Ye Wang

Objective: To investigate whether the reliability of telesurgery is non-inferior to that of standard local surgery in patients undergoing urological robotic operations. Design: Multicentre, non-inferiority, randomised controlled trial. Setting: Five hospitals in China from December 2023 to June 2024. Participants: Patients scheduled to undergo radical prostatectomy or partial nephrectomy. Interventions: Patients were randomly assigned 1:1 to undergo telesurgery or local surgery. Main outcome measures: The primary outcome was the probability of success of surgery, determined by the medical team on the basis of pre-established criteria. The pre-specified non-inferiority margin was an absolute reduction in probability of 0.1. Thirteen clinical secondary outcomes were associated with the operation and early recovery, and one secondary outcome related to the workload of the medical team. Four technical secondary outcomes for the surgical system were also explored, including network latency, display latency, frame loss during telesurgery, and system malfunction. The participants were followed up at four and six weeks postoperatively for the secondary outcomes of recovery and complications. Results: A total of 72 participants were enrolled in the study and randomised 1:1 to the telesurgery group and the local surgery group for the intention-to-treat set. The median age of patients was 61.0 (interquartile range 57.5-68.0) years in the telesurgery group and 65.0 (56.5-70.0) years in the local surgery group. Telesurgery was not inferior to local surgery in terms of the probability of surgical success in the intention-to-treat population, accounting for clustering by surgeon (success probability difference 0.02 (95% credible interval −0.03 to 0.15) with bayesian posterior probability of 0.99 for non-inferiority). The telesurgery system was stable with a distance from 1000 km to 2800 km, a mean round trip network latency of 20.1-47.5 ms, and frame loss of 0-1.5 per telesurgery. Secondary outcomes, including operative basic data, complications, early recovery, oncological outcome, and medical team workload, did not differ substantially between the two groups. Conclusions: The reliability of telesurgery was non-inferior to that of local robotic surgery according to the non-inferiority margin of a 0.1 reduction in success probability. Trial registration: ChiCTR.org ChiCTR2300077721.

Targeting the dysregulation of essential metal homeostasis represents a rapidly evolving frontier in cancer immunotherapy. The tumor microenvironment (TME) is a complex immunosuppressive ecosystem comprising tumor cells, immune cells, stromal components, extracellular matrix, and diverse cytokines/chemokines, characterized by hypoxia, acidosis, elevated redox stress, and metabolic dysregulation that drive tumor progression and immunotherapy resistance. Crucially, dysregulated homeostasis of essential metals (e.g., Cu, Fe, Zn, Mg, Mn, Ca, Cr, Na, K) pervades the TME, directly promoting tumorigenesis through oncogenic pathway activation and aberrant energy metabolism while facilitating immune evasion, amplifying immunosuppression, and undermining cancer immunotherapies. In response, recent strategies have focused on leveraging metalloimmunology to reprogram the TME via: (1) activation of innate/adaptive immunity, (2) disruption of tumor metabolism, (3) induction of programmed cell death, and (4) triggering of immunogenic cell death (ICD). These approaches synergize with existing immunotherapies to enhance efficacy, aided by nanotechnology-enabled precision delivery of metal-based agents. In conclusion, by mastering the intricate interplay between metal ions and the immunosuppressive TME, these strategies hold immense potential to remodel the TME, reinvigorate anti-tumor immunity, and ultimately enhance the efficacy of next-generation cancer immunotherapies. This review presents metalloimmunology as an integrative paradigm connecting metal biology, tumor immunology, and nanotechnology, providing a transformative outlook for immunotherapy.

House dust mites (HDM) can cause DNA double-strand breaks in the lungs of asthmatic patients. However, the molecular mechanisms driving DNA damage and repair in HDM-induced asthma are yet to be elucidated. Thus, in this study, HDM treatment was applied to BEAS-2B cells and mice to mimic the pathological process of asthma in vitro and in vivo, respectively. γ-H2AX foci and expression were measured by immunofluorescence staining and Western blot, respectively. The levels of IL-4, IL-6, IL-13, and TNF-α were measured using ELISA. The expression of USP25 and BARD1 was measured by reverse transcription quantitative PCR and Western blot. Co-immunoprecipitation and ubiquitination assays were employed to detect the relationship between USP25 and BARD1. As per the results, it was found that the deubiquitylating enzyme USP25 repressed HDM-induced DNA damage and the production of proinflammatory cytokines, including TNF-α, IL-4, IL-8, and IL-13, in BEAS-2B cells; in contrast, the depletion of USP25 led to the opposite effects. USP25-mediated inhibition of DNA damage and inflammation was facilitated by the stabilizing protein BARD1, which is a tumor suppressor that principally functions by promoting DNA repair and replication in BEAS-2B cells. Furthermore, USP25 was found to robustly augment BARD1 protein abundance and prevent HDM-induced DNA damage and inflammation in vivo. Taken together, these results suggest a novel mechanism contributing to DNA damage and repair in HDM-induced asthma and that selectively modulating this pathway could lead to a novel therapeutic approach for controlling and managing asthma due to HDM exposure.

