In swine production, stress is a common encounter that leads to serious bacterial infection and adverse effects on growth performance. Though antibiotics have been frequently used to control pathogen spread, sustained negative impacts from antibiotics have been found to affect intestinal integrity and the immune system. Multiple nutritional strategies have shown potential to counteract stress and replace antibiotics, including functional amino acids, low protein diet, plant extracts, organic acids, prebiotics, probiotics, minerals and vitamins. These additives relieve the stress response in swine via different mechanisms and signal transduction pathways. Based on the overview of signaling pathways and stress models, this review highlights the potential of nutritional strategies in swine for preventing or treating stress-related health problems. For wider application in the pig industry, the dose ranges measured require for further validation in different physiological contexts and formulations. In the future, microfluid devices and novel stress models are expected to enhance the efficiency of screening for new anti-stress candidates.

Objective: In recent years, the anti-programmed cell death protein-1 and its ligand (PD-1/PD-L1) or combination therapies have been recommended as an alternative emerging choice of treatment for oncology patients. However, the efficacy and adverse events of different combination strategies for the treatment of tumors remain controversial. Methods: PubMed, Embase, Cochrane Library, the American Society of Clinical Oncology (ASCO), and the European Society of Medicine Oncology (ESMO) were searched from database inception until 16 February 2022. The endpoints of objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were analyzed from different treatment schemes and tumor types. The protocol was registered in PROSPERO (CRD42022328927). Results: This meta-analysis included forty-eight eligible studies. Combination therapy has improved ORR (RR = 1.40, p < 0.001), DCR (RR = 1.22, p < 0.001), and PFS (the median survival ratio (MSR) was estimated to be 1.475 p < 0.001) compared to anti-PD-1/PD-L1 but had no significant benefit on OS (MSR was estimated to be 1.086 p = 0.117). Besides, combination treatment strategies are more toxic in any grade AEs (RR = 1.13, p < 0.001) and grade 3–5 AEs (RR = 1.81, p < 0.001). Conclusions: Treatment with PD-1/PD-L1 inhibitors in combination with other antitumor therapies improve patients’ ORR, DCR, and PFS compared to anti-PD-1/PD-L1. However, it is regrettable that there is no benefit to OS and an increased risk of AEs in combinatorial therapies.

Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus remains a clinical challenge due to limited therapies and rising antifungal resistance. Here, we evaluated nitroxoline (NTX), an FDA-approved 8-hydroxyquinoline derivative, for its antifungal potential and mechanism of action. NTX exhibited potent in vitro activity against 64 clinical isolates and the AF293 reference strain, delaying conidial maturation and significantly improving survival, reducing pulmonary fungal burden, and alleviating lung inflammation and hyphal invasion in an IPA mouse model. Transcriptomic analysis revealed marked downregulation of the high-affinity Cu transporter ctrC and superoxide dismutase sodB , disrupting the copper homeostasis-oxidative stress axis. Copper supplementation restored hyphal growth and intracellular ROS levels, supporting a mechanism of copper deprivation-induced oxidative stress. These findings demonstrate that NTX exerts strong anti- A . fumigatus effects in vitro and in vivo by perturbing copper homeostasis and inducing oxidative stress, highlighting its unique antifungal potential and providing a conceptual basis for metal-targeted therapeutic strategies against IPA and drug-resistant fungal infections.