Antibiotic prophylaxis with piperacillin-tazobactam reduces organ/space surgical site infection after pancreaticoduodenectomy: a retrospective and propensity score-matched analysis.

BACKGROUND: The occurrence of surgical site infection (SSI) after pancreaticoduodenectomy (PD) is still relatively high. The aim of this retrospective study is to evaluate the efficacy of piperacillin-tazobactam as perioperative prophylactic antibiotic on organ/space SSI for patients underwent PD. METHODS: Four hundred seven consecutive patients who underwent PD between January 2018 and December 2022 were enrolled and analyzed retrospectively. The univariate and multivariate analysis were used to identify independent risk factors of organ/space SSI. Postoperative complications were compared between the two groups according to the use of prophylactic antibiotics by a ratio of 1:1 propensity score-matched (PSM) analysis. RESULTS: Based on perioperative prophylactic antibiotic use, all 407 patients were divided into the ceftriaxone group (n = 192, 47.2%) and piperacillin-tazobactam group (n = 215, 52.8%). The rate of organ/space SSI was 31.2% with the choice of perioperative antibiotics (OR = 2.837, 95%CI = 1.802-4.465, P < 0.01) as one of independent risk factors. After PSM, there were similar baseline characteristics among the groups. Meanwhile, the piperacillin-tazobactam group had a significant lower rate of organ/space SSI compared to the ceftriaxone group both before and after PSM(P < 0.05). CONCLUSIONS: The adoption of piperacillin-tazobactam as perioperative prophylaxis for patients underwent PD reduced organ/space SSI significantly.

Evolution of catalyst design for controlled synthesis of chiral single-walled carbon nanotubes.

Single-walled carbon nanotubes (SWCNTs) possess superb properties originating from their unique chiral structures. However, accurately controlling the structure of SWCNTs remains challenging due to the structural similarities of their chiral structures, which hinders their widespread application in various fields, particularly in electronics. In recent years, much effort has been devoted to preparing single chiral SWCNTs by adopting three constructive strategies, including growth condition control for structurally unstable liquid catalysts, employing stable solid catalyst design, and pre-synthesis of carbon seeds with a well-defined shape. This review comprehensively discusses the state-of-the-art developments in these approaches as well as their advantages and disadvantages. Moreover, insights into the key challenges and future directions are provided for acquiring chirally pure SWCNTs.

Loss of Claudin-1 incurred by DNMT aberration promotes pancreatic cancer progression.

Pancreatic cancer (PC) is one of the most malignant and deadly tumors of digestive system with complex etiology and pathogenesis. Dysregulations of oncogenes and tumor suppressors due to epigenetic modifications causally affect tumorogenesis; however the key tumor suppressors and their regulations in PC are only partially defined. In this study, we found that Claudin-1 (encoded by CLDN1 gene) was significantly suppressed in PC that correlated with a poor clinical prognosis. Claudin-1 knockdown enhanced PC cell proliferation, migration, and stemness. Pancreatic specific Cldn1 knockout in KPC (LSLKrasG12D/Pdx1-Cre/Trp53R172H+) and KC (LSLKrasG12D/Pdx1-Cre) mice reduced mouse survival, promoted acinar-to-ductal metaplasia (ADM) process, and accelerated the development of pancreatic intraepithelial neoplasia (PanIN) and PC. Further investigation revealed that Claudin-1 suppression was mainly caused by aberrant DNA methylatransferase 1 (DNMT1) and DNMT3A elevations and the resultant CLDN1 promoter hypermethylation, as a DNMT specific inhibitor SGI-1027 effectively reversed the Claudin-1 suppression and inhibited PC progression both in vitro and in vivo in a Claudin-1 preservation-dependent manner. Together, our data suggest that Claudin-1 functions as a tumor suppressor in PC and its epigenetic suppression due to DNMT aberrations is a crucial event that promotes PC development and progression.

DNA Methylation-Mediated GPX4 Transcriptional Repression and Osteoblast Ferroptosis Promote Titanium Particle-Induced Osteolysis.

Metal wear particles generated by the movement of joint prostheses inevitably lead to aseptic osteolytic damage and ultimately prosthesis loosening, which are aggravated by various types of regulated cell death of bone. Nevertheless, the exact cellular nature and regulatory network underlying osteoferroptosis are poorly understood. Here, we report that titanium particles (TP) induced severe peri-implant osteolysis and ferroptotic changes with concomitant transcriptional repression of a key anti-ferroptosis factor, GPX4, in a mouse model of calvarial osteolysis. GPX4 repression was accompanied by an increase in DNA methyltransferases (DNMTs) 1/3a/3b and hypermethylation of the Gpx4 promoter, which were partly mediated by the transcriptional regulator/co-repressor KLF5 and NCoR. Conversely, treatment with SGI-1027, a DNMT-specific inhibitor, resulted in marked reversal of Gpx4 promoter hypermethylation and GPX4 repression, as well as improvement in ferroptotic osteolysis to a similar extent as with a ferroptosis inhibitor, liproxstatin-1. This suggests that epigenetic GPX4 repression and ferroptosis caused by the increase of DNMT1/3a/3b have a causal influence on TP-induced osteolysis. In cultured primary osteoblasts and osteoclasts, GPX4 repression and ferroptotic changes were observed primarily in osteoblasts that were alleviated by SGI-1027 in a GPX4 inactivation-sensitive manner. Furthermore, we developed a mouse strain with Gpx4 haplodeficiency in osteoblasts (Gpx4 Ob+/-) that exhibited worsened ferroptotic osteolysis in control and TP-treated calvaria and largely abolished the anti-ferroptosis and osteoprotective effects of SGI-1027. Taken together, our results demonstrate that DNMT1/3a/3b elevation, resulting GPX4 repression, and osteoblastic ferroptosis form a critical epigenetic pathway that significantly contributes to TP-induced osteolysis, and that targeting DNMT aberration and the associated osteoferroptosis could be a potential strategy to prevent or slow down prosthesis-related osteolytic complications.