As a post-translational modification (PTM) mechanism analogous to ubiquitination, ubiquitin-like (UBL) modification plays a crucial regulatory role in virus-host interactions. With the increasing discovery of UBL modification types, their roles in diverse biological process, including HIV infection, have gained growing attention. Rather than merely serving as anti-HIV defenses or being exploited by the virus, UBLs often exert dual roles by modulating both host restriction factors and viral proteins, thereby impacting key steps of HIV life cycle, immune evasion, and intracellular signaling. This article summarizes recent advances on the contribution of UBLs in regulating HIV replication and host defense, highlighting their indispensable roles in arms races between HIV and host, aiming to provide a theoretical framework for developing novel therapeutic strategies against HIV-1 targeting virus-host interactions.

Natural killer (NK) cells contribute to liver transplant (LTx) rejection. However, the blood-circulating NK-cell dynamics of patients who experience acute rejection (AR) are unclear. Herein, we longitudinally profiled the total NK cells and their subsets, along with the expression of activating and inhibitory receptors in sequential peripheral blood mononuclear cell samples, spanning from before LTx to the first year after LTx of 32 patients with AR and 30 patients under a steady immune status. Before transplantation, patients with AR (rejectors) contained a significantly higher proportion of the immature CD56^brightCD16^– subset and a lower cytolytic CD56^dimCD16⁺ in the total blood-circulating NK cells than patients with steady immunity. Both subsets contained a high NKp30-positive population, and CD56^dimCD16⁺ additionally exhibited a high NKp46-positive ratio. The NKp30-positive ratio in CD56^dimCD16⁺ subset showed the most prominent AR predictive ability before LTx and was an independent risk factor of LTx AR. After transplantation, the blood-circulating NK cells in rejectors maintained a higher CD56^brightCD16⁻ and lower CD56^dimCD16⁺ composition than the controls throughout the first year after LTx. Moreover, both subsets maintained a high NKp30-positive ratio, and CD56^dimCD16⁺ retained a high NKp46-positive ratio. The blood-circulating NK cell subset composition was consistent during AR, while the expressions of NKp30 and NKp46 were augmented. Collectively, a more immature CD56^brightCD16⁻ subset composition and an activated phenotype of high NKp30 expression were the general properties of blood-circulating NK cells in rejected LTx recipients, and the NKp30-positive ratio in CD56^dimCD16⁺ NK subset before LTx possessed AR predictive potential.

Objective: To compare the efficacy and safety of radical extrahepatic cyst excision including the intrapancreatic bile duct (REC) and subtotal extrahepatic cyst excision preserving the intrapancreatic bile duct (SEC) in treating Todani type I congenital bile duct dilation (CBD) with intrapancreatic bile duct involvement (I-IPBD). Background: The application of REC and SEC in I-IPBD remains debated. Methods: The multicenter study recruited I-IPBDs who underwent REC or SEC from 5 centers between 2006 and 2024. The primary endpoint was occurrence of long-term complications, including recurrent cholangitis, pancreatitis, and intrapancreatic bile duct stones. The secondary outcomes included readmission, reoperation, life quality assessed by Mayo score, carcinogenesis, and perioperative complications categorized as overall, severe, pancreas-related, and severe pancreas-related. Results: 355 I-IPBDs were included and divided into the REC group (175 cases) and SEC (180 cases) from 722 type I CBDs. The REC group demonstrated better long-term complication-free survival compared to SEC group (log-rank P <0.001; HR=0.08, 95%CI: 0.04-0.15, P <0.001). The REC group had lower rates of readmission, reoperation, and carcinogenesis, and achieved a superior Mayo score (P 0.05). Furthermore, subgroup analysis by age demonstrated similar trends in primary and secondary outcomes compared to the overall analysis. Conclusions: REC was an effective and safe surgical approach for I-IPBD compared with SEC, thus it should be recommended routinely for these patients.

T cells are key mediators of alloresponse during liver transplantation (LTx). However, the dynamics of donor-reactive T-cell clones in peripheral blood during a clinical T-cell–mediated rejection (TCMR) episode remain unknown. Here, we collected serial peripheral blood mononuclear cell samples spanning from pre-LTx to 1 year after LTx and available biopsies during the TCMR episodes from 26 rejecting patients, and serial peripheral blood mononuclear cell samples were collected from 96 nonrejectors. Immunophenotypic and repertoire analyses were integrated on T cells from rejectors, and they were longitudinally compared to nonrejected patients. Donor-reactive T-cell clone was identified and tracked by cross-matching with the mappable donor-reactive T-cell receptor repertoire of each donor-recipient pair in 9 rejectors and 5 nonrejectors. Before transplantation, the naive T-cell percentage and T-cell receptor repertoire diversity of rejectors was comparable to that of healthy control, but it was reduced in nonrejectors. After transplantation, the naïve T-cell percentages decreased, and T-cell receptor repertoires were skewed in rejectors; the phenomenon was not observed in nonrejectors. Alloreactive clones increased in proportion in the peripheral blood of rejectors before TCMR for weeks. The increase was accompanied by the naïve T-cell decline and memory T-cell increase and acquired an activated phenotype. Intragraft alloreactive clone tracking in pre-LTx and post-LTx peripheral blood mononuclear cell samples revealed that the pretransplant naïve T cells were significant contributors to the donor-reactive clones, and they temporarily increased in proportion and subsequently reduced in blood at the beginning of TCMR. Together, our findings offer an insight into the dynamic and origin of alloreactive T cells in clinical LTx TCMR cases and may facilitate disease prediction and management.