NIR-responsive CN-Pt-GEM hydrogel induces necroptosis and immunotherapeutic responses prevent postoperative recurrence and wound infection in lung carcinoma.

BACKGROUND: Cancer recurrence following surgical resection is a major cause of treatment failure. Finding effective methods to prevent postoperative recurrence and wound infection is an important component of successful surgery. With the development of new nanotechnology, more treatment options have been provided for postoperative adjuvant therapy. This study presents an innovative hydrogel system that stimulates tumoricidal immunity after surgical resection of non-small cell lung cancer (NSCLC) and prevents cancer relapse. RESULTS: The hydrogel system is based on the excellent photothermal conversion performance of single-atom platinum (CN-Pt) along with the delivery and release of the chemotherapy drug, gemcitabine (GEM). The system is coated onto the wound surface after tumor removal with subsequent near-infrared (NIR) photothermal therapy, which efficiently induces necroptosis of residual cancer cells, amplifies the levels of damage-associated molecular patterns (DAMPs), and increases the number of M1 macrophages. The significantly higher levels of phagocytic macrophages enhance tumor immunogenicity and sensitize cancer cells to CD8 + T-cell immunity to control postoperative recurrence, which has been verified using an animal model of postoperative lung cancer recurrence. The CN-Pt-GEM-hydrogel with NIR can also inhibit postoperative wound infection. CONCLUSIONS: These findings introduce an alternative strategy for supplementing antitumor immunity in patients undergoing resection of NSCLC tumors. The CN-Pt-GEM-hydrogel with the NIR system also exhibits good biosafety and may be adaptable for clinical application in relation to tumor resection surgery, wound tissue filling, infection prevention, and recurrence prevention.

Transjugular intrahepatic portosystemic shunt for esophagogastric variceal bleeding in patients with hepatocellular carcinoma and portal vein tumor thrombus.

BACKGROUND: Whether hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) and acute esophagogastric variceal bleeding (EGVB) can improve the success rate of endoscopic hemostasis and overall survival (OS) from transjugular intrahepatic portosystemic shunt (TIPS) remains controversial. AIM: To compare the clinical outcomes between TIPS and standard treatment for such HCC patients. METHODS: This monocenter, retrospective cohort study included patients diagnosed as HCC with PVTT and upper gastrointestinal bleeding. Patients were grouped by the treatment (TIPS or standard conservative treatment). The success rate of endoscopic hemostasis, OS, rebleeding rates, and main causes of death were analyzed. RESULTS: Between July 2015 and September 2021, a total of 77 patients (29 with TIPS and 48 with standard treatment) were included. The success rate of endoscopic hemostasis was 96.6% in the TIPS group and 95.8% in the standard treatment group. All the 29 patients in TIPS group successful underwent TIPS procedure and had a better OS compared with standard treatment within the first 160 days after treatment (68 days vs 43 days, P = 0.022), but shorter OS after 160 days (298 days vs 472 days, P = 0.022). Cheng's Classification of PVTT, total bilirubin and Child-Pugh class were independently negative associated with OS (all P < 0.05). The main causes of death were liver failure or hepatic encephalopathy (75.9%) in the TIPS group and rebleeding (68.8%) in the standard treatment. CONCLUSION: TIPS could reduce the risk of early death due to rebleeding and prolong short-term survival in HCC patients with PVTT and acute EGVB, which deserves further investigation.

Robust one-tube Ω-PCR strategy accelerates precise sequence modification of plasmids for functional genomics.

Functional genomics requires vector construction for protein expression and functional characterization of target genes; therefore, a simple, flexible and low-cost molecular manipulation strategy will be highly advantageous for genomics approaches. Here, we describe a Ω-PCR strategy that enables multiple types of sequence modification, including precise insertion, deletion and substitution, in any position of a circular plasmid. Ω-PCR is based on an overlap extension site-directed mutagenesis technique, and is named for its characteristic Ω-shaped secondary structure during PCR. Ω-PCR can be performed either in two steps, or in one tube in combination with exonuclease I treatment. These strategies have wide applications for protein engineering, gene function analysis and in vitro gene splicing.

The Fungal Effector Avr-Pita Suppresses Innate Immunity by Increasing COX Activity in Rice Mitochondria.

BACKGROUND: Avr-Pita was the first effector identified in the blast fungus (Magnaporthe oryzae)-rice (Oryza sativa) pathosystem. However, the molecular mechanism underlying its effects on the host plant has remained a long-standing mystery. RESULTS: Here, we report that ectopically expressing Avr-Pita in rice enhances susceptibility to M. oryzae and suppresses pathogen-associated molecular pattern (PAMP)-triggered defense responses. Avr-Pita targets the host mitochondria and interacts with the cytochrome c oxidase (COX) assembly protein OsCOX11, a key regulator of mitochondrial reactive oxygen species (ROS) metabolism in rice. Overexpressing Avr-Pita or OsCOX11 increased COX activity and decreased ROS accumulation triggered by the fungal PAMP chitin. OsCOX11-overexpressing plants showed increased susceptibility to M. oryzae, whereas OsCOX11-knockdown plants showed resistance to M. oryzae. CONCLUSIONS: Taken together, these findings suggest that the fungal pathogen M. oryzae delivers the effector Avr-Pita to the host plant, where it enhances COX activity thus decreasing ROS accumulation. Therefore, this effector suppresses host innate immunity by perturbing ROS metabolism in the mitochondria.