealed that the PSDOF genes is unevenly distributed among 19 chromosomes, with the highest number of genes located on chromosomes 4, 5, and 11. A phylogenetic tree was constructed based on the homology between Arabidopsis thaliana and P. simonii, dividing the 41 PSDOF genes into seven subgroups. The expression patterns of PSDOF genes indicated that specific genes are consistently upregulated in various tissues and under different stress conditions, suggesting their pivotal involvement in both plant development and response to stress. Notably, PSDOF35 and PSDOF28 serve as pivotal hubs in the interaction network, playing a unique role in coordinating with other genes within the family. Conclusion: The analysis enhances our comprehension of the functions of the DOF gene family in tissue development and stress responses within P. simonii. These findings provide a foundation for future exploration into the biological roles of DOF gene family.

O-GlcNAcylation promotes the progression of nonalcoholic fatty liver disease by upregulating the expression and function of CD36.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) and its progressive variant, nonalcoholic steatohepatitis (NASH), constitute a burgeoning worldwide epidemic with no FDA-approved pharmacotherapies. The multifunctional immunometabolic receptor, fatty acid translocase CD36 (CD36), plays an important role in the progression of hepatic steatosis. O-GlcNAcylation is a crucial posttranslational modification that mediates the distribution and function of CD36, but its involvement in NAFLD remains poorly understood. METHODS: O-GlcNAcylation and CD36 expression were evaluated in human liver tissues obtained from NASH patients and normal control. Mice with hepatocyte-specific CD36 knockout were administered adeno-associated viral vectors expressing wild-type CD36 (WT-CD36) or CD36 O-GlcNAcylation site mutants (S468A&T470A-CD36) and were provided with a high-fat/high-cholesterol (HFHC) diet for 3 months. RT-qPCR analysis, immunoblotting, dual-luciferase reporter assays, chromatin immunoprecipitation, and coimmunoprecipitation were performed to explore the mechanisms by which O-GlcNAcylation regulates CD36 expression. Membrane protein extraction, immunofluorescence analysis, site-directed mutagenesis, and fatty acid uptake assays were conducted to elucidate the impact of O-GlcNAcylation on CD36 function. RESULTS: O-GlcNAcylation and CD36 expression were significantly increased in patients with NASH, mouse models of NASH, and palmitic acid-stimulated hepatocytes. Mechanistically, the increase in O-GlcNAcylation facilitated the transcription of CD36 via the NF-κB signalling pathway and stabilized the CD36 protein by inhibiting its ubiquitination, thereby promoting CD36 expression. On the other hand, O-GlcNAcylation facilitated the membrane localization of CD36, fatty acid uptake, and lipid accumulation. However, site-directed mutagenesis of residues S468 and T470 of CD36 reversed these effects. Furthermore, compared with their WT-CD36 counterparts, HFHC-fed S468A&T470A-CD36 mice exhibited decreases in systemic insulin resistance, steatosis severity, inflammation and fibrosis. Pharmacological inhibition of O-GlcNAcylation and CD36 also mitigated the progression of NASH. CONCLUSIONS: O-GlcNAcylation promotes the progression of NAFLD by upregulating CD36 expression and function. Inhibition of CD36 O-GlcNAcylation protects against NASH, highlighting a potentially effective therapeutic approach for individuals with NASH.

FBXO43 promotes cell cycle progression in cancer cells through stabilizing SKP2.

FBXO43 is a member of the FBXO subfamily of F-box proteins, known to be a regulatory hub during meiosis. A body of data showed that FBXO43 is overexpressed in a number of human cancers. However, whether and how FBXO43 affects cell cycle progression and growth of cancer cells remain elusive. In this study, we provide first piece of evidence, showing a pivotal role of FBXO43 in cell cycle progression and growth of cancer cells. Specifically, FBXO43 acts as a positive cell cycle regulator with an oncogenic activity in variety types of human cancer, including non-small cell lung cancer, hepatocellular carcinoma and sarcoma. Mechanistically, FBXO43 interacts with phosphorylated SKP2 induced by AKT1, leading to reduced SKP2 auto-ubiquitylation and subsequent proteasome degradation. Taken together, our study demonstrates that FBXO43 promotes cell cycle progression by stabilizing SKP2, and FBXO43 could serve as a potential anti-cancer target.

The current status and challenges of perioperative management of patients with a BMI of greater than or equal to 50 kg/m 2 undergoing bariatric surgery in China: a multicenter cross-sectional study.

BACKGROUND: Performing bariatric surgery on patients with a BMI of over 50 kg/m 2 is challenging. This study aimed to explore the status and challenges related to the perioperative management of such patients in China. MATERIALS AND METHODS: A prospective survey was designed to investigate the perioperative management of patients with a BMI of greater than or equal to 50 kg/m 2 undergoing bariatric surgery in China. The questionnaire of our survey included general information, preoperative management measures, surgical procedures performed, technical details regarding anaesthesia, and postoperative management measures. A response from only one attending physician per bariatric centre was accepted. RESULTS: Physicians from a total of 101 hospitals responded to the questionnaire, and the questionnaire data from 98 hospitals were complete. These centres had completed a total of 44 702 bariatric surgeries since the launch of such surgery to December 2021. A total of 3280 patients had a BMI exceeding 50 kg/m 2 . The preferred surgical procedures for patients with super obesity were sleeve gastrectomy by 62 centres, Roux-en-Y gastric bypass by 11 centres, sleeve gastrectomy plus jejunojejunal bypass by 19 centres, one anastomosis gastric bypass by 1 centre, and duodenal switch by 1 centre. The most worrying issues were cardiopulmonary failure and difficulty in extubation. 91 centres believed that preoperative weight loss was beneficial. A low-calorie diet was the specific measure mainly implemented, only three centres considered using intragastric balloon placement. Postoperative management measures varied greatly. CONCLUSION: Bariatric surgery has seen rapid development. Chinese physicians show significant differences regarding the perioperative management for patients with a BMI of over 50 kg/m 2 . The perioperative risks of these patients remain relatively high, making further development of clinical pathways is necessary.