Background. Ovarian cancer is the most fatal gynecological malignancy. Owing to its insidious onset, rapid development, and poor prognosis, ovarian cancer is the fifth most common cause of death in women. Although immunotherapy-related drugs, such as Olaparib, can alleviate ovarian cancer progression, there are no remarkable breakthroughs for its effective treatment. It is considered that the transformation of normal cells to cancerous ones involves “recoding” of certain metabolic pathways. Diacylglycerol O-acyltransferase 1 (DGAT1) can synthesize triglycerides by transferring acyl-CoA to diacylglycerol, which plays a key role in lipid synthesis. However, the role of DGAT1 in ovarian cancer is not yet elucidated. Materials and Methods. We analyzed the correlation between DGAT1 and ovarian cancer staging, grading, vascular invasion, and prognosis by collating the information of ovarian cancer specimens from The Cancer Genome Atlas (TCGA) database. Furthermore, the effects of DGAT1 expression on proliferation, migration, invasion, and tumor growth were studied using ovarian cancer cell lines. GSEA was used to analyze the KEGG pathways and biological function enriched because of DGAT1 expression in ovarian cancer. Results. The expression of DGAT1 was elevated in advanced ( ), poorly differentiated ( ), and vascular invaded ( ) ovarian cancer specimens. Prognosis among patients with high expression of DGAT1 was poor. After DGAT1 expression was interfered, proliferation, migration, invasion, colony forming, and tumor growth of ovarian cancer cells were inhibited. In addition, GSEA showed that DGAT1 may be involved in the immune process. Conclusion. DGAT1 expression is associated with the clinical phenotype of ovarian cancer. We suggest that DGAT1 has potential implications in the treatment of ovarian cancer.

Evidence from clinical cases indicates an association between the low success rate of in vitro fertilization (IVF) and ovarian injury due to previous methotrexate (MTX) administration. Therefore, it is necessary to develop and propose reasonable clinical drug guidelines to improve the quality of oocytes and the development of embryos before pregnancy. In this study, we established a mouse model with previous MTX exposure to validate the effects of MTX on reproductive function in female mice. We observed that MTX administration could result in a decrease in the success rate of fertilization and an aberrant embryonic development in both natural fertilization and IVF, even after completion of five to six ovulation cycles after MTX withdrawal. Further research revealed senescence and apoptosis of follicular granulosa cells (GCs), accompanied by arrested follicle development and aberrant estradiol and anti‐Mullerian hormone levels. Supportive evidence indicated that MTX administration induced senescence and apoptosis of human GCs in vitro, and the effects were consistent with the high levels of p21, p53, and oxidative stress. We further demonstrated that folic acid (FA) could improve oocyte function and embryonic development in vivo and in vitro by protecting GCs against apoptosis and senescence. Based on these findings, we propose the implementation of extended intervals between MTX exposure and conception or IVF and recommend FA as a special dietary supplement during this interval period; however, prospective inquiry in humans is necessary to further understand the relationship between MTX and FA recovery.

BackgroundNon-obstructive azoospermia (NOA) in males is a disease commonly associated with infertility, and is characterized by a disorder in spermogenesis, which may be caused by chromosomal abnormalities, orchitis, or chemical therapy. Spermogenesis is a process tightly regulated by precise gene expression patterns. However, the key genes and signaling pathways contributing to NOA remain unclear.MethodsIn this study, weighted gene co-expression network analysis was performed to identify NOA-associated gene clusters, and combined with the KEGG pathway assay and biological research.ResultsOur results revealed that the cellular senescence signaling pathway may play important roles in NOA. Indeed, cellular senescence is a complex biological process, often associated with disorder in cellular function. Using different expression genes (DEGs), the core, NOA-associated gene set in the cellular senescence pathway was identified; it contained SMAD2, which was upregulated, and HIPK4, which was downregulated. Consequently, the database was divided based on the expression levels of SMAD2 and HIPK4, and the GSEA (Gene Set Enrichment Analysis) assay, as well as the GO and KEGG assays of genes co-expressing with SMAD2 and HIPK4, showed that these two genes may take part in the regulation of cellular senescence, sperm differentiation and development, and energy metabolism.ConclusionsThe two genes, SMAD2 and HIPK4, took part in the regulation of senescence, and indicated that the cellular senescence of sertoli cells may play important roles in the NOA. This research can help us understand the mechanisms underlying NOA, and suggest anti-senescence therapeutic approaches that target these associated genes, especially SMAD2 and HIPK4.

Due to the wide use of nuclear energy, nuclear radiation threat is increasing day by day. However, methods for protection against nuclear radiation are limited and not effective. Therefore, it is necessary to develop an effective method for protection and therapy against injury caused by radiation. According to the law of biological evolution, one of the most primitive eukaryotes, Paramecium , could be tolerant to ionizing radiations, in a way similar to or better than Ramazzottius varieornatus and Bdelloids rotifer . Therefore, in the present study, the anti-radiation effects of Paramecium were explored, which could be applicable to human beings. Paramecium was found to be tolerant to ⁶⁰ Co γ rays, and its half lethal dose (LD50) was approximately 3000 Gy, which is 60 times more than that of human beings. The GSPATT00021409001 and GSPATT00016349001 genes were significantly up-regulated, which might play a role in DNA binding and nuclear transport, and thus, could function in DNA protection or repair. The biological function of the two genes and their effects in humans need to be explored in future studies